The mRNA translation initiation factor eIF4G1 controls mitochondrial oxidative phosphorylation, axonal morphogenesis, and memory.
mRNA translation initiation plays a critical role in learning and memory. The eIF4F complex, composed of the cap-binding protein eIF4E, ATP-dependent RNA helicase eIF4A, and scaffolding protein eIF4G, is a pivotal factor in the mRNA translation initiation process. eIF4G1, the major paralogue of the three eIF4G family members, is indispensable for development, but its function in learning and memory is unknown. To study the role of eIF4G1 in cognition, we used an eIF4G1 haploinsufficient (eIF4G1-1D) mouse model. The axonal arborization of eIF4G1-1D primary hippocampal neurons was significantly disrupted, and the mice displayed impairment in hippocampus-dependent learning and memory. Translatome analysis showed that the translation of mRNAs encoding proteins of the mitochondrial oxidative phosphorylation (OXPHOS) system was decreased in the eIF4G1-1D brain, and OXPHOS was decreased in eIF4G1-silenced cells. Thus, eIF4G1-mediated mRNA translation is crucial for optimal cognitive function, which is dependent on OXPHOS and neuronal morphogenesis.


Overexpression of Dicer in precursor lesions of lung adenocarcinoma.
Differential microRNA (miR) expression is described in non-small cell lung carcinoma. miR biogenesis requires a set of proteins collectively referred to as the miR machinery. In the proposed multistep carcinogenesis model, peripheral adenocarcinoma of the lung develops from noninvasive precursor lesions known as atypical adenomatous hyperplasia (AAH) and bronchioloalveolar carcinoma (BAC). The gene array analysis of BAC and adenocarcinoma showed a transient up-regulation of Dicer (a key effector protein for small interfering RNA and miR function) and PACT along with down-regulation of most genes encoding miR machinery proteins. Immunohistochemically, Dicer was up-regulated in AAH and BAC and down-regulated in areas of invasion and in advanced adenocarcinoma. A fraction of adenocarcinomas lose Dicer as a result of deletions at the Dicer locus. Expanded immunohistochemical and Western blot analysis showed higher Dicer level in squamous cell carcinoma (SCC) of the lung when compared with adenocarcinoma. Other proteins of the RNA-induced silencing complex (RISC; SND1, PACT, and FXR1) were also present at higher levels in a SCC cell line when compared with an adenocarcinoma cell line. In conclusion, the stoichiometry of miR machinery and RISC depends on histologic subtype of lung carcinoma, varies along the AAH-BAC-adenocarcinoma sequence, and might explain the observed abnormal miR profile in lung cancer. The status of the endogenous miR machinery in various histologic subtypes and stages of lung cancer may help to predict the toxicity of and susceptibility to future RNA interference-based therapy.


Prediction of ocular irritancy of 26 chemicals and 26 cosmetic products with isolated rabbit eye (IRE) test.
This study aims to establish and evaluate the methodology of isolated rabbit eye (IRE) test. IRE test was performed according to modifications of the in vitro toxicology (INVITTOX) Protocol No.85: Rabbit enucleated eye test by European Centre for the Validation of Alternative Methods (ECVAM), and then 26 chemicals and 26 cosmetic products were tested in both in vitro IRE and in vivo Draize tests. A statistical analysis was conducted to determine the relevance of the IRE test to the data generated in the Draize test. IRE test was established successfully in our laboratory. It was shown that ranking correlation and class concordance were fairly well between the IRE test and the Draize test for 26 reference chemicals (Fisher's Exact Test χ(2)=51.314, P<0.001; McNemar P=0.261; Gamma=0.960, P<0.001; Kappa=0.843, P<0.001) and 26 cosmetic products (Fisher's Exact Test χ(2)=15.522, P<0.001; McNemar P=0.311; Gamma=0.967, P<0.001; Kappa=0.611, P<0.001). IRE test was established successfully for in vitro testing of eye irritation as an alternative to Draize test.


Molecular evidence for the first records of facultative parthenogenesis in elapid snakes.
Parthenogenesis is a form of asexual reproduction by which embryos develop from unfertilized eggs. Parthenogenesis occurs in reptiles; however, it is not yet known to occur in the widespread elapid snakes (Elapidae), which include well-known taxa such as cobras, mambas, taipans and sea snakes. Here, we describe the production of viable parthenogens in two species of Australo-Papuan elapids with divergent reproductive modes: the oviparous coastal/Papuan taipan (Oxyuranus scutellatus) and the viviparous southern death adder (Acanthophis antarcticus). Analyses of nuclear SNP data excluded paternity for putative fathers and convincingly demonstrated asexual reproduction, thus representing the first evidence of facultative parthenogenesis in Elapidae. Our finding has broad implications for understanding the evolution of reproductive diversity in snakes, as well as managing the conservation of genetic diversity in wild and captive populations.


Cytoplasmic streaming affects gravity-induced amyloplast sedimentation in maize coleoptiles.
Living maize (Zea mays L.) coleoptile cells were observed using a horizontal microscope to determine the interaction between cytoplasmic streaming and gravity-induced amyloplast sedimentation. Sedimentation is heavily influenced by streaming which may (1) hasten or slow the velocity of amyloplast movement and (2) displace the plastid laterally or even upwards before or after sedimentation. Amyloplasts may move through transvacuolar strands or through the peripheral cytoplasm which may be divided into fine cytoplasmic strands of much smaller diameter than the plastids. The results indicate that streaming may contribute to the dynamics of graviperception by influencing amyloplast movement.


Reovirus protein sigmaNS binds in multiple copies to single-stranded RNA and shares properties with single-stranded DNA binding proteins.
Reovirus nonstructural protein sigmaNS interacts with reovirus plus-strand RNAs in infected cells, but little is known about the nature of those interactions or their roles in viral replication. In this study, a recombinant form of sigmaNS was analyzed for in vitro binding to nucleic acids using gel mobility shift assays. Multiple units of sigmaNS bound to single-stranded RNA molecules with positive cooperativity and with each unit covering about 25 nucleotides at saturation. The sigmaNS protein did not bind preferentially to reovirus RNA over nonreovirus RNA in competition experiments but did bind preferentially to single-stranded over double-stranded nucleic acids and with a slight preference for RNA over DNA. In addition, sigmaNS bound to single-stranded RNA to which a 19-base DNA oligonucleotide was hybridized at either end or near the middle. When present in saturative amounts, sigmaNS displaced this oligonucleotide from the partial duplex. The strand displacement activity did not require ATP hydrolysis and was inhibited by MgCl(2), distinguishing it from a classical ATP-dependent helicase. These properties of sigmaNS are similar to those of single-stranded DNA binding proteins that are known to participate in genomic DNA replication, suggesting a related role for sigmaNS in replication of the reovirus RNA genome.


Persistence and desistance of oppositional defiant disorder in a community sample of children with ADHD.
To examine the developmental progression of comorbid oppositional defiant disorder (ODD) in a community sample of children with attention-deficit hyperactivity disorder (ADHD) with particular emphasis on persistence and desistance of ODD and the emergence of new cases of conduct disorder (CD). A sample of disruptive children was identified from a multiple-gate epidemiological screen and stratified into diagnostic subgroups on the basis of a structured interview. A comparison sample of nondisruptive children was also identified. Group comparisons were performed on demographic, descriptive, family history, and clinical characteristics. Changes in rates of ODD symptoms and diagnostic subgroup membership were assessed after a 4-year longitudinal interval. Predictors of diagnostic group persistence were tested. Few differences distinguished diagnostic subgroups at baseline. Of the 43 children with baseline diagnoses of ADHD + ODD, only 1 (2.3%) was found to have developed CD at follow-up. Over time there was a 57% rate of ODD persistence and a 43% rate of ODD desistance. Negative parenting practices and mothers' psychiatric disorders predicted persistence of ODD. There was little evidence to show that ODD acted as a precursor to CD. However, when CD was diagnosed at baseline it was always associated with or preceded by ODD (i.e., prodrome). For a subgroup of children with ADHD, comorbid ODD symptoms are relatively unstable and may represent transient developmental perturbations that have little prognostic significance. For a larger subgroup of children with ADHD, ODD symptoms persist into the adolescent years and are associated with adverse parenting practices.


Smoke exposure among women in Haiti: the case for improved stoves.
Indoor smoke exposure is responsible for two million deaths per year and has been studied globally, but the impacts of exposure have not yet been evaluated in Haiti, the Western hemisphere's poorest nation. This study measures the disproportionate impact of indoor smoke exposure on the women and children of Haiti. We studied 2296 clinic patients in four Haitian villages to determine the extent of carbon monoxide (CO) exposure, using carboxyhemoglobin saturation in the blood as a proxy for overall smoke exposure. We predicted CO levels to be higher in women, who traditionally perform the majority of cooking duties, and in children who accompany their mothers. CO levels averaged 4.9% in women and 3.4% in men. Women of child-bearing age carried a minimum relative risk (RR) for CO exposure of 1.22, relative to all males and younger females. Older females carried no significant difference in risk. Children averaged the lowest CO exposure among all cohorts. These findings demonstrate the burden of indoor smoke exposure that falls disproportionately on women in these regions of Haiti. Global efforts to mitigate indoor exposure have demonstrated the health, economic, environmental and social improvements that are possible by tackling this problem.


Nuclear trapping shapes the terminal gradient in the Drosophila embryo.
Patterning of the terminal regions of the Drosophila embryo relies on the gradient of phosphorylated ERK/MAPK (dpERK), which is controlled by the localized activation of the Torso receptor tyrosine kinase [1-4]. This model is supported by a large amount of data, but the gradient itself has never been quantified. We present the first measurements of the dpERK gradient and establish a new intracellular layer of its regulation. Based on the quantitative analysis of the spatial pattern of dpERK in mutants with different levels of Torso as well as the dynamics of the wild-type dpERK pattern, we propose that the terminal-patterning gradient is controlled by a cascade of diffusion-trapping modules. A ligand-trapping mechanism establishes a sharply localized pattern of the Torso receptor occupancy on the surface of the embryo. Inside the syncytial embryo, nuclei play the role of traps that localize diffusible dpERK. We argue that the length scale of the terminal-patterning gradient is determined mainly by the intracellular module.


Multimodal Nonopioid Pain Protocol Provides Equivalent Pain Versus Opioid Control Following Meniscus Surgery: A Prospective Randomized Controlled Trial.
To assess the effectiveness of a nonopioid pain regimen in controlling postoperative pain as compared with a traditional opioid pain control following primary meniscectomy or meniscal repair. Ninety-nine patients undergoing primary meniscectomy or meniscal repair were assessed for participation. A prospective randomized control trial was performed in accordance with the Consolidated Standards of Reporting Trials 2010 statement. The 2 arms of the study included a multimodal nonopioid analgesic protocol and a standard opioid regimen with a primary outcome of postoperative pain level (visual analog scale) for the first 10 days postoperatively. Secondary outcomes included patient-reported outcomes, complications, and patient satisfaction. Randomization was achieved using a random-number generator. Patients were not blinded. Data collection was done by a blinded observer. Eleven patients did not meet the inclusion criteria, and 27 declined participation. A total of 61 patients were analyzed with 30 randomized to the opioid regimen and 31 randomized to the nonopioid regimen. Patients receiving the nonopioid regimen demonstrated noninferior visual analog scale scores compared with patients who received opioid pain medication (P > .05). No significant differences were found in preoperative (opioid: 58.9 ± 7.0; nonopioid: 58.2 ± 5.5, P = .724) or postoperative (opioid: 59.8 ± 6.5; nonopioid: 54.9 ± 7.1, P = .064) Patient-Reported Outcomes Measurement and Information System Pain Interference Short Form scores. No difference was found in recorded side effects between both groups at any given time point: constipation, nausea, diarrhea, upset stomach, and drowsiness (P > .05). This study found that a multimodal nonopioid pain protocol provided equivalent pain control and patient outcomes following primary meniscus surgery while having an equivalent side effect profile. All patients reported satisfaction with their pain management without requiring emergency opioid analgesia. Level I, prospective randomized controlled trial.


The CD40/CD154 receptor/ligand dyad.
Until recently, the expression and primary function of the cell surface receptor CD40 and its ligand CD154 were considered restricted to B and T lymphocytes, and their interactions required for the thymus-dependent humoral response. However, current work from several groups challenges this view of the CD40/CD154 dyad as a mere mediator of lymphocyte communication. A variety of non-lymphocytic cell types express both receptor and ligand, including hematopoetic and non-hematopoetic cells, such as monocytes, basophils, eosinophils, dendritic cells, fibroblasts, smooth muscle, and endothelial cells. Accordingly, ligation of CD40 mediates a broad variety of immune and inflammatory responses, such as the expression of adhesion molecules, cytokines, matrix-degrading enzymes, prothrombotic activities, and apoptotic mediators. Consequently, CD40 signaling has been associated with pathogenic processes of chronic inflammatory diseases, such as autoimmune diseases, neurodegenerative disorders, graft-versus-host disease, cancer, and atherosclerosis. This review focuses on the synthesis and structure of CD40 and outlines CD154/CD40 signaling pathways, and emphasizes the previously unexpected importance of the CD40/CD154 receptor/ligand dyad in a spectrum of immunoregulatory processes and prevalent human diseases.


Multi-Camera Trajectory Forecasting With Trajectory Tensors.
We introduce the problem of multi-camera trajectory forecasting (MCTF), which involves predicting the trajectory of a moving object across a network of cameras. While multi-camera setups are widespread for applications such as surveillance and traffic monitoring, existing trajectory forecasting methods typically focus on single-camera trajectory forecasting (SCTF), limiting their use for such applications. Furthermore, using a single camera limits the field-of-view available, making long-term trajectory forecasting impossible. We address these shortcomings of SCTF by developing an MCTF framework that simultaneously uses all estimated relative object locations from several viewpoints and predicts the object's future location in all possible viewpoints. Our framework follows a Which-When-Where approach that predicts in which camera(s) the objects appear and when and where within the camera views they appear. To this end, we propose the concept of trajectory tensors: a new technique to encode trajectories across multiple camera views and the associated uncertainties. We develop several encoder-decoder MCTF models for trajectory tensors and present extensive experiments on our own database (comprising 600 hours of video data from 15 camera views) created particularly for the MCTF task. Results show that our trajectory tensor models outperform coordinate trajectory-based MCTF models and existing SCTF methods adapted for MCTF. Code is available from: https://github.com/olly-styles/Trajectory-Tensors.


Impact of carbon monoxide partial pressures on methanogenesis and medium chain fatty acids production during ethanol fermentation.
Medium-chain fatty acids (MCFA) are important biofuel precursors. Carbon monoxide (CO) is a sustainable electron and carbon donor for fatty acid elongation, since it is metabolized to MCFA precursors, it is toxic to most methanogens, and it is a waste product generated in the gasification of waste biomass. The main objective of this work was to determine if the inhibition of methanogenesis through the continuous addition of CO would lead to increased acetate or MCFA production during fermentation of ethanol. The effects of CO partial pressures (PCO ; 0.08-0.3 atm) on methanogenesis, fatty acids production, and the associated microbial communities were studied in batch cultures fed with CO and ethanol. Methanogenesis was partially inhibited at PCO ≥ 0.11 atm. This inhibition led to increased acetate production during the first phase of fermentation (0-19 days). However, a second addition of ethanol (day 19) triggered MCFA production only at PCO ≥ 0.11 atm, which probably occurred through the elongation of acetate with CO-derived ethanol and H2 :CO2 . Accordingly, during the second phase of fermentation (days 20-36), the distribution of electrons to acetate decreased at higher PCO , while electrons channeled to MCFA increased. Most probably, Acetobacterium, Clostridium, Pleomorphomonas, Oscillospira, and Blautia metabolized CO to H2 :CO2 , ethanol and/or fatty acids, while Peptostreptococcaceae, Lachnospiraceae, and other Clostridiales utilized these metabolites, along with the provided ethanol, for MCFA production. These results are important for biotechnological systems where fatty acids production are preferred over methanogenesis, such as in chain elongation systems and microbial fuel cells.


Evaluating the usage of droperidol in acutely agitated persons with brain injury.
The objective of this study was to compare the effectiveness and safety of intramuscular droperidol to other intramuscularly administered agents used in the management of acutely agitated patients. Twenty-seven inpatients with a history of brain injury were prospectively monitored over a period of 2 months. Data collected for each episode of agitation include: dose, number of doses, time to achieve an adequate response or calming effect, post-episodic functioning, treatment-emergent side effects, and other patient demographics. A retrospective medical records review was also performed on the same cohort, to compare clinical outcomes associated with other intramuscular agents previously used for acute agitation. Time to achieve calming was significantly shorter with intramuscular droperidol (mean = 27.0 minutes) compared to intramuscular haloperidol, lorazepam, or diphenhydramine (group mean = 36.2 minutes, p = 0.02). Of the three comparative agents, the time to achieve calming was the fastest with lorazepam (mean = 35.0 minutes), and slower with diphenhydramine (mean = 42.6 minutes) and haloperidol (mean = 43.0 minutes). Single doses of droperidol controlled agitation more frequently than did single doses of comparative agents, and there was less post-episodic sedation with droperidol following release from seclusion or restraints. Both groups were similar in regard to the incidence of treatment-emergent events. This data represents the first published experience supporting the effectiveness of droperidol in reducing acute agitation in persons with brain injury. Follow-up studies with prospective, double-blind, parallel treatment groups should be performed to validate these preliminary findings.


M2 muscarinic receptor activation regulates Schwann cell differentiation and myelin organization.
Glial cells express acetylcholine receptors. In particular, rat Schwann cells express different muscarinic receptor subtypes, the most abundant of which is the M2 subtype. M2 receptor activation causes a reversible arrest of the cell cycle. This negative effect on Schwann cell proliferation suggests that these cells may possibly progress into a differentiating program. In this study we analyzed the in vitro modulation, by the M2 agonist arecaidine, of transcription factors and specific signaling pathways involved in Schwann cell differentiation. The arecaidine-induced M2 receptor activation significantly upregulates transcription factors involved in the promyelinating phase (e.g., Sox10 and Krox20) and downregulates proteins involved in the maintenance of the undifferentiated state (e.g., c-jun, Notch-1, and Jagged-1). Furthermore, arecaidine stimulation significantly increases the expression of myelin proteins, which is accompanied by evident changes in cell morphology, as indicated by electron microscopy analysis, and by substantial cellular re-distribution of actin and cell adhesion molecules. Moreover, ultrastructural and morphometric analyses on sciatic nerves of M2/M4 knockout mice show numerous degenerating axons and clear alterations in myelin organization compared with wild-type mice. Therefore, our data demonstrate that acetylcholine mediates axon-glia cross talk, favoring Schwann cell progression into a differentiated myelinating phenotype and contributing to compact myelin organization.


The use of echocardiography in Wolff-Parkinson-White syndrome.
Endocardial mapping and radiofrequency catheter ablation are well established modalities for the diagnosis and treatment of patients with Wolff-Parkinson-White (WPW) syndrome associated with tachyarrhythmias. However, the electrophysiologic techniques are invasive, require radiation exposure, and lack spatial resolution of cardiac structures. A variety of echocardiographic techniques have been investigated as a non-invasive alternative for accessory pathway localization. Conventional M-mode echocardiography can detect the fine premature wall motion abnormalities associated with WPW syndrome. However, it is unable to identify the exact site of accessory pathway with sufficient accuracy. 2D, 2D-guided M-mode, and 2D phase analysis techniques are limited by image quality and endocardial border definition. Various modalities of tissue Doppler echocardiography significantly increase the accuracy of left-sided accessory pathway localization to 80-90% even in patients with poor acoustic window. However, right-sided pathways remain a diagnostic challenge. Strain echocardiography by speckle tracking has recently been evaluated and appears promising. Different cardiac abnormalities have been detected by echocardiography in WPW patients. Patients with WPW syndrome and tachyarrhythmias have impaired systolic and diastolic function which improves after radiofrequency ablation. Echocardiography is useful in identifying patient with accessory pathway-associated left ventricular dyssynchrony and dysfunction who may benefit from ablation therapy. Transesophageal and intracardiac echocardiography have been used to guide ablation procedure. Ablation-related complications detected by routine echocardiography are infrequent, rarely clinically relevant, and of limited value.


Inadequate fruit and vegetable intake in people with psychosis.
The objective of this study was to identify factors associated with poor dietary intake (less than four servings of fruit and vegetables daily) in a large nationally representative sample of adults with psychotic disorders. The sample comprised 1286 adults aged 18-64 years who took part in the second Australian national survey of psychosis. Dietary information was obtained using a standardised questionnaire; all participants provided fasting blood samples. Variables that may be related to diet and nutritional intake were investigated; these included demographics, physical health outcomes, physical activity, substance use, symptom severity and financial difficulty. Dietary status was explored by sex, age and body mass index using univariate analyses, while a multivariate analysis was performed to identify predictors of low nutritional intake. Approximately 74% of participants ate less than four servings of fruit and vegetables daily. This was associated with a lower body mass index (p<0.05), lower levels of physical activity (p<0.05), sedentary behaviour (p<0.05), substance use (p<0.001), more negative symptoms (p<0.05), eating less frequently (p<0.001), consuming whole fat milk compared to low fat milk (p<0.05), adding salt to food (p<0.05) and financial difficulty (p<0.05). Male sex and younger age (18-34 years) were also associated with lower fruit and vegetable intake (p<0.001). A multivariate regression analysis showed that current smoking (p<0.001) and alcohol (p<0.01) and cannabis abuse (p<0.05) were risk factors for lower fruit and vegetable intake. The findings suggest that poor diet in people with psychosis, as reflected by less than four servings of fruit and vegetables daily, is accompanied by other unhealthy behaviours, which has important implications for the development of effective interventions. Importantly, current smoking is a significant predictor of dietary inadequacy.


[In vitro cultivation of human chondrocytes using autologous human serum supplemented culture medium: minimizing possible risk of infection with pathogens of prion diseases].
The in vitro engineering of autologous transplant might play an important role in reconstructive surgery in the near future. The amplification of isolated cells is an important part of the engineering. Because of the use of fetal calf serum (fcs) in the cellculture, there is a potential risk of transmission of prion diseases. The aim of this study was to evaluate a way of amplifying chondrocytes with autologous human serum instead of fcs and to compare the rates of proliferation. For this purpose the isolated chondrocytes were cultured using complete medium, with 10% fcs or 10% autologous human serum being added to the medium. The experiments show that a culture with complete medium and autologous human serum allows a 150 to 300fold increase in the number of cells after 40 days of culture and the proliferation is up to 3fold higher than in cultures using fcs. Chondrocytes can be stimulated by autologous human serum to proliferate. It is possible to avoid fcs in the culture of chondrocytes and to minimize the risk of an infection with prions.


Exploration of Graphene Defect Reactivity toward a Hydrogen Radical Utilizing a Preactivated Circumcoronene Model.
A preexisting chemisorbed defect is well-known to increase the reactivity of graphene which is normally chemically inert. Specifically, the presence of chemisorbed hydrogen atoms forming an sp3-hybridized C-H bond is known to increase the reactivity of neighboring carbon atoms toward additional hydrogenation with wide-ranging applications from materials science to astrochemistry. In this work, static DFT and DFT-based direct dynamics simulations are used to characterize the reactivity of a graphene sheet around an existing C-H bond defect. The spin density landscape shows how to guide subsequent H atom additions, always bonding most strongly to the carbon atom with greatest spin density. Molecular dynamics of an impinging H atom under thermal conditions with defect graphene was used to determine the statistics of probable reactions. The most frequent outcome is inelastic scattering (48%) and then Eley-Rideal (ER) abstraction of the chemisorbed H atom as vibrationally hot H2 (40%), while the least likely, but probably most interesting, result is formation of a novel C-H bond (12%). The C-H bonds always form in the β sublattice. The carbon atom in the para position shows to be most reactive toward the incoming H atom, followed by the ortho carbon, in agreement with the spin density computed in the static calculations. Globally, the graphene energy surface is repulsive, but the defects create local channels into this energy surface through which reactants can move locally through and react with the activated surface without a barrier.


Genome sequence of a nephritogenic and highly transformable M49 strain of Streptococcus pyogenes.
The 1,815,783-bp genome of a serotype M49 strain of Streptococcus pyogenes (group A streptococcus [GAS]), strain NZ131, has been determined. This GAS strain (FCT type 3; emm pattern E), originally isolated from a case of acute post-streptococcal glomerulonephritis, is unusually competent for electrotransformation and has been used extensively as a model organism for both basic genetic and pathogenesis investigations. As with the previously sequenced S. pyogenes genomes, three unique prophages are a major source of genetic diversity. Two clustered regularly interspaced short palindromic repeat (CRISPR) regions were present in the genome, providing genetic information on previous prophage encounters. A unique cluster of genes was found in the pathogenicity island-like emm region that included a novel Nudix hydrolase, and, further, this cluster appears to be specific for serotype M49 and M82 strains. Nudix hydrolases eliminate potentially hazardous materials or prevent the unbalanced accumulation of normal metabolites; in bacteria, these enzymes may play a role in host cell invasion. Since M49 S. pyogenes strains have been known to be associated with skin infections, the Nudix hydrolase and its associated genes may have a role in facilitating survival in an environment that is more variable and unpredictable than the uniform warmth and moisture of the throat. The genome of NZ131 continues to shed light upon the evolutionary history of this human pathogen. Apparent horizontal transfer of genetic material has led to the existence of highly variable virulence-associated regions that are marked by multiple rearrangements and genetic diversification while other regions, even those associated with virulence, vary little between genomes. The genome regions that encode surface gene products that will interact with host targets or aid in immune avoidance are the ones that display the most sequence diversity. Thus, while natural selection favors stability in much of the genome, it favors diversity in these regions.


Patient Benefits of Radical Prostatectomy in Certified Prostate Cancer Centers: Comparative Results from the Multicenter IMPROVE Study.
We investigated differences in treatment outcomes following radical prostatectomy (RP) between certified centers (CCs) and noncertified centers (nCCs) within the IMPROVE study group. A validated survey assessing various factors, including stress urinary incontinence (SUI) and decision regret (DR), was administered to 950 patients who underwent RP across 19 hospitals (12 CCs and 7 nCCs) at a median follow-up of 15 months after RP (interquartile range: 11-20). The response rate was 74%, with 703 patients participating, including 480 (68%) from CCs. Multivariate binary regression models were used to analyze differences between CCs and nCCs regarding the following binary endpoints: nerve-sparing (NS), positive surgical margins (PSM), SUI (defined as >1 safety pad), complications based on the Clavien-Dindo classification (grade ≥1, grade ≥3) and DR (>15 points indicating critical DR). Considering the multivariate analysis, the rate of NS surgery was lower in CCs than in nCCs (OR = 0.52; p = 0.004). No significant differences were observed in the PSM rate (OR = 1.67; p = 0.051), SUI (OR = 1.03; p = 0.919), and DR (OR = 1.00; p = 0.990). SUI (OR 0.39; p < 0.001) and DR (OR 0.62; p = 0.026) were reported significantly less frequently by patients treated with robotic-assisted RP, which was significantly more often performed in CCs than in nCCs (68.3% vs. 18%; p < 0.001). The total complication rate was 45% lower in CCs (OR = 0.55; p = 0.004), although the number of complications requiring intervention (Clavien-Dindo classification ≥3) did not differ significantly between CCs and nCCs (OR = 2.52; p = 0.051). Within the IMPROVE study group, similarly favorable outcomes after RP were found in both CCs and nCCs, which, however, cannot be transferred to the general treatment landscape of PCA in Germany. Of note, robotic-assisted RP was more often performed in CCs and associated with less SUI and DR, while open prostatectomy was the treatment of choice in low-volume nCCs. Future prospective and region wide studies should also investigate the surgeon caseload and experience as well as a spillover effect of the certification process on nCCs.


Paget's disease of bone in patients younger than 40 years.
Paget's disease of bone, although common in the United States, is relatively rare in patients younger than 40 years. In a large archival series, 10% of patients with Paget's disease of bone were younger than 40 years. Pain followed by pathologic fracture was the most common presenting complaint in this group of patients. There was no gender difference comparing the younger group with the older group of patients. Of the 521 patients in this series, only 10 were African-American; the others were Caucasians. Seven African-American patients were in the group of patients who were younger than 40 years. Appendicular and monostotic bone involvement was more frequent in the younger age group although these differences were not statistically significant. The incidence of malignant transformation in pagetic bone was high (30.3%), and is a reflection of the high volume of uncommon tumor referrals to our consultation service. However, there were no cases of associated malignancies in the group of patients younger than 40 years.


Synovial chondromatosis caused mechanical snapping elbow: a case report.
Synovial chondromatosis is a rare and benign proliferative disorder of the synovial membrane in joints and bursae. Herein, we present the case of a 34-year-old male with synovial chondromatosis that caused limitation in the elbow joint in terms of mechanical function.


The roles of IGF2 and DNMT methylation and elongase6 related fatty acids in metabolic syndrome.
Background: The prevalence of metabolic syndrome (MetS) has increased along with rapid socio-economic development in China in recent decades, aggravating the burden of the health care system. Both plasma levels of fatty acids (FAs) and aberrant DNA methylation profiles are associated with MetS risk. However, studies exploring the role of DNA methylation and FAs simultaneously in MetS etiology are sparse. Objective: We aimed to explore the association between the gene methylation levels of insulin-like growth factor II (IGF2), H19, DNA methyltransferases 1 (DNMT1), DNA methyltransferases 3a (DNMT3a), and DNA methyltransferases 3b (DNMT3b) and MetS risk, and the etiological role of elongation of very-long-chain fatty acid elongase 6 (ELOVL6) related fatty acids. Method: Plasma levels of FAs were measured using a Gas Chromatography-Flame Ionization Detector (GC-FID) after organic extraction, and gene methylation was quantified using a real-time Quantitative Polymerase Chain Reaction (Q-PCR) detecting system after bisulfite treatment. The C18/C16 ratio was used as the indicator of ELOVL6 activity. Odds Ratio (OR) and 95% Confidence Interval (CI) were estimated with logistic regression. Results: Methylation levels in IGF2 and DNMT3a were not significantly associated with MetS risk. However, when stratified by C18/C16 ratio (high vs. low), positive associations were observed between the risk of MetS and methylation levels (>median) of IGF2a3 (OR = 3.1, 95% CI = 1.3-7.5) and DNMT3a (OR = 2.5, 95% CI = 1.1-5.8) genes, in individuals with lower C18/C16 ratios, while no significant associations were observed in subjects with high C18/C16 ratios. Conclusion: Methylation levels in IGF2 and DNMT3a genes may affect the risk of MetS in an ELOVL6 activity-dependent way among Chinese adults. Further studies in other populations are needed to validate this finding.


Hospital employees' theoretical knowledge on what to do in an in-hospital cardiac arrest.
Guidelines recommend that all health care professionals should be able to perform cardiopulmonary resuscitation (CPR), including the use of an automated external defibrillator. Theoretical knowledge of CPR is then necessary.The aim of this study was to investigate how much theoretical knowledge in CPR would increase among all categories of health care professionals lacking training in CPR, in an intervention hospital, after a systematic standardised training. Their results were compared with the staff at a control hospital with an ongoing annual CPR training programme. Health care professionals at two hospitals, with a total of 3144 employees, answered a multiple-choice questionnaire before and after training in CPR. Bootstrapped chi-square tests and Fisher's exact test were used for the statistical analyses. In the intervention hospital, physicians had the highest knowledge pre-test, but other health care professionals including nurses and assistant nurses reached a relatively high level post-test. Improvement was inversely related to the level of previous knowledge and was thus most marked among other health care professionals and least marked among physicians.The staff at the control hospital had a significantly higher level of knowledge pre-test than the intervention hospital, whereas the opposite was found post-test. Overall theoretical knowledge increased after systematic standardised training in CPR. The increase was more pronounced for those without previous training and for those staff categories with the least medical education.


Scanning capacitance microscopy registration of buried atomic-precision donor devices.
We show that a scanning capacitance microscope (SCM) can image buried delta-doped donor nanostructures fabricated in Si via a recently developed atomic-precision scanning tunneling microscopy (STM) lithography technique. A critical challenge in completing atomic-precision nanoelectronic devices is to accurately align mesoscopic metal contacts to the STM defined nanostructures. Utilizing the SCMs ability to image buried dopant nanostructures, we have developed a technique by which we are able to position metal electrodes on the surface to form contacts to underlying STM fabricated donor nanostructures with a measured accuracy of 300 nm. Low temperature (T = 4 K) transport measurements confirm successful placement of the contacts to the donor nanostructures.


Drosophila MCRS2 associates with RNA polymerase II complexes to regulate transcription.
Drosophila MCRS2 (dMCRS2; MCRS2/MSP58 and its splice variant MCRS1/p78 in humans) belongs to a family of forkhead-associated (FHA) domain proteins. Whereas human MCRS2 proteins have been associated with a variety of cellular processes, including RNA polymerase I transcription and cell cycle progression, dMCRS2 has been largely uncharacterized. Recent data show that MCRS2 is purified as part of a complex containing the histone acetyltransferase MOF (males absent on first) in both humans and flies. MOF mediates H4K16 acetylation and regulates the expression of a large number of genes, suggesting that MCRS2 could also have a function in transcription regulation. Here, we show that dMCRS2 copurifies with RNA polymerase II (RNAP II) complexes and localizes to the 5' ends of genes. Moreover, dMCRS2 is required for optimal recruitment of RNAP II to the promoter regions of cyclin genes. In agreement with this, dMCRS2 is required for normal levels of cyclin gene expression. We propose a model whereby dMCRS2 promotes gene transcription by facilitating the recruitment of RNAP II preinitiation complexes (PICs) to the promoter regions of target genes.


Delivering gene therapy for mucopolysaccharide diseases.
Mucopolysaccharide diseases are a group of paediatric inherited lysosomal storage diseases that are caused by enzyme deficiencies, leading to a build-up of glycosaminoglycans (GAGs) throughout the body. Patients have severely shortened lifespans with a wide range of symptoms including inflammation, bone and joint, cardiac, respiratory and neurological disease. Current treatment approaches for MPS disorders revolve around two main strategies. Enzyme replacement therapy (ERT) is efficacious in treating somatic symptoms but its effect is limited for neurological functions. Haematopoietic stem cell transplant (HSCT) has the potential to cross the BBB through monocyte trafficking, however delivered enzyme doses limit its use almost exclusively to MPSI Hurler. Gene therapy is an emerging therapeutic strategy for the treatment of MPS disease. In this review, we will discuss the various vectors that are being utilised for gene therapy in MPS as well as some of the most recent gene-editing approaches undergoing pre-clinical and clinical development.


Bentall operation in 375 patients: long-term results and predictors of death.
The Bentall operation is a 40-year-old standardized procedure for treating aortic valve diseases and aneurysms involving the aortic root. The study aim was to analyze the results and predictors of long-term outcome after the Bentall procedure for aortic root diseases. Between January 1990 and December 2007, a total of 375 patients (296 males, 79 females) underwent the Bentall operation at the authors' institution. Bicuspid aortic valve (BAV) was present in 91 patients, and Marfan syndrome in 13. Thirty-six patients were treated as emergencies, and 30 for acute dissection. A concomitant surgical procedure was performed in 78 patients. The operative procedure included both classic Bentall and button techniques. Follow up data were obtained from hospital and office records and from telephone contacts. Kaplan-Meier survival analysis and Cox regression analysis were performed to investigate the predictors of long-term outcome. The overall in-hospital mortality was 4.5%, and after elective operations was 2.3%. A 20-year long-term follow up included 32 late deaths, of which 14 were cardiac-related. Freedom from late all-cause mortality at 5, 10, and 15 years was 97.1%, 81.9%, and 53.9%, respectively. At univariate analysis, long-term mortality was associated with age, diabetes, BAV, NYHA class III/IV, emergency treatment, cardiopulmonary bypass time, and coronary artery bypass grafting. Independent predictors of long-term mortality were age (OR 1.16; CI: 1.08-1.23), emergency surgery (OR 28; CI: 4-192) and BAV (OR 3; CI: 1.3-6.9). The Bentall procedure is a safe and durable operation, with a very good early and long-term results and a low rate of reoperation. In the present series, age, BAV and emergency surgery were important independent predictors of mortality.


Event-Based Surveillance of Poisonings and Potentially Hazardous Exposures over 12 Months of the COVID-19 Pandemic.
The COVID-19 pandemic has seen people and governments utilise an array of chemical and pharmaceutical substances in an attempt to prevent and treat COVID-19 infections. The Centre for Radiation, Chemicals and Environmental Hazards (CRCE) at Public Health England (PHE) routinely undertakes Event-Based Surveillance (EBS) to monitor public health threats and incidents related to chemicals and poisons. From April 2020, EBS functions were expanded to screen international media for potentially hazardous exposures associated with the COVID-19 pandemic. Media sources reported that poisons centres were experiencing increased enquiries associated with the use and misuse of household cleaners and alcohol-based hand sanitiser (HS). There were also media reports of people self-medicating with over-the-counter supplements and traditional or herbal remedies. Public figures who directly or indirectly facilitated misinformation were sometimes reported to be associated with changes in poisoning trends. Border closures were also believed to have been associated with increasingly toxic illicit drug supplies in Canada, and record numbers of opioid-related deaths were reported. In other countries, where the sale of alcohol was banned or limited, home-brewing and methanol-based supplies resulted in a number of fatalities. At least two chemical incidents also occurred at industrial sites in India, after sites were left unattended or were closed and reopened due to lockdown measures. Reports of poisoning identified in the international media were provided to the UK National Poisons Information Service (NPIS) and contributed to the UK COVID-19 public health response.


A single beam near-field laser trap for optical stretching, folding and rotation of erythrocytes.
To understand the fundamental mechanical and viscoelastic properties of RBCs, one needs laser tweezers in which cells can not only be trapped, but also be stretched, folded, and rotated. Stretching, folding and rotating an RBC is particularly important in order to reveal the shear elasticity of the RBC membrane. Here we show a single beam near-field laser trapping technique under focused evanescent wave illumination for optical stretching, folding and rotation of a single RBC. This multifunctional manipulation method will provide a new platform for measuring cell properties such as the membrane elasticity, viscoelasticity and deformability.


Evolution of preferences for COVID-19 vaccine throughout the pandemic - The choice experiment approach.
In this study, we employ a choice experiment to study individual preferences for COVID-19 vaccines in the US. A unique characteristic of the microdata (N = 5671) is that the survey was conducted in five distinct waves from October 2020 to October 2021. Because of this dynamic feature, it is possible to control for evolving pandemic conditions such as the number of COVID-19 active cases, vaccination uptake, and the frequency of Google searches related to the vaccines. Furthermore, we employ a hybrid choice model to incorporate respondents' attitudes related to their perceived vulnerability to diseases, as well as their perceived health status. The hybrid choice model was extended to incorporate latent classes as well as random effects. We find that the rate of vaccinated individuals in the population actually increases the probability of vaccine hesitancy, and therefore may discourage people to get vaccinated. This may be evidence of free-riding behavior. On the other hand, the number of COVID-19 cases has a positive effect on the probability of getting vaccinated, suggesting that individuals react to the pandemic conditions by taking some protective measures. Google trend data do not seem to have a straightforward effect on the vaccination demand, but it increases consumers' willingness to pay for several vaccine characteristics. With respect to the analyzed attitudes, we find that perceived uninfectability is a significant driver of vaccine hesitancy, probably related to the frequent "natural immunity" argument. In turn, germ aversion has a positive effect on the probability of getting vaccinated as well as on the marginal willingness to pay. Finally, health status has a limited effect on whether the individual will decide to vaccinate or not.


Abnormal ventromedial prefrontal cortex function in children with psychopathic traits during reversal learning.
Children and adults with psychopathic traits and conduct or oppositional defiant disorder demonstrate poor decision making and are impaired in reversal learning. However, the neural basis of this impairment has not previously been investigated. Furthermore, despite high comorbidity of psychopathic traits and attention-deficit/hyperactivity disorder, to our knowledge, no research has attempted to distinguish neural correlates of childhood psychopathic traits and attention-deficit/hyperactivity disorder. To determine the neural regions that underlie the reversal learning impairments in children with psychopathic traits plus conduct or oppositional defiant disorder. Case-control study. Government clinical research institute. Forty-two adolescents aged 10 to 17 years: 14 with psychopathic traits and oppositional defiant disorder or conduct disorder, 14 with attention-deficit/hyperactivity disorder only, and 14 healthy controls. Blood oxygenation level-dependent signal as measured via functional magnetic resonance imaging during a probabilistic reversal task. Children with psychopathic traits showed abnormal responses within the ventromedial prefrontal cortex (Brodmann area 10) during punished reversal errors compared with children with attention-deficit/hyperactivity disorder and healthy children (P < .05 corrected for multiple comparisons). To our knowledge, this study provides the first evidence of abnormal ventromedial prefrontal cortex responsiveness in children with psychopathic traits and demonstrates this dysfunction was not attributable to comorbid attention-deficit/hyperactivity disorder. These findings suggest that reversal learning impairments in patients with developmental psychopathic traits relate to abnormal processing of reinforcement information.


Expression of hepatitis B antigens with a simian virus 40 vector.
Recombinant DNA molecules consisting of the simian virus 40 (SV40) early region and different subgenomic hepatitis B virus DNA fragments were constructed in vitro and packaged in vivo into SV40 capsids by using a complementing SV40 helper virus. Upon infection with these virus stocks the three known hepatitis B-specific antigens were expressed under SV40 control. The surface antigen was released into the medium, and the core antigen and its derivative hepatitis B e antigen were only detected intracellularly. Size analysis of the core gene product(s) by immunoblotting revealed the presence of a single protein species identical with the 21-kilodalton core antigen isolated from human liver. The hepatitis B core antigen expressing construct did not contain a putative precore sequence, indicating that such a sequence is not needed for hepatitis B core antigen synthesis in animal cells. S1 analysis demonstrated the use of SV40 signals for initiation and polyadenylation of the core gene transcripts. In addition, a processing-polyadenylation signal was identified within the core gene.


Patterns of Emergency Care for Possible Acute Coronary Syndrome Among Patients with Chest Pain or Shortness of Breath at a Tanzanian Referral Hospital.
Acute coronary syndrome (ACS) is thought to be a rare diagnosis in sub-Saharan Africa, but little is known about diagnostic practices for patients with possible ACS symptoms in the region. To describe current care practices for patients with ACS symptoms in Tanzania to identify factors that may contribute to ACS under-detection. Emergency department patients with chest pain or shortness of breath at a Tanzanian referral hospital were prospectively observed. Medical histories were obtained, and diagnostic workups, treatments, and diagnoses were recorded. Five-year risk of cardiovascular events was calculated via the Harvard National Health and Nutrition Examination Survey risk score. Telephone follow-ups were conducted 30 days after enrollment. Of 339 enrolled patients, the median (IQR) age was 60 (46, 72) years, 252 (74.3%) had hypertension, and 222 (65.5%) had >10% five-year risk of cardiovascular event. The median duration of symptoms prior to presentation was 7 days, and 314 (92.6%) reported symptoms worsened by exertion. Of participants, 170 (50.1%) received an electrocardiogram, and 9 (2.7%) underwent cardiac biomarker testing. There was no univariate association between five-year cardiovascular risk and decision to obtain an electrocardiogram (p = 0.595). The most common physician-documented diagnoses were symptomatic hypertension (104 patients, 30.7%) and heart failure (99 patients, 29.2%). Six patients (1.8%) were diagnosed with ACS, and 3 (0.9%) received aspirin. Among 284 (83.8%) patients completing 30-day follow-up, 20 (7.0%) had died. Many patients with ACS risk factors present to the emergency department of a Tanzanian referral hospital with possible ACS symptoms, but marked delays in care-seeking are common. Complete diagnostic workups for ACS are uncommon, ACS is rarely diagnosed or treated with evidence-based therapies, and mortality in patients with these symptoms is high. Physician practices may be contributing to ACS under-detection in Tanzania, and interventions are needed to improve ACS care.


Bioconversion of D-galacturonate to keto-deoxy-L-galactonate (3-deoxy-L-threo-hex-2-ulosonate) using filamentous fungi.
The D-galacturonic acid derived from plant pectin can be converted into a variety of other chemicals which have potential use as chelators, clarifiers, preservatives and plastic precursors. Among these is the deoxy-keto acid derived from L-galactonic acid, keto-deoxy-L-galactonic acid or 3-deoxy-L-threo-hex-2-ulosonic acid. The keto-deoxy sugars have been found to be useful precursors for producing further derivatives. Keto-deoxy-L-galactonate is a natural intermediate in the fungal D-galacturonate metabolic pathway, and thus keto-deoxy-L-galactonate can be produced in a simple biological conversion. Keto-deoxy-L-galactonate (3-deoxy-L-threo-hex-2-ulosonate) accumulated in the culture supernatant when Trichoderma reesei Δlga1 and Aspergillus niger ΔgaaC were grown in the presence of D-galacturonate. Keto-deoxy-L-galactonate accumulated even if no metabolisable carbon source was present in the culture supernatant, but was enhanced when D-xylose was provided as a carbon and energy source. Up to 10.5 g keto-deoxy-L-galactonate l(-1) was produced from 20 g D-galacturonate l(-1) and A. niger ΔgaaC produced 15.0 g keto-deoxy-L-galactonate l(-1) from 20 g polygalacturonate l(-1), at yields of 0.4 to 1.0 g keto-deoxy-L-galactonate [g D-galacturonate consumed](-1). Keto-deoxy-L-galactonate accumulated to concentrations of 12 to 16 g l(-1) intracellularly in both producing organisms. This intracellular concentration was sustained throughout production in A. niger ΔgaaC, but decreased in T. reesei. Bioconversion of D-galacturonate to keto-deoxy-L-galactonate was achieved with both A. niger ΔgaaC and T. reesei Δlga1, although production (titre, volumetric and specific rates) was better with A. niger than T. reesei. A. niger was also able to produce keto-deoxy-L-galactonate directly from pectin or polygalacturonate demonstrating the feasibility of simultaneous hydrolysis and bioconversion. Although keto-deoxy-L-galactonate accumulated intracellularly, concentrations above ~12 g l(-1) were exported to the culture supernatant. Lysis may have contributed to the release of keto-deoxy-L-galactonate from T. reesei mycelia.


Cerebrospinal fluid levels of markers of brain parenchymal damage in Vietnamese adults with severe malaria.
A retrospective study of cerebrospinal fluid (CSF) markers of brain parenchymal damage was conducted in Vietnamese adults with severe malaria. Three markers were analysed by immunoassays: the microtubule-associated protein tau, for degenerated axons; neuron-specific enolase (NSE), for neurons; and S100B for astrocytes. The mean concentration of tau proteins in the CSF was significantly raised in patients with severe malaria compared with controls (P=0.0003) as reported for other central nervous system diseases. By contrast, the mean concentration of NSE and S100B remained within the normal range. Tau levels were associated with duration of coma (P=0.004) and S100B was associated with convulsions (P=0.006). Concentrations of axonal and astrocyte degeneration markers also were associated with vital organ dysfunction. No association was found between the level of markers of brain parenchymal damage on admission and a fatal outcome. On admission to hospital, patients with severe malaria had biochemical evidence of brain parenchymal damage predominantly affecting axons.


Potential Role of Antioxidants as Adjunctive Therapy in Chagas Disease.
Chagas disease (CD) is one of the most important neglected tropical diseases in the American continent. Host-derived nitroxidative stress in response to Trypanosoma cruzi infection can induce tissue damage contributing to the progression of Chagas disease. Antioxidant supplementation has been suggested as adjuvant therapy to current treatment. In this article, we synthesize and discuss the current evidence regarding the use of antioxidants as adjunctive compounds to fight harmful reactive oxygen species and lower the tissue oxidative damage during progression of chronic Chagas disease. Several antioxidants evaluated in recent studies have shown potential benefits for the control of oxidative stress in the host's tissues. Melatonin, resveratrol, the combination of vitamin C/vitamin E (vitC/vitE) or curcumin/benznidazole, and mitochondria-targeted antioxidants seem to be beneficial in reducing plasma and cardiac levels of lipid peroxidation products. Nevertheless, further research is needed to validate beneficial effects of antioxidant therapies in Chagas disease.


Exosomes-Mediated Transfer of Itga2 Promotes Migration and Invasion of Prostate Cancer Cells by Inducing Epithelial-Mesenchymal Transition.
Although integrin alpha 2 subunit (ITGA2) mediates cancer progression and metastasis, its transfer by exosomes has not been investigated in prostate cancer (PCa). We aimed to determine the role of exosomal ITGA2 derived from castration-resistant PCa (CRPC) cells in promoting aggressive phenotypes in androgen receptor (AR)-positive cells. Exosomes were co-incubated with recipient cells and tested for different cellular assays. ITGA2 was enriched in exosomes derived from CRPC cells. Co-culture of AR-positive cells with CRPC-derived exosomes increased their proliferation, migration, and invasion by promoting epithelial-mesenchymal transition, which was reversed via ITGA2 knockdown or inhibition of exosomal uptake by methyl-β-cyclodextrin (MβCD). Ectopic expression of ITGA2 reproduced the effect of exosomal ITGA2 in PCa cells. ITGA2 transferred by exosomes exerted its effect within a shorter time compared to that triggered by its endogenous expression. The difference of ITGA2 protein expression in localized tumors and those with lymph node metastatic tissues was indistinguishable. Nevertheless, its abundance was higher in circulating exosomes collected from PCa patients when compared with normal subjects. Our findings indicate the possible role of the exosomal-ITGA2 transfer in altering the phenotype of AR-positive cells towards more aggressive phenotype. Thus, interfering with exosomal cargo transfer may inhibit the development of aggressive phenotype in PCa cells.


Dome formation by a human colonic adenocarcinoma cell line (HCA-7).
A new cell line, HCA-7, has been established from a primary human colonic adenocarcinoma. The HCA-7 cells have an epithelial morphology by phase-contrast microscopy, they secrete carcinoembryonic antigen, and they form adenocarcinomas when injected s.c. into nude mice. HCA-7 cells retain some of the morphological and functional polarity exhibited by normal colonic epithelium. Cells form a polarized epithelial sheet when grown on tissue culture plastic in standard culture medium (Dulbecco's modification of Eagle's medium with 10% fetal calf serum). The cells were shown to be structurally polarized with sparse microvilli present at the apical surface but absent from the basolateral surface. Cells were connected by apical tight junctions and frequent desmosomes. Confluent monolayers of HCA-7 cells formed "domes" or "hemicysts" due to vectorial fluid transport resulting in fluid accumulation in localized areas of the monolayer. HCA-7 cells will provide a useful system for studying the role of hormones and other factors in the control of transepithelial transport and maintenance of cell polarity.


Neuropsychiatric systemic lupus erythematosus: a diagnostic challenge.
A 58-year-old woman presented to neuropsychiatric services with increased frequency of confusional episodes and intermittent psychotic symptoms. She had a 19-year history of atypical epileptic seizures and cognitive decline. Detailed review of history and clinical investigations revealed that she had accumulated sufficient features to meet diagnostic criteria for systemic lupus erythematosus (SLE). She had previously had lymphopenia and a malar rash; she had positive antinuclear, anti-Ro (anti-Sjögren's-syndrome-related antigen A) and anti-SM (anti-Smith Antibody) antibodies, and elevated erythrocyte sedimentation rate. The seizures, cognitive impairment and psychosis were attributable to neuropsychiatric SLE. Treatment with immune-modulating therapy, cyclophosphamide, resulted in significant improvement in subjective and objective clinical presentation. Neuropsychiatric SLE should be considered a potential differential diagnosis for patients presenting with seizures, psychotic symptoms or cognitive decline. A detailed clinical evaluation with review of the medical history and appropriate laboratory analyses allows this diagnosis to be made, and appropriate treatment to be initiated.


Transcriptomic responses of juvenile Pacific whiteleg shrimp, Litopenaeus vannamei, to hypoxia and hypercapnic hypoxia.
Estuarine crustaceans are often exposed to low dissolved O2 (hypoxia) accompanied by elevated CO2 (hypercapnia), which lowers water pH. Acclimatory responses to hypoxia have been widely characterized; responses to hypercapnia in combination with hypoxia (hypercapnic hypoxia) are less well known. Here we used oligonucleotide microarrays to characterize changes in global gene expression in the hepatopancreas of Pacific whiteleg shrimp, Litopenaeus vannamei, exposed to hypoxia or hypercapnic hypoxia for 4 or 24 h, compared with time-matched animals held in air-saturated water (normoxia). Unigenes whose expressions were significantly impacted by treatment and/or time were used to build artificial neural networks (ANNs) to identify genes with the greatest sensitivity in pairwise discriminations between treatments at each time point and between times for each treatment. ANN gene sets that discriminated hypoxia or hypercapnic hypoxia from normoxia shared functions of translation, mitochondrial energetics, and cellular defense. GO terms protein modification/phosphorylation/cellular protein metabolism and RNA processing/apoptosis/cell cycling occurred at highest frequency in discriminating hypercapnic hypoxia from hypoxia at 4 and 24 h, respectively. For 75.4% of the annotated ANN genes, exposure to hypercapnic hypoxia for 24 h reduced or reversed the transcriptional response to hypoxia alone. These results suggest that high CO2/low pH may interfere with transcriptionally based acclimation to hypoxia or elicit physiological or biochemical responses that relieve internal hypoxia. Whether these data reflect resilience or sensitivity of L. vannamei in the face of expanding hypoxic zones and rising levels of atmospheric CO2 may be important to understanding the survival of this and other estuarine species.


Improving the quality of GaN crystals by using graphene or hexagonal boron nitride nanosheets substrate.
The progress in nitrides technology is widely believed to be limited and hampered by the lack of high-quality gallium nitride wafers. Though various epitaxial techniques like epitaxial lateral overgrowth and its derivatives have been used to reduce defect density, there is still plenty of room for the improvement of gallium nitride crystal. Here, we report graphene or hexagonal boron nitride nanosheets can be used to improve the quality of GaN crystal using hydride vapor phase epitaxy methods. These nanosheets were directly deposited on the substrate that is used for the epitaxial growth of GaN crystal. Systematic characterizations of the as-obtained crystal show that quality of GaN crystal is greatly improved. The fabricated light-emitting diodes using the as-obtained GaN crystals emit strong electroluminescence under room illumination. This simple yet effective technique is believed to be applicable in metal-organic chemical vapor deposition systems and will find wide applications on other crystal growth.


Pseudo-Bootstrap Network Analysis-an Application in Functional Connectivity Fingerprinting.
Brain parcellation divides the brain's spatial domain into small regions, which are represented by nodes within the network analysis framework. While template-based parcellations are widely used, the parcels on the template do not necessarily match individual's functional nodes. A new method is developed to overcome the inconsistent network analysis results by by-passing the difficulties of parcellating the brain into functionally meaningful areas. First, roughly equal-sized parcellations are obtained. Second, these random parcellations are applied to individual subjects multiple times and a pseudo-bootstrap (PBS) of the network is obtained for statistical inferences. It was found that the variation of mean global network metrics from PBS sampling is smaller compared with inter-subject variation or within-subject variation between two diffusion MRI scans. Using the mean global network metrics from PBS sampling, the intra-class correlation is always higher than the average obtained from using a single random parcellation. As one application, the PBS method was tested on the Human Connectome Project resting state dataset to identify individuals across scan sessions based on the mean functional connectivity (FC)-a trivial network property that has little information about the connectivity between nodes. An accuracy rate of ∼90% was achieved by simply finding the maximum correlation of mean FC of PBS samples between two scan sessions.


Urinary C-peptide and total triiodothyronine as energetic biomarkers for studies of lemurs.
Measuring energy balance and energy metabolism can provide crucial information for understanding the ecological and behavioral drivers of an animal's energetic and physiological condition. Both urinary C-peptide (uCP) of insulin and urinary total triiodothyronine (uTT3) have been validated as noninvasive biomarkers of energy balance and metabolic activity in haplorrhine primates. This study attempts to validate uCP and uTT3 measures in strepsirrhines, a phylogenetically distinct primate clade, using the ruffed lemur (genus Varecia) as a model. We experimentally manipulated the diet of captive black-and-white (Varecia variegata) and red (Varecia rubra) ruffed lemurs at Duke Lemur Center across a 4-week period. We collected urine samples from subjects (n = 5) each day during 1 week of control diet, 2 weeks of calorie-restricted diet and 1 week of refeeding, designed to temporarily reduce energy balance and metabolism. We also tested the outcome of filter paper as a storage method by comparing to controls (frozen at -20°C) to assess its suitability for studies of wild populations. We successfully measured uCP and uTT3 levels in frozen urine samples using commercial enzyme immunoassay kits and found that both biomarkers were excreted at lower concentrations (C-peptide: 1.35 ng/mL, 54% reduction; TT3: 1.5 ng/mL, 37.5% reduction) during calorie-restricted periods compared to normal diet periods. Filter paper recovery for uCP was 19%, though values were significantly positively correlated with frozen control samples. uTT3 could not be recovered at measurable concentrations using filter paper. These methods enable noninvasive measurement of energetic conditions in wild strepsirrhines and subsequent assessment of relationships between energy balance and numerous socioecological drivers in primate populations.


Medical students' perception of professionalism climate in clinical settings.
Medical professionalism has a crucial role in educating medical students. The role of professionalism in the clinical environment is therefore an important factor in medical education. This study attempts to evaluate the opinions of medical students in the teaching hospitals of Tehran University of Medical Sciences (TUMS) about the professionalism environment in this university. A sample of 165 students filled out the Persian translation of UMKC-SOM (Climate of Professionalism Survey) questionnaire. This instrument evaluates students' perspectives on the degree of adherence to professionalism by faculty, residents and other students. The results of the study revealed that the total score of professionalism climate was 53.9 for faculty, 42.09 for residents, and 50.76 for students and the difference between these three groups was statistically significant (p-value < 0.01). Results of further analysis through post-hoc tests for multiple comparisons among the groups revealed that the students found their fellow students and faculty more professional than residents. The study also showed that the medical ethics course had no impact on perceptions observations (p-values > 0.05). The study results also revealed that the students found their fellow students and faculty more professional than residents. This finding demonstrates the importance of teaching professionalism to residents since they serve as role models for students. Further multicenter studies are needed to improve the professionalism climate in the medical teaching environment.


New approach to vascular injection in fresh cadaver dissection.
Vascular injection techniques for anatomic studies are often complementary. Use of colored gelatinous mixtures with methylene blue provides precious data about descriptive anatomy by the contrast that it produces in the tissues. The introduction of radiopaque medium, such as lead oxide, into the gelatinous mixture can be used as a complement by means of x-ray examination, in order to facilitate and to reduce the time of investigation. Addition of rhodamine B to the radiopaque mixture keeps the advantages of the contrast medium, but also permits further dissection to demonstrate some details shown by prior x-ray examination. This article compares these different injection techniques in the study of the nasal vascular network. Moreover, it depicts a new injection approach that allows the investigation of vascular territories depending on thin caliber arteries by selective reinjection, defining microangiosomes. Each above-cited technique was used in ten facial territories of fresh cadavers. The patterns of the vessels shown by these techniques were identical, with a constant visualization of infra-millimetric arteries. However, selective reinjection was the only method that permitted characterization of the proper vascular territory of the lateral nasal artery.


Variations in intraocular pressure during closed-system surgical procedures.
True intraocular pressure (IOP) during closed-chamber anterior segment surgery and vitrectomy was measured in rabbits by inserting a miniature pressure sensor directly into the anterior chamber or into the vitreous. Infusion fluid pressure was also measured simultaneously with a sensor in the infusion line. Significant and rapid changes in IOP up to 110 mm Hg were observed during routine anterior segment and vitreous procedures. None of these IOP changes affected infusion line pressure, which was governed solely by the infusion bottle height. Furthermore, raising the infusion bottle produced minimal IOP elevation whenever fluid was flowing into and out of the eye via a surgical instrument or a wound. These results show the limitations of monitoring of infusion line pressure as a means for assessing IOP and stress the need for IOP control during surgery.


Zika Virus NS2A-Mediated Virion Assembly.
The flavivirus virion consists of an envelope outer layer, formed by envelope (E) and membrane (M) proteins on a lipid bilayer, and an internal core, formed by capsid (C) protein and genomic RNA. The molecular mechanism of flavivirus assembly is not well understood. Here, we show that Zika virus (ZIKV) NS2A protein recruits genomic RNA, the structural protein prM/E complex, and the NS2B/NS3 protease complex to the virion assembly site and orchestrates virus morphogenesis. Coimmunoprecipitation analysis showed that ZIKV NS2A binds to prM, E, NS2B, and NS3 (but not C, NS4B, or NS5) in a viral RNA-independent manner, whereas prM/E complex does not interact with NS2B/NS3 complex. Remarkably, a single-amino-acid mutation (E103A) of NS2A impairs its binding to prM/E and NS2B/NS3 and abolishes virus production, demonstrating the indispensable role of NS2A/prM/E and NS2A/NS2B/NS3 interactions in virion assembly. In addition, RNA-protein pulldown analysis identified a stem-loop RNA from the 3' untranslated region (UTR) of the viral genome as an "RNA recruitment signal" for ZIKV assembly. The 3' UTR RNA binds to a cytoplasmic loop of NS2A protein. Mutations of two positively charged residues (R96A and R102A) from the cytoplasmic loop reduce NS2A binding to viral RNA, leading to a complete loss of virion assembly. Collectively, our results support a virion assembly model in which NS2A recruits viral NS2B/NS3 protease and structural C-prM-E polyprotein to the virion assembly site; once the C-prM-E polyprotein has been processed, NS2A presents viral RNA to the structural proteins for virion assembly.IMPORTANCE ZIKV is a recently emerged mosquito-borne flavivirus that can cause devastating congenital Zika syndrome in pregnant women and Guillain-Barré syndrome in adults. The molecular mechanism of ZIKV virion assembly is largely unknown. Here, we report that ZIKV NS2A plays a central role in recruiting viral RNA, structural protein prM/E, and viral NS2B/NS3 protease to the virion assembly site and orchestrating virion morphogenesis. One mutation that impairs these interactions does not significantly affect viral RNA replication but selectively abolishes virion assembly, demonstrating the specific role of these interactions in virus morphogenesis. We also show that the 3' UTR of ZIKV RNA may serve as a "recruitment signal" through binding to NS2A to enter the virion assembly site. Following a coordinated cleavage of C-prM-E at the virion assembly site, NS2A may present the viral RNA to C protein for nucleocapsid formation followed by envelopment with prM/E proteins. The results have provided new insights into flavivirus virion assembly.


'Fly-ing' from rare to common neurodegenerative disease mechanisms.
Advances in genome sequencing have enabled researchers and clinicians to probe vast numbers of human variants to distinguish pathogenic from benign variants. Model organisms have been crucial in variant assessment and in delineating the molecular mechanisms of some of the diseases caused by these variants. The fruit fly, Drosophila melanogaster, has played a valuable role in this endeavor, taking advantage of its genetic technologies and established biological knowledge. We highlight the utility of the fly in studying the function of genes associated with rare neurological diseases that have led to a better understanding of common disease mechanisms. We emphasize that shared themes emerge among disease mechanisms, including the importance of lipids, in two prominent neurodegenerative diseases: Alzheimer's disease (AD) and Parkinson's disease (PD).


Role of cardiac, pulmonary, and carotid mechanoreceptors in the control of hind-limb and renal circulation in dogs.
Reflex control of hind-limb and renal resistance vessels by cardiac and pulmonary receptors was studied by interrupting afferent vagal nerve traffic when only the heart or only the lungs were in situ in anesthetized dogs with sinoaortic denervation. During normocapnia, interruption of cardiac and of pulmonary vagal traffic decreased hind-limb blood flow (constant-pressure perfusion) by 23% and 21%, respectively. Corresponding decreases in renal blood flow were 23% and 33%. Hypercapnia augmented the decreases in renal blood flow due to the vagal block. Thus, the inhibitions exerted by the heart and lung receptores on these two beds were similar during normocapnia but were greater on the renal vessels during hypercapnia. In closed-chest dogs with their aortic nerves sectioned and their carotid sinus pressure controlled, combined withdrawal of carotid and cardiopulmonary inhibition decreased hind-limb and renal blood flow by about 80% and 40%, respectively, during both normovolemia and hypervolemia. Interruption of cardiopulmonary inhibition was responsible for 17% and 31% of the decrease in hind-limb blood flow at normal and increased blood volumes, respectively; values for the decreases in renal blood flow were 50% and 65%. Thus, cardiopulmonary receptors oppose the vasoconstriction due to carotid hypotension more effectively in the kidney than they do in the hind limb.


@myTabu-A Placebo Controlled Randomized Trial of a Guided Web-Based Intervention for Individuals Who Sexually Abused Children and Individuals Who Consumed Child Sexual Exploitation Material: A Clinical Study Protocol.
Background: There is a high demand for evidence-based and cost-effective treatment concepts for convicted individuals who sexually abused children (ISAC) and individuals who consumed child sexual exploitation material (ICCSEM) under community supervision (CS). The @myTabu-consortium developed a guided web-based intervention for convicted ISAC and ICCSEM under CS consisting of six online modules targeting psychological meaningful risk factors. The study aims to evaluate the effectiveness of this guided web-based intervention in reducing dynamic risk factors and the risk to re-offend compared to a placebo condition. Furthermore, these dynamic risk factors are measured before and after every module to evaluate their individual effectiveness to reduce the respective risk factor as well as risk to re-offend. This clinical trial protocol describes the planned methods as well as the intervention concept. Methods: The methodological design is a placebo controlled randomized add-on trial (N = 582) with follow-ups at 8 points in time. The placebo condition controls for attention and expectation effects and comprises the same amount of modules with a comparable temporal effort as the experimental intervention. The trial is conducted as an add-on to community supervision as usually done. Primary outcomes are dynamic risk factors assessed by self-report risk assessment tools and officially recorded re-offenses. Discussion: To the best of our knowledge, the study is the first to compare the (cost-) effectiveness of a guided web-based intervention for convicted ISAC and ICCSEM under community supervision against a placebo condition. Methodological limitations (e.g., potential ceiling- or volunteers-effects) are discussed. Clinical Trial Registration: German Clinical Trial Register (DRKS 00021256). Prospectively registered: 24.04.2020.


Factors affecting outcome of patients with multiple myeloma.
Multiple myeloma is a heterogeneous disease, with wide survival range and multiple risk factors and staging systems linked to survival. The objective of this study was to assess the overall survival of patients with multiple myeloma (MM) diagnosed and treated at Shaukat Khanum Memorial Cancer Hospital (SKMCH), Lahore with respect to various prognostic factors. This was a survival analysis with data collected retrospectively on 82 patients fulfilling the diagnostic criteria of multiple myeloma. Overall survival was studied in relation to International Staging System (ISS), renal failure (Serum creatinine >2 mg/dl), anaemia (Hemoglobin <10 mg/dl), bone involvement (presence of lytic lesion on skeletal survey) and hypercalcemia (serum calcium >11mg/dl) due to multiple myeloma at the time of diagnosis. Mean age of patients was 61 years, including 67% males and 33% females. Median overall survival for ISS stage-I (24%), stage-II (44%) and stage-III (32%) was 58, 41 and 12 months respectively (p=0.01). Patients with renal impairment (16% of total) had median overall survival of 13 months compared to 41 months in patients without renal involvement (p=0.02). Hypercalcemia was noted in 27% patients with median overall survival of 32 months versus 38 months in patients without hypercalcemia, but its impact on survival was statistically insignificant (p=0.79). Similarly no significant impact on survival was noted in patients with bone involvement or anaemia found in 74 % and 38% of patient's respectively. ISS stage and renal failure due to multiple myeloma at presentation have a significant impact on survival. However, other prognostic factors like bone involvement, anaemia and hypercalcemia were not shown to influence survival significantly.


Global change and the distributional dynamics of migratory bird populations wintering in Central America.
Understanding the susceptibility of highly mobile taxa such as migratory birds to global change requires information on geographic patterns of occurrence across the annual cycle. Neotropical migrants that breed in North America and winter in Central America occur in high concentrations on their non-breeding grounds where they spend the majority of the year and where habitat loss has been associated with population declines. Here, we use eBird data to model weekly patterns of abundance and occurrence for 21 forest passerine species that winter in Central America. We estimate species' distributional dynamics across the annual cycle, which we use to determine how species are currently associated with public protected areas and projected changes in climate and land-use. The effects of global change on the non-breeding grounds is characterized by decreasing precipitation, especially during the summer, and the conversion of forest to cropland, grassland, or peri-urban. The effects of global change on the breeding grounds are characterized by increasing winter precipitation, higher temperatures, and the conversion of forest to peri-urban. During spring and autumn migration, species are projected to encounter higher temperatures, forests that have been converted to peri-urban, and increased precipitation during spring migration. Based on current distributional dynamics, susceptibility to global change is characterized by the loss of forested habitats on the non-breeding grounds, warming temperatures during migration and on the breeding grounds, and declining summer rainfall on the non-breeding grounds. Public protected areas with low and medium protection status are more prevalent on the non-breeding grounds, suggesting that management opportunities currently exist to mitigate near-term non-breeding habitat losses. These efforts would affect more individuals of more species during a longer period of the annual cycle, which may create additional opportunities for species to respond to changes in habitat or phenology that are likely to develop under climate change.


Diagnosis of Adenoid Cystic Carcinoma with Striking Tubular Hypereosinophilia by MYB and EWSR1 Breakapart Fluorescence In Situ Hybridization.
Adenoid cystic carcinoma (AdCC), associated with MYB/MYBL1 gene rearrangements, shows epithelial and basaloid myoepithelial cells arranged in tubular, cribriform and solid patterns. Variations from this classic morphology make diagnosis challenging, necessitating molecular testing. AdCC with striking tubular hypereosinophilia (AdCC-STE) is one such recently described histological subtype. A 52-year-old female presented with a floor of mouth swelling for two months, diagnosed elsewhere as polymorphous adenocarcinoma (PAC). A biopsy was obtained. With a diagnosis of oncocytic neoplasm, wide excision of the tumor was undertaken. Histological examination, fluorescence in situ hybridization (FISH) and ultrastructural examination were performed. Archival cases of PAC and epithelial myoepithelial carcinoma (EMC) were reviewed, and MYB immunostaining and FISH were performed to identify potential AdCC-STE cases. The excised tumor from the index patient showed bilayered tubules, micropapillae and cribriform pattern. Luminal cells with hypereosinophilic to clear cytoplasm were surrounded by flattened abluminal cells. Focally, basophilic matrix was seen within sharply demarcated pseudocystic spaces. FISH revealed MYB and EWSR1 gene rearrangements, confirmatory of AdCC-STE. Electron microscopy showed features consistent with AdCC; however, mitochondria were not prominent. Among 14 archival PACs, two showed MYB immunopositivity; one showed MYB rearrangement but was classical AdCC. Among 35 EMC, one case showed MYB immunoreactivity and eosinophilia of luminal cells but lacked MYB/MYBL1 rearrangement. Awareness of unusual histological subtypes of AdCC, such as AdCC-STE, is imperative, as it may be misdiagnosed as PAC and EMC, among others. Presence of basophilic matrix and squamoid morules in a biphasic tumor even with hypereosinophilic rather than basaloid myoepithelial appearance should raise suspicion for AdCC-STE, and prompt molecular testing for confirmation. With wider accessibility, lower cost and significantly shorter turn-around-time when compared to RNA sequencing, FISH can be employed for confirmation of diagnosis, especially in low- and middle-income countries.


Electrophoretic differentiaion f myofibrillar proteins in the pig.
1. Starch-gel electrophoretograms of myosin and tropomyosin preparations in 8m-urea, from longissimus dorsi and psoas muscles of the pig, were characterized by laser densitometry. 2. The typical pattern for freshly prepared myosin from both muscles was similar, there being five electrophoretically distinct components. 3. The number of electrophoretically distinct components in both muscles increased after freeze-drying, but the effect of freeze-drying was more marked in longissimus dorsi. 4. Extraction with 8m-urea containing 2% beta-mercaptoethanol decreased the number of major electrophoretically distinct components of the fresh myosin of both muscles to four. 5. Although there was also some simplification of the patterns after freeze-drying the greater susceptibility of the myosin from longissimus dorsi was still evident. 6. The typical pattern for freshly prepared tropomyosin in 8m-urea differed in the two muscles: in each case it was more complex than that of the corresponding myosins. 7. The pattern of tropomyosin from neither longissimus dorsi nor psoas was altered significantly after freeze-drying. 8. Electrophoretograms of pig longissimus dorsi tropomyosin in 8m-urea differed from those of longissimus dorsi tropomyosin from sheep, ox and rabbit. 9. Extraction of the tropomyosins in 8m-urea and 2% beta-mercaptoethanol simplified the electrophoretic pattern to two major components with samples from pig, sheep and ox, and to one major component with samples from rabbit. 10. It was concluded that classification of skeletal muscles as ;red' or ;white' is insufficient to account for the degree of functional specialization which the electrophoretograms suggest.


The role of police dogs as companions and working partners.
Written responses to a questionnaire by 255 officers who used canines in police work were assessed. Almost all officers frequently played with, talked to, petted, and brushed their dogs and believed the dogs benefitted their health and well-being. Officers whose dogs slept indoors, often in the same bedroom, generally said they loved their dogs and they described their dogs as calm rather than active, as indicated by a multiple correspondence analysis. These 96 officers more than the 154 officers whose dogs slept outdoors or in kennels also planned to remain in canine work. Although departments often assumed responsibility for purchasing the dogs, the more experienced officers usually were involved in the final selection of dogs (logistic regression: p < .0001). Compared with 94 officers not involved in selecting their dogs, 106 officers with a specific role in selecting their dogs planned to stay in canine work, as shown by a multiple correspondence analysis. They believed the dogs had saved their lives (p < .01). Over-all, officers reported spending 4.1 hr. on-duty and 2.9 hr. off-duty per week training their dogs, and also played with them for 6.5 hr. per week, assuring a regular pattern of exercise for the officers. Virtually all officers valued canine service and believed the dogs enhanced the department's effectiveness. This study showed that both close companionship with the dog and involvement in selecting the dog were associated both with satisfaction with the dog and with working as a canine officer.


Diabetic therapeutic effects of ethyl acetate fraction from the roots of Musa paradisiaca and seeds of Eugenia jambolana in streptozotocin-induced male diabetic rats.
The folklore medicine of primitive people has been greatly appreciated for centuries. Many researchers study the curative efficiency and mode of action of various medicinal plants. Serum glucose level, lipid profile, glucose tolerance, hepatic and muscle glycogen contents as well as the activities of hepatic hexokinase and glucose-6-phosphatase recovered significantly after oral administration of ethyl acetate fractions of Eugenia jambolana (E. jambolana) or Musa paradisiaca (M. paradisiaca) in separate (E. jambolana L.: 200 mg/kg of body weight and M. paradisiaca: 100 mg/kg of body weight) or combined form for 90 days (twice a day through gavage) to streptozotocin-induced diabetic rats. The loss in body weight of diabetic animals was reversed and serum levels of insulin as well as C-peptide, which were found to be reduced in diabetic rats, increased significantly after oral administration of the fractions. A histological study of the rats' pancreas revealed that after 90 days of oral treatment with the plant fractions in separate or combined form, the size and volume of pancreatic islets in diabetic treated rats increased significantly compared with the diabetic control group. Treatment of diabetic rats with the combined dose (300 mg/kg of body weight) of plant fractions (200 mg E. jambolana and 100 mg M. paradisiaca) was found to be more effective than treatment with the individual fraction. The doses of E. jambolana and M. paradisiaca selected for this study are the optimum antihyperglycemic doses of the plant fractions, which were determined after conducting a dose-dependent study at various dose levels (50-500 mg/kg) in our pilot experiments. The plant fractions were found to be free from metabolic toxicity. Through HPTLC finger printing, three different compounds were noted in the ethyl acetate fraction of E. jambolana L. and eight different compounds in the ethyl acetate fraction of M. paradisiaca L.


Ethnoveterinary Survey of Medicinal Plants Used for Treatment of Animal Diseases in Ambo District of Oromia Regional State of Ethiopia.
Traditional knowledge on the use of medicinal plants is in danger of extinction because of different changes taking place all over the world including Ethiopia, and thus, there is a need for its immediate documentation for the purpose of conservation, sustainable utilization, and development. Thus, an ethnobotanical study was conducted in Ambo District, Oromia Regional State of Ethiopia, to document and analyze local knowledge on medicinal plants used for the treatment of animal diseases. Data were collected between November 2017 and April 2018 mainly through semi-interviews conducted with purposively selected informants. Data collected mainly included demographic information of respondents, local names of medicinal plants, plant parts used, preparation methods, mode of applications, diseases treated, and habit and habitat of the reported plants. Based on data obtained through interviews, informant consensus factor (ICF) values were computed. A total of 55 medicinal plants used to manage livestock ailment were reported by informants in the Ambo District. Herbs were commonly used in the preparation of remedies. Leaf was the most frequently utilized plant part accounting for 49.1% of the total reported medicinal plants. The majority (69.0%) of the medicinal plants used in the study district were uncultivated ones mainly harvested from edges of forests and bushlands, roadsides, riverbanks, and grasslands. High ICF values were obtained for ophthalmological (0.82), dermatological (0.79), febrile (0.77), and gastrointestinal ailments (0.77). The current study shows that there is still rich traditional knowledge on the use of plants to control various animal diseases in the study district. However, such a claim needs to be scientifically verified with priority given to medicinal plants used in the treatment of ailment categories with high ICF values as such plants are considered to be good candidates for further pharmacological evaluation.


Deblocking of block-transform compressed images using weighted sums of symmetrically aligned pixels.
A new class of related algorithms for deblocking block-transform compressed images and video sequences is proposed in this paper. The algorithms apply weighted sums on pixel quartets, which are symmetrically aligned with respect to block boundaries. The basic weights, which are aimed at very low bit-rate images, are obtained from a two-dimensional function which obeys predefined constraints. Using these weights on images compressed at higher bit rates produces a deblocked image which contains blurred "false" edges near real edges. We refer to this phenomenon as the ghosting effect. In order to prevent its occurrences, the weights of pixels, which belong to nonmonotone areas, are modified by dividing each pixel's weight by a predefined factor called a grade. This scheme is referred to as weight adaptation by grading (WABG). Better deblocking of monotone areas is achieved by applying three iterations of the WABG scheme on such areas followed by a fourth iteration which is applied on the rest of the image. We refer to this scheme as deblocking frames of variable size (DFOVS). DFOVS automatically adapts itself to the activity of each block. This new class of algorithms produces very good subjective results and PSNR results which are competitive relative to available state-of-the-art methods.


A Markov-blanket-based model for gene regulatory network inference.
An efficient two-step Markov blanket method for modeling and inferring complex regulatory networks from large-scale microarray data sets is presented. The inferred gene regulatory network (GRN) is based on the time series gene expression data capturing the underlying gene interactions. For constructing a highly accurate GRN, the proposed method performs: 1) discovery of a gene's Markov Blanket (MB), 2) formulation of a flexible measure to determine the network's quality, 3) efficient searching with the aid of a guided genetic algorithm, and 4) pruning to obtain a minimal set of correct interactions. Investigations are carried out using both synthetic as well as yeast cell cycle gene expression data sets. The realistic synthetic data sets validate the robustness of the method by varying topology, sample size, time delay, noise, vertex in-degree, and the presence of hidden nodes. It is shown that the proposed approach has excellent inferential capabilities and high accuracy even in the presence of noise. The gene network inferred from yeast cell cycle data is investigated for its biological relevance using well-known interactions, sequence analysis, motif patterns, and GO data. Further, novel interactions are predicted for the unknown genes of the network and their influence on other genes is also discussed.


Renal transplantation in autosomal dominant polycystic kidney disease.
In patients with autosomal dominant polycystic kidney disease (ADPKD) evaluated for kidney transplantation, issues related to native nephrectomy, cystic liver involvement, screening for intracranial aneurysms and living-related kidney donation deserve special consideration. Prophylactic native nephrectomy is restricted to patients with a history of cyst infection or recurrent haemorrhage or to those in whom space must be made to implant the graft. Patients with liver involvement require pretransplant imaging. Selection of patients for pretransplant screening of intracranial aneurysms should follow the general recommendations for patients with ADPKD. In living related-donor candidates aged <30 years and at-risk of ADPKD, molecular genetic testing should be carried out when ultrasonography and MRI findings are normal or equivocal. After kidney transplantation, patient and graft survival rates are excellent and the volume of native kidneys decreases. However, liver cysts continue to grow and treatment with a somatostatin analogue should be considered in patients with massive cyst involvement. Cerebrovascular events have a marginal effect on post-transplant morbidity and mortality. An increased risk of new-onset diabetes mellitus and nonmelanoma skin cancers has been reported, but several studies have challenged these findings. Finally, no data currently support the preferential use of mammalian target of rapamycin inhibitors as immunosuppressive agents in transplant recipients with ADPKD.


Decisional balances and the process of change in smoking cessation in patients with coronary artery diseases.
Despite many smoking cessation programs, many patients with CAD continue to smoke or re-smoke. The processes of change and self-change for smoking cessation is emphasized. The purpose of present study was to investigate decisional balances and processes of change according to stages of change for smoking cessation in the patients with CAD. This descriptive study was performed using the self-reported questionnaires from 157 male patients with CAD who have smoking experiences. The questionnaires consisted of decisional balances toward smoking (pros/cons) and processes of change including 7 factors. 45.2% of the subjects had myocardial infarction and 54.8% for angina pectoris. Major stages of change were maintenance, contemplation, and precontemplation in 62%, 14%, and 18% respectively. The mean score of pros smoking was 31.07 and cons smoking was 32.52. The mean scores of processes of change were high in all 7 factors, especially in self determination. The pros smoking in precontemplation stage was significantly higher than those in other stages. Between contemplation and precontemplation stages, processes of change showed significant differences in stimulus control, self determination, information management, and dramatic relief. This study suggests that decisional balances and processes of change are stage-specific. As this study, smoking cessation program in the patients with CAD must put priority on the patients group in precontemplation and contemplation stages, and stress self determination and dramatic relief.