Evaluation of the Antioxidant Activity of Extracts and Active Principles of Commonly Consumed Indian Spices.
Accumulating evidence suggests that free radical reactions play a key part in the development of degenerative diseases and that an antioxidant-rich diet is a major defense against these free radical reactions. In this study, we explore comparative antioxidant capacities of extracts of some commonly used in Indian spices (anise, cardamom, Ceylon cinnamon, and clove) along with their purified components (anethole, eucalyptol, cinnamaldehyde, and eugenol, respectively). Eugenol shows the highest 1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and superoxide scavenging and reducing power activity in terms of weight; however, this was not found when compared in terms of equivalence. Extracts of the other three spices were found to be more potent antioxidants than their corresponding active components. Interestingly, clove extract, despite possessing the highest phenol and flavonoid content, is not the most potent radical scavenger. At low concentrations, both the crude extracts and their purified components (except for anethole and eugenol) have low hemolytic activity, but at higher concentrations purified components are more toxic than their respective crude extract. This study suggests that spices as a whole are more potent antioxidants than their purified active components, perhaps reflecting the synergism among different phytochemicals present in spice extracts.


Control of gamete formation (exflagellation) in malaria parasites.
The only stages of malaria parasites capable of establishing an infection in a mosquito are the gametocytes that circulate in the blood of the veterbrate host. Within minutes of ingestion by a mosquito the gametocytes transform into mature gametes in the process of "exflagellation." This process is controlled in vitro solely by the change in pH in the blood as it moves from the environment of the circulation to that of the atmosphere, the pH rise being mediated by the fall in carbon dioxide tension as the blood equilibrates with the atmosphere.


Undetermined cause and manner of death after organ/tissue donation.
The Harris County Medical Examiner's Office (HCME) is proactive and supportive with regard to organ and tissue donation. Steps taken to facilitate donation include development of standardized multiagency protocols for organ/tissue requests and transfer of decedents out of the facility for tissue recovery prior to autopsy. The organ/tissue agencies have 24-hour access to a liaison staff member. No blanket denials are issued for any case type; instead each case is evaluated for feasibility of donation. In rare instances donation of one or more organs is considered detrimental to the mission of determining cause and manner of death. In these cases, the HCME requests that specific organ(s) not be recovered. In this jurisdiction, the organ procurement organization often proceeds with organ recovery despite medical examiner objection. In such cases, the autopsy examination is incomplete and the cause of death cannot be determined. A series of 5 organ donation cases are presented for illustration. Four of these cases are infant deaths in which the HCME requested specific organs not be donated. In the fifth case no denial was issued, but release was granted on incomplete or erroneous information. The cause and manner of death in each case remains undetermined.


Exposure assessment in different occupational groups at a hospital using Quick Exposure Check (QEC) - a pilot study.
In order to test the feasibility and sensitivity of the ergonomic exposure assessment tool Quick Exposure Check (QEC), a pilot-study was conducted. The aim was to test QEC in different occupational groups to compare the exposure in the most common work task with the exposure in the work task perceived as the most strenuous for the neck/shoulder region, and to test intra-observer reliability. One experienced ergonomist observed 23 workers. The mean observation time was 45 minutes, waiting time and time for complementary questions included. The exposure scores varied between the different occupational groups as well as between workers within the occupational groups. Eighteen workers rated their most common work task as also being the most strenuous for the neck/shoulder region. For the remaining five workers, the mean exposure score were higher both for the neck and shoulder/arm in the most common work task. Intra-observer reliability shows agreement in 86% of the exposure interactions in the neck and in 71% in the shoulder/arm. QEC seems to fulfill the expectations of being a quick, sensible and practical exposure assessment tool that covers physical risk factors in the neck, upper extremities and low back.


Between the Balkans and the Baltic: Phylogeography of a Common Vole Mitochondrial DNA Lineage Limited to Central Europe.
The common vole (Microtus arvalis) has been a model species of small mammal for studying end-glacial colonization history. In the present study we expanded the sampling from central and eastern Europe, analyzing contemporary genetic structure to identify the role of a potential 'northern glacial refugium', i.e. a refugium at a higher latitude than the traditional Mediterranean refugia. Altogether we analyzed 786 cytochrome b (cytb) sequences (representing mitochondrial DNA; mtDNA) from the whole of Europe, adding 177 new sequences from central and eastern Europe, and we conducted analyses on eight microsatellite loci for 499 individuals (representing nuclear DNA) from central and eastern Europe, adding data on 311 new specimens. Our new data fill gaps in the vicinity of the Carpathian Mountains, the potential northern refugium, such that there is now dense sampling from the Balkans to the Baltic Sea. Here we present evidence that the Eastern mtDNA lineage of the common vole was present in the vicinity of this Carpathian refugium during the Last Glacial Maximum and the Younger Dryas. The Eastern lineage expanded from this refugium to the Baltic and shows low cytb nucleotide diversity in those most northerly parts of the distribution. Analyses of microsatellites revealed a similar pattern but also showed little differentiation between all of the populations sampled in central and eastern Europe.


Regulation of antibody production by an antigen-specific EBV-transformed B-lymphoblastoid cell line: effect of high-dose antigen and antigen-pulsed T cells.
A B-cell line (C1B2) secreting monoclonal IgG antibody to influenza virus haemagglutinin (HA3) was obtained by Epstein-Barr virus (EBV) transformation of human tonsillar B cells activated in vitro to influenza A/X31. Antibody secretion by C1B2 was completely inhibited by purified HA3 at concentrations above 100 ng/ml. By contrast, high doses of HA3 had no effect on EBV-transformed B-cell lines making antibody of unrelated specificity. Inhibition of specific antibody secretion by HA3 continued for at least 3 days after the removal of soluble antigen, but this could be partially reversed by treatment with pronase, suggesting that inhibition was due to 'effector cell' blockade by binding of antigen to surface Ig receptors. T cells pulsed with high doses of antigen also suppressed antibody secretion by C1B2, but this effect was probably due to a tolerogenic signal delivered to the B cell by HA3 complexed to the T-cell membrane rather than suppression by antigen-induced Ts, or carryover of free antigen. These experiments demonstrate two independent mechanisms of high-dose tolerance in vitro, and show that monoclonal B-lymphoblastoid lines of known specificity can be used to study regulation of specific antibody production at the level of the B cell.


Effectiveness of dry needling techniques in patients with knee osteoarthritis: A systematic review and meta-analysis.
Dry needling has been found to be effective in various myofascial pain syndromes and musculoskeletal conditions. However, there is a need to evaluate the effects of dry needling techniques in patients with knee osteoarthritis. Hence, the objective of this systematic review was to identify and critically review the evidence on the short-term and long-term effects of dry needling techniques in patients with knee osteoarthritis. Databases such as Pubmed, Cochrane library, and Scopus were searched from their inception to July 2019 for randomized controlled trials using dry needling as an active intervention against control/sham/placebo treatment in patients with knee osteoarthritis. The quality of the selected studies was analyzed using Cochrane tool for assessment of risk of bias. Out of 247 studies, 9 studies were included in the review. The qualitative synthesis for myofascial trigger point dry needling showed contradictory results. The mean difference for periosteal stimulation was significant on pain and function immediately post-treatment (p < 0.00001). The mean difference for intramuscular electrical stimulation on pain was significant (p = 0.03), but marked heterogeneity was found among the studies. Good quality studies on myofascial trigger point needling and intramuscular electrical stimulation are required to evaluate their effects in patients with knee osteoarthritis. The review demonstrates a moderate-quality evidence on the short-term effect of periosteal stimulation technique on pain and function in knee osteoarthritis. Future studies comparing the effects of various techniques of dry needling with different dosages and long-term follow up need to be conducted.


Diagnosis of nail psoriasis: evaluation of nail-derived microRNAs as potential novel biomarkers.
MicroRNA levels in sera or hair may potentially be useful biomarkers for various diseases. The diagnosis of nail diseases is sometimes difficult, and nail psoriasis without skin lesions is indistinguishable from nail changes caused by other diseases. We evaluated nail microRNA levels as biomarkers for the diagnosis of psoriasis patients. MicroRNA levels were examined in psoriasis patients with (11 patients) and without (six patients) nail changes. Normal control nails were collected from 17 healthy subjects. Eight patients with other diseases who also had nail changes were also included as disease controls. Microarray, real-time PCR, and in situ hybridisation indicated that the expression levels of nail miR-4454 were decreased in psoriasis patients with nail changes, compared to those patients with other diseases involving nail change, or healthy subjects. The miR-4454 levels in nails showed a significant inverse correlation with the Nail Psoriasis Severity Index (NAPSI) score, suggesting that nail miR-4454 levels reflect nail condition. The levels of microRNAs in nails may be suitable biomarkers for diagnosis or evaluation of disease activity of psoriasis.


A giant exoplanet orbiting a very-low-mass star challenges planet formation models.
Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.


Inhibition of yes-associated protein down-regulates PD-L1 (CD274) expression in human malignant pleural mesothelioma.
Although tumour PD-L1 (CD274) expression had been used as a predictive biomarker in checkpoint immunotherapy targeting the PD1/PD-L1 axis in various cancers, the regulation of PD-L1 (CD274) expression is unclear. Yes-associated protein (YAP), an important oncogenic protein in Hippo signalling pathway, reportedly promotes cancer development. We investigated whether inhibition of YAP down-regulates PD-L1 (CD274) in human malignant pleural mesothelioma (MPM). Western blotting showed that 2 human MPM cell lines (H2052 and 211H) had increased PD-L1 protein expression compared to H290, MS-1 and H28 cells. In H2052 and 211H cells, PD-L1 mRNA expression was significantly increased compared to other MPM cell lines; YAP knockdown by small interfering RNA decreased PD-L1 protein and mRNA expression. Forced overexpression of the YAP gene increased PD-L1 protein expression in H2452 cells. Chromatin immunoprecipitation (ChIP) assay showed the precipitation of PD-L1 enhancer region encompassing 2 putative YAP-TEAD-binding sites in H2052 cells. We found that, in human MPM tissue microarray samples, YAP and PD-L1 concurrently expressed in immunohistochemistry stain (n = 70, P < .05, chi-square). We conclude that PD-L1 is correlated with YAP expression, and inhibition of YAP down-regulates PD-L1 expression in human MPM. Further study of how YAP regulates PD-L1 in MPM is warranted.


Intermittent fasting modulation of the diabetic syndrome in sand rats. III. Post-mortem investigations.
The present report concerns several post-mortem variables examined in sand rats that were either maintained on a vegetal diet (control animals) or exposed first during a 20-day transition period to a mixed diet consisting of a fixed amount of a hypercaloric food and decreasing amounts of the vegetal food and then to a 30-day experimental period of exposure to the hypercaloric food. During the latter period, all animals were either given free access to food or fasting daily for 15 h, i.e. from 5.00 p.m. to 8.00 a.m. The body weight, liver wet weight, pancreas wet weight, plasma glucose and haemoglobin A1c concentration, plasma insulin concentration, insulinogenic index, insulin resistance HOMA, plasma cholesterol and triglyceride concentration, liver triglyceride and phospholipid content were all measured. Pancreatic islet (insulin, GLUT2) and liver (lipid droplets) histology were also examined. The main findings consisted in a lower body weight of fasting than non-fasting animals, a higher liver weight in non-diabetic and diabetic rats than in control non-fasting (but not so in fasting) animals, a decrease of pancreas weight in non-diabetic and diabetic as distinct from control animals, a fasting-induced decrease in plasma glucose, plasma insulin and insulin resistance HOMA, plasma cholesterol and triglyceride concentration and triglyceride liver content.


Titin-isoform dependence of titin-actin interaction and its regulation by S100A1/Ca2+ in skinned myocardium.
Titin, also known as connectin, is a large filamentous protein that greatly contributes to passive myocardial stiffness. In vitro evidence suggests that one of titin's spring elements, the PEVK, interacts with actin and that this adds a viscous component to passive stiffness. Differential splicing of titin gives rise to the stiff N2B and more compliant N2BA isoforms. Here we studied the titin-isoform dependence of titin-actin interaction and studied the bovine left atrium (BLA) that expresses mainly N2BA titin, and the bovine left ventricle (BLV) that expresses a mixture of both N2B and N2BA isoforms. For comparison we also studied mouse left ventricular (MLV) myocardium which expresses predominately N2B titin. Using the actin-severing protein gelsolin, we obtained evidence that titin-actin interaction contributes significantly to passive myocardial stiffness in all tissue types, but most in MLV, least in BLA, and an intermediate level in BLV. We also studied whether titin-actin interaction is regulated by S100A1/calcium and found that calcium alone or S100A1 alone did not alter passive stiffness, but that combined they significantly lowered stiffness. We propose that titin-actin interaction is a "viscous break" that is on during diastole and off during systole.


Inter-cluster distance dependence of electrical properties in single crystals of a mixed-valence polyoxometalate.
The electrical conductivity of mixed-valence [MoMoO54(SO3)2]6- tetraalkylammonium salts was investigated through dependence on the inter-cluster distance that is controlled by tetraethylammonium, tetrapropylammonium, and tetrabutylammonium cations. The crystallographic analysis of single crystals revealed that the inter-cluster distances are dependent on the chain length of the alkyl groups on the counter cations. In addition, the electrical conductivities of the single crystals were found to be dependent on both temperature and chain length. Mixed-valence polyoxometalate (POM) clusters are considered to be a molecular particle of Mo bronze by which highly ordered networks will be developed using single crystals, where POMs are rather small and have a well-organized structure compared to colloidal nanostructures.


Closed-Locked and Apo-Resting State Structures of the Human α7 Nicotinic Receptor: A Computational Study.
Nicotinic acetylcholine receptors, belonging to the Cys-loop superfamily of ligand-gated ion channels (LGICs), are membrane proteins present in neurons and at neuromuscular junctions. They are responsible for signal transmission, and their function is regulated by neurotransmitters, agonists, and antagonists drugs. A detailed knowledge of their conformational transition in response to ligand binding is critical to understanding the basis of ligand-receptor interaction, in view of new pharmacological approaches to control receptor activity. However, the scarcity of experimentally derived structures of human channels makes this perspective extremely challenging. To contribute overcoming this issue, we have recently reported structural models for the open and the desensitized states of the human α7 nicotinic receptor. Here, we provide all-atom structural models of the same receptor in two different nonconductive states. The first structure, built via homology modeling and relaxed with extensive Molecular Dynamics simulations, represents the receptor bound to the natural antagonist α-conotoxin ImI. After comparison with available experimental data and computational models of other eukaryotic LGICs, we deem it consistent with the "closed-locked" state. The second model, obtained with simulations from the spontaneous relaxation of the open, agonist-bound α7 structure after ligand removal, recapitulates the characteristics of the apo-resting state of the receptor. These results add to our previous work on the active and desensitized state conformations, contributing to the structural characterization of the conformational landscape of the human α7 receptor and suggesting benchmarks to discriminate among conformations found in experiments or in simulations of LGICs. In particular key interactions at the interface between the extracellular domain and the transmembrane domain are identified, that could be critical to the α7 receptor function.


Prefrontal brain responsiveness to negative stimuli distinguishes familial risk for major depression from acute disorder.
Identifying reliable trait markers of familial risk for major depressive disorder (MDD) is a challenge in translational psychiatric research. In individuals with acute MDD, dysfunctional connectivity patterns of prefrontal areas have been shown repeatedly. However, it has been unclear in which neuronal networks functional alterations in individuals at familial risk for MDD might be present and to what extent they resemble findings previously reported in those with acute MDD. We investigated differences in blood oxygen level-dependent (BOLD) response of the medial orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) to aversive stimuli between acute MDD and familial risk for the disorder in healthy first-degree relatives of acutely depressed patients with MDD (HC-FH+), healthy age- and sex-matched controls without any family history of depression (HC-FH-), and acutely depressed patients with MDD with (MDD-FH+) and without a family history of depression (MDD-FH-) during a frequently used emotional face-matching paradigm. Analyses of task-specific network connectivity were conducted in terms of psychophysiological interactions (PPI). The present analysis included a total of 100 participants: 25 HC-FH+, 25 HC-FH-, 25 MDD-FH+ and 25 MDD-FH-. Patients with MDD exhibited significantly increased activation in the medial OFC to negative stimuli irrespective of familial risk status, whereas healthy participants at familial risk and patients with MDD alike showed significant hypoactivation in the DLPFC compared with healthy participants without familial risk. The PPI analyses revealed significantly enhanced task-specific coupling between the medial OFC and differing cortical areas in individuals with acute MDD and those with familial risk for the disorder. The main limitation of our study is its cross-sectional design. Whereas hypoactivation during negative emotion processing in the DLPFC appears as a common feature in both healthy high-risk individuals and acutely depressed patients, activation patterns of the medial OFC and its underlying connectivity seem to distinguish familial risk from acute disorder.


Disease-Free Survival for Patients with Thin Melanomas according to the American Joint Committee on Cancer 8th Edition.
The recently implemented AJCC 8th edition TNM staging system for malignant melanoma (MM) changed the definition for T1a and T1b tumours. To analyse differences in disease-free survival (DFS) among patients with thin MM staged according to both AJCC 7th and 8th editions. An observational study including 285 patients with cutaneous thin MM (thickness ≤1 mm). Cases were staged as T1a and T1b using both 7th and 8th editions. Neither regional nor visceral diseases were present at diagnosis. DFS curves were generated according to the Kaplan-Meier method. An 8% shift of patients from a T1a towards a T1b stage group was observed after applying the AJCC 8th edition. According to this 8th edition, DFS for T1a patients was significantly longer than for T1b patients (log-rank test; p = 0.005); 5-year DFS for T1a and T1b was 100 and 95%, respectively (Wilcoxon test; p = 0.002). According to the AJCC 7th edition, DFS did not significantly differ for T1a and T1b patients; 5-year DFS for T1a and T1b was 99 and 97%, respectively (p > 0.05). The AJCC 8th edition seems to be a better tool for staging thin melanomas.


Evolution in the fast lane: rapidly evolving sex-related genes in Drosophila.
A large portion of the annotated genes in Drosophila melanogaster show sex-biased expression, indicating that sex and reproduction-related genes (SRR genes) represent an appreciable component of the genome. Previous studies, in which subsets of genes were compared among few Drosophila species, have found that SRR genes exhibit unusual evolutionary patterns. Here, we have used the newly released genome sequences from 12 Drosophila species, coupled to a larger set of SRR genes, to comprehensively test the generality of these patterns. Among 2505 SRR genes examined, including ESTs with biased expression in reproductive tissues and genes characterized as involved in gametogenesis, we find that a relatively high proportion of SRR genes have experienced accelerated divergence throughout the genus Drosophila. Several testis-specific genes, male seminal fluid proteins (SFPs), and spermatogenesis genes show lineage-specific bursts of accelerated evolution and positive selection. SFP genes also show evidence of lineage-specific gene loss and/or gain. These results bring us closer to understanding the details of the evolutionary dynamics of SRR genes with respect to species divergence.


Educators' Views on Using Humanoid Robots With Autistic Learners in Special Education Settings in England.
Researchers, industry, and practitioners are increasingly interested in the potential of social robots in education for learners on the autism spectrum. In this study, we conducted semi-structured interviews and focus groups with educators in England to gain their perspectives on the potential use of humanoid robots with autistic pupils, eliciting ideas, and specific examples of potential use. Understanding educator views is essential, because they are key decision-makers for the adoption of robots and would directly facilitate future use with pupils. Educators were provided with several example images (e.g., NAO, KASPAR, Milo), but did not directly interact with robots or receive information on current technical capabilities. The goal was for educators to respond to the general concept of humanoid robots as an educational tool, rather than to focus on the existing uses or behaviour of a particular robot. Thirty-one autism education staff participated, representing a range of special education settings and age groups as well as multiple professional roles (e.g., teachers, teaching assistants, speech, and language therapists). Thematic analysis of the interview transcripts identified four themes: Engagingness of robots, Predictability and consistency, Roles of robots in autism education, and Need for children to interact with people, not robots. Although almost all interviewees were receptive toward using humanoid robots in the classroom, they were not uncritically approving. Rather, they perceived future robot use as likely posing a series of complex cost-benefit trade-offs over time. For example, they felt that a highly motivating, predictable social robot might increase children's readiness to learn in the classroom, but it could also prevent children from engaging fully with other people or activities. Educator views also assumed that skills learned with a robot would generalise, and that robots' predictability is beneficial for autistic children-claims that need further supporting evidence. These interview results offer many points of guidance to the HRI research community about how humanoid robots could meet the specific needs of autistic learners, as well as identifying issues that will need to be resolved for robots to be both acceptable and successfully deployed in special education contexts.


Immobilization of laccase by encapsulation in a sol-gel matrix and its characterization and use for the removal of estrogens.
Laccase from Myceliophthora thermophila was immobilized by encapsulation in a sol-gel matrix based on methyltrimethoxysilane and tetramethoxysilane. The amount of laccase used for the preparation of the hydrogel was in the range 2.2-22 mg of protein/mL sol and the corresponding enzymatic activities were in the range 5.5-17.0 U/g biocatalyst. The kinetic parameters of the encapsulated laccase showed that the immobilized enzyme presented lower affinity for the substrate 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS). However, the stability of laccase was significantly enhanced after immobilization; thus, both pH and thermal stability improved about 10-30% and tolerance to different inactivating agents (NaN(3) , ZnCl(2) , CoCl(2) , CaCl(2) , methanol, and acetone) was 20-40% higher. The reusability of the immobilized laccase was demonstrated in the oxidation of ABTS for several consecutive cycles, preserving 80% of the initial laccase activity after 10 cycles. The feasibility of the immobilized biocatalyst was tested for the continuous elimination of Acid Green 27 dye as a model compound in a packed-bed reactor (PBR). Removals of 70, 58, 57, and 55% were achieved after four consecutive cycles with limited adsorption on the support: only 10-15%. Finally, both batch stirred tank reactor (BSTR) operated in several cycles and PBR, containing the solid biocatalyst were applied for the treatment of a solution containing the endocrine disrupting chemicals (EDCs): estrone (E1), 17β-estradiol (E2), and 17α-ethinylestradiol (EE2). Eliminations of EDCs in the BSTR were higher than 85% and the reusability of the biocatalyst for the degradation of those estrogens was demonstrated. In the continuous operation of the PBR, E1 was degraded by 55% and E2 and EE2 were removed up to 75 and 60%, at steady-state conditions. In addition, a 63% decrease in estrogenic activity was detected.


Systematic review of the global epidemiology, clinical and laboratory profile of enteric fever.
Children suffer the highest burden of enteric fever among populations in South Asian countries. The clinical features are non-specific, vary in populations, and are often difficult to distinguish clinically from other febrile illnesses, leading to delayed or inappropriate diagnosis and treatment. We undertook a systematic review to assess the clinical profile and laboratory features of enteric fever across age groups, economic regions, level of care and antibiotic susceptibility patterns. We searched PubMed (January 1964-December 2013) for studies describing clinical features in defined cohorts of patients over varying time periods. Studies with all culture-confirmed cases or those with at least 50% culture-confirmed cases were included. 242 reports were screened out of 4398 relevant articles and 180 reports were included for final review. 96% of studies were from an urban location, 96% were hospital-based studies, with 41% of studies were from South Asia. Common clinical features in hospitalized children include high-grade fever, coated tongue, anaemia, nausea/vomiting, diarrhea, constipation, hepatomegaly, splenomegaly neutrophilia, abdominal distension and GI bleeding. In adults' nausea/vomiting, thrombocytopenia and GI perforation predominate. The case-fatality rate in children under 5 years is higher than school aged children and adolescents, and is highest in Sub Saharan Africa and North Africa/Middle East regions. Multi-drug resistant enteric fever has higher rates of complications than drug sensitive enteric fever, but case fatality rates were comparable in both. Our findings indicate variability in disease presentation in adults compared to children, in different regions and in resistant vs sensitive cases. Majority of studies are from hospitalized cases, and are not disaggregated by age. Despite higher complications in MDR enteric fever, case fatality rate is comparable to sensitive cases, with an overall hospital based CFR of 2%, which is similar to recent global estimates. This review underscores the importance of further epidemiological studies in community settings among children and adults, and the need for further preventable measures to curtail the burden of disease.


Cell interactions between histoincompatible T and B lymphocytes. VII. Cooperative responses between lymphocytes are controlled by genes in the I region of the H-2 complex.
The results of this study provide compelling evidence for the existence of the gene or genes controlling optimal T-B-cell cooperative interactions in the designated I region of the H-2 gene complex. Previously, we have speculated that the relevant gene(s) involved may well be located in this region based on several observations from our earlier work in this area (3, 5, 6). Thus, in the preceding paper, we showed that T and B cells from B10.BR and A strain mice developed effective cooperative interactions in vitro to DNP-KLH in a system identical to the one reported herein. Since these mice differ for genes in the S and D regions of H-2 but are identical for K and I region genes, we were able to localize the critical genes to the K-end of H-2.


Impact of Obesity on Pediatric Acute Recurrent and Chronic Pancreatitis.
The aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP). We determined body mass index (BMI) status at enrollment in INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort using CDC criteria for pediatric-specific BMI percentiles. We used the Cochran-Armitage test to assess trends and the Jonckheere-Terpstra test to determine associations. Of 446 subjects (acute recurrent pancreatitis, n = 241; CP, n = 205), 22 were underweight, 258 normal weight, 75 overweight, and 91 were obese. The BMI groups were similar in sex, race, and age at presentation. Hypertriglyceridemia was more common in overweight or obese. Obese children were less likely to have CP and more likely to have acute inflammation on imaging. Compared with children with normal weight, obese or overweight children were older at first acute pancreatitis episode and diagnosed with CP at an older age. Obese or overweight children were less likely to undergo medical or endoscopic treatment, develop exocrine pancreatic insufficiency, and require total pancreatectomy with islet autotransplantation. Diabetes was similar among all groups. Obesity or overweight seems to delay the initial acute pancreatitis episode and diagnosis of CP compared with normal weight or underweight. The impact of obesity on pediatric CP progression and severity deserves further study.


Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number.
In the mammalian nervous system, neuronal activity regulates the strength and number of synapses formed. The genetic program that coordinates this process is poorly understood. We show that myocyte enhancer factor 2 (MEF2) transcription factors suppressed excitatory synapse number in a neuronal activity- and calcineurin-dependent manner as hippocampal neurons formed synapses. In response to increased neuronal activity, calcium influx into neurons induced the activation of the calcium/calmodulin-regulated phosphatase calcineurin, which dephosphorylated and activated MEF2. When activated, MEF2 promoted the transcription of a set of genes, including arc and synGAP, that restrict synapse number. These findings define an activity-dependent transcriptional program that may control synapse number during development.


Reproductive outcomes after medical and surgical management of ectopic pregnancy.
Ectopic pregnancies have a negative impact on future fertility. Prompt diagnosis is paramount to preserve tubal function and reproductive potential. Expectant, medical, and surgical management of ectopic pregnancies have similar efficacy in properly selected patients. Medical management has emerged as a safe alternative to surgery and holds promise for preservation of future fertility. Laparoscopic salpingostomy or salpingectomy remains the preferred means of surgical removal of ectopic pregnancies. The most predictive factor of future fertility is the health of the contralateral tube.


Proinsulin: metabolic effects in the human forearm.
Five subjects were studied by the forearm perfusion technique with proinsulin at a final plasma conceintration of 1.76 x 10(-9) millimole per milliliter. Two of these subjects were studied with single-component insulin at a concentration of 1.96 x 10(-9) millimole per milliliter. Proinsulin is, in general, biologically less potent than single-component insulin. In contrast to insulin, its effects upon adipose tissue are for the most part greater than upon muscle.


Development and validation of the Adolescent Asthma Self-Efficacy Questionnaire (AASEQ).
Perceived self-efficacy is the belief that one can manage prospective situations. Good asthma self-management self-efficacy is associated with better asthma outcomes. However, a well-developed and validated tool to measure adolescent asthma self-management self-efficacy is lacking. Our objective was to develop and validate an Adolescent Asthma Self-Efficacy Questionnaire (AASEQ).The first stage of the study included a review of the literature, interviews with adolescents with asthma and consultations with parents and relevant healthcare professionals to develop a prototype scale. To assess reliability and validity, a further group of adolescents completed the prototype scale, the General Self-Efficacy Scale and KidCOPE (measures coping styles). Retesting was undertaken to assess longitudinal validity.Interviews with 28 adolescents and consultations with other stakeholders resulted in a 38-item prototype scale. Key themes were medication, symptom management, triggers, knowledge, attitude and beliefs around asthma, supportive relationships, schools and healthcare professionals. The prototype scale was completed by 243 adolescents. Factor and reliability analysis reduced it to a 27-item scale with four subsections: symptom management; medication; friends, family and school; and asthma beliefs. The 27-item scale had respectable to excellent internal consistency (α's 0.78-0.91) with results that were stable over time (intra-class correlation=0.82) in 63 subjects who completed it twice. Better adolescent asthma self-efficacy was associated with better general self-efficacy and indices of better asthma management.The AASEQ is a reliable and valid tool that is likely to aid future research and practice focused on adolescent asthma self-management and could be a useful intermediate outcome measure to assess the impact of behavioural interventions.


Attentional cues affect accuracy and reaction time via different cognitive and neural processes.
We investigated whether symbolic endogenous attentional cues affect perceptual accuracy and reaction time (RT) via different cognitive and neural processes. We recorded magnetoencephalography in 19 humans while they performed a cued somatosensory discrimination task in which the cue-target interval was varied between 0 and 1000 ms. Comparing behavioral and neural measures, we show that (1) attentional cueing affects accuracy and RT with different time courses and (2) the time course of our neural measure (anticipatory suppression of neuronal oscillations in stimulus-receiving sensory cortex) only accounts for the accuracy time course. A model is proposed in which the effect on accuracy is explained by a single process (preparatory excitability increase in sensory cortex), whereas the effect on RT is explained by an additional process that is sensitive to cue-target compatibility (post-target comparison between expected and actual stimulus location). These data provide new insights into the mechanisms underlying behavioral consequences of attentional cueing.


A three-dimensional engineered artery model for in vitro atherosclerosis research.
The pathogenesis of atherosclerosis involves dysfunctions of vascular endothelial cells and smooth muscle cells as well as blood borne inflammatory cells such as monocyte-derived macrophages. In vitro experiments towards a better understanding of these dysfunctions are typically performed in two-dimensional cell culture systems. However, these models lack both the three-dimensional structure and the physiological pulsatile flow conditions of native arteries. We here describe the development and initial characterization of a tissue engineered artery equivalent, which is composed of human primary endothelial and smooth muscle cells and is exposed to flow in vitro. Histological analyses showed formation of a dense tissue composed of a tight monolayer of endothelial cells supported by a basement membrane and multiple smooth muscle cell layers. Both low (LDL) and high density lipoproteins (HDL) perfused through the artery equivalent were recovered both within endothelial cells and in the sub-endothelial intima. After activation of the endothelium with either tumour necrosis factor alpha (TNFα) or LDL, monocytes circulated through the model were found to adhere to the activated endothelium and to transmigrate into the intima. In conclusion, the described tissue engineered human artery equivalent model represents a significant step towards a relevant in vitro platform for the systematic assessment of pathogenic processes in atherosclerosis independently of any systemic factors.


Prescription habits for preventative medications among pediatric emergency department physicians at an inner-city teaching hospital.
As asthma presentation is episodic, patients with acute exacerbations often present in the emergency department (ED) where preventative regimen may not always be addressed. Addressing initiation and modification of controller medications in the setting of an acute exacerbation may facilitate improved asthma control and decrease the frequency of ED visits, particularly so for families who receive most of their asthma management in the ED. However, this aspect has not yet been explored. We reviewed a random sample of 363 charts, 10% of the total number of asthmatic children, aged 2-18, seen from January to December 2007 in the pediatric ED of an urban teaching hospital located in Bronx, NY, USA. We quantified the frequency of modification of the preventative regimen and the influence of seasons on this practice. Of these 363 children, 42.4% of patients were not previously on a controller medication. Of these, 9.7% were started on a new controller medication, with a significantly higher percent occurring in the summer months. Of those that were previously on a controller medication, 2.87% were started on a new controller medication and 0.95% had their controller medication dose increased. However, the regimen was not adjusted in 14.3% that had been seen four or more times in the preceding 2 years. Of the total 363 children, 78.5% were discharged from the ED on a short course of oral steroids, and this was not part of their preventative regimen. Only four charts had physician-documented asthma severity classification. We found that the preventative regimen was modified in only 0.9-2% of all asthmatic children seen in an urban ED whereas 78.5% were started on systemic steroids. Asthma severity was evaluated in a very small number of patients. Because modification of preventative regimen requires appropriate asthma severity classification, the inclusion of asthma severity classification as part of routine ED evaluation may encourage physicians to address controller medications in persistent asthmatics.


Heritability of serum TSH, free T4 and free T3 concentrations: a study of a large UK twin cohort.
Thyroid hormone action influences many metabolic and synthetic processes, but the degree of regulation attributed to genes and environmental factors affecting normal variation remains controversial. We investigated the magnitude of the genetic and environmental determination of serum concentrations of free (f) T3, fT4, TSH and the fT4 x TSH product and their variation, in a large cohort of twin pairs. Female dizygous and monozygous twins (849 and 213 pairs, respectively) from the TwinsUK registry (mean age 45.5, range 18-80 years) were studied. Comparison of thyroid parameters within various groups showed no differences between smoking categories, and higher serum TSH and lower fT3 in subjects with positive thyroid antibodies. Using structural equation modelling, we estimated the heritable contribution to serum thyroid parameters (with 95% confidence intervals) to be 65% (58%-71%) for TSH, 65% (58%-71%) for the fT4 x TSH product, 39% (20%-55%) for fT4 and 23% (3%-41%) for fT3. We conclude that genetic regulation is a particularly important determinant of TSH and the fT4 x TSH product, and is a less important determinant of fT4 and fT3 concentrations in Caucasian women. These data from a large well-characterized cohort suggest that while there is a strong heritable contribution to serum TSH, variation in fT4 and fT3 concentrations may be less explained by genetic factors and more driven by environmental effects than previously thought.


Access to Complex Abortion Care Service and Planning Improved through a Toll-Free Telephone Resource Line.
Background. Providing equitable access to the full range of reproductive health services over wide geographic areas presents significant challenges to any health system. We present a review of a service provision model which has provided improved access to abortion care; support for complex issues experienced by women seeking nonjudgmental family planning health services; and a mechanism to collect information on access barriers. The toll-free pregnancy options service (POS) of British Columbia Women's Hospital and Health Centre sought to improve access to services and overcome barriers experienced by women seeking abortion. Methods. We describe the development and implementation of a province-wide toll-free telephone counseling and access facilitation service, including establishment of a provincial network of local abortion service providers in the Canadian province of British Columbia from 1998 to 2010. Results. Over 2000 women annually access service via the POS line, networks of care providers are established and linked to central support, and central program planners receive timely information on new service gaps and access barriers. Conclusion. This novel service has been successful in addressing inequities and access barriers identified as priorities before service establishment. The service provided unanticipated benefits to health care planning and monitoring of provincial health care related service delivery and gaps. This model for low cost health service delivery may realize similar benefits when applied to other health care systems where access and referral barriers exist.


Flow across the canine ileocolonic junction: role of the ileocolonic sphincter.
The role of the canine ileocolonic sphincter (ICS) in influencing transit of fluids and absorption of water in the ileum was assessed in loops with or without the ICS. Two sets of four dogs each were equipped with isolated ileal loops 40 cm long, attached to the intact bowel through a neuromuscular bridge. In one set, the loop included the ICS and it terminated in an end colostomy; in the other, the loop ended immediately proximal to the ICS, as an ileostomy. Electrical and mechanical signals were recorded from serosal electrodes and strain gauges, respectively, during perfusion of loops with an isotonic solution at rates from 0.7 to 10.0 ml/min. Loops without an ICS propelled fluid by steady, continuous flow at all rates of perfusion; loops with the ICS in place moved fluids in this way only at 10 ml/min. At greater rates of perfusion, fasting cycles of motility were inhibited in all loops and a random pattern of motility developed; this presumably facilitated more steady flow of fluids. At the slowest rate of perfusion, transit times were longer when the ICS was present, but at faster rates both loops showed similar transit times. Presence of the ICS was associated with increased volumes of fluid in the loop and increased absorption of water, especially when loops were perfused slowly. The canine ICS influences flow of saline and absorption in the terminal ileum, but only when flow rates are low.


Lymphotoxin alpha beta 2 (membrane lymphotoxin) is critically important for resistance to Leishmania major infection in mice.
Although the essential role of TNF-alpha in the control of intracellular pathogens including Leishmania major is well established, it is uncertain whether the related cytokine lymphotoxin alphabeta2 (LTalpha1beta2, membrane lymphotoxin) plays any role in this process. In this study, we investigated the contribution of membrane lymphotoxin in host response to L. major infection by using LTbeta-deficient (LTbeta(-/-)) mice on the resistant C57BL/6 background. Despite mounting early immune responses comparable to those of wild-type (WT) mice, LTbeta(-/-) mice developed chronic nonhealing cutaneous lesions due to progressive and unresolving inflammation that is accompanied by uncontrolled parasite proliferation. This chronic disease was associated with striking reduction in IL-12 and Ag-specific IFN-gamma production by splenocytes from infected mice. Consistent with defective cellular immune response, infected LTbeta(-/-) mice had significantly low Ag-specific serum IgG1 and IgG2a levels compared with WT mice. Although administration of rIL-12 to L. major-infected LTbeta(-/-) mice caused complete resolution of chronic lesions, it only partially (but significantly) reduced parasite proliferation. In contrast, blockade of LIGHT signaling in infected LTbeta(-/-) mice resulted in acute and progressive lesion development, massive parasite proliferation, and dissemination to the visceral organs. Although infected LTbeta(-/-) WT bone marrow chimeric mice were more resistant than LTbeta(-/-) mice, they still had reduced ability to control parasites and showed defective IL-12 and IFN-gamma production compared with infected WT mice. These results suggest that membrane lymphotoxin plays critical role in resistance to L. major by promoting effective T cell-mediated anti-Leishmania immunity.


Enhancement of fine detail in the presence of large radiance differences.
A technique is described for enhancing fine detail in the production of radiance pictures of targets in which large differences also occur, and where the dynamic range of the picture viewing system is limited. This is achieved by scannig a raster with a mirror-chopper fed detector over the target area, and referencing one sampled area on this target against the next, the radiance intensity from which is reduced by a constant factor. The detector output is then a difference curve related to a derivative trace of the radiance profile, superimposed on the true radiance profile reduced in intensity. The method is compared with a similar technique previously used by Low(2), and examples of the use of the present technique both in the laboratory and in observing a feature on the lunar surface are included.


The Utility of Early Warning Score in Adults Presenting With Sepsis in the Emergency Department of a Low Resource Setting.
Background Sepsis is a condition with high mortality and morbidity. Delay in early recognition and prompt management results in higher mortality. There are many clinical scores to identify early sepsis; however, Early Warning Score (EWS) has clinical/physiological parameters that are easy to apply in the ED for timely diagnosis and management. In the present study, we collected information regarding the utilization of EWS in timely identifying the sick patients at triage of a tertiary care center. Methods This study was a descriptive cross-sectional investigation conducted in the ED of Aga Khan University Hospital in Karachi, the largest metropolitan city in Pakistan. A total of 240 participants were selected by non-probability convenient sampling after fulfilling the inclusion criteria. Data collected included EWS criteria, demography, length of hospital stay, patient disposition (ward, intensive care or high dependency area), and differentials like sepsis, severe sepsis or septic shock. Results A total of 240 patients were enrolled, out of which 139 (57.9%) patients were male, and 101 (42.1%) were female with a mean age of 52.7 ± 15.3 years (range: 18 to 80 years). In this study, the length of stay (LOS) was 2.2 ± 1.1 (range: one to six days), and there was an EWS of 8.2 ± 2.6 (4-15). There were 143 patients in the elderly age group > 50 years (59.6%); however, most elderly presented with sepsis among both age groups. The least affected age group was aged 16 to 30 years, with 23 (9.6%) cases. An EWS >7 is best to detect cases with sepsis or severe sepsis with a sensitivity of 98.5% (95% CI: 92.13 to 99.92) and specificity of 89.57% (95% CI: 82.64 to 93.93). Similarly, the EWS for severe sepsis or septic shock was >9 with a sensitivity of 86.76% (95% CI: 76.72 to 92.88) and specificity of 88.24% (95% CI: 78.47 to 93.92). Conclusions This study revealed that the sensitivity and specificity of EWS for the detection of sepsis, severe sepsis and septic shock was found to be high; hence, it could be a valuable and readily useable system for early diagnosis and proper management of sepsis, severe sepsis, and septic shock.


An investigation of patients' motivations for their participation in genetics-related research.
Qualitative interview study. Fifty-nine patients with a family history of cancer who attend a regional cancer genetics clinic in the UK were interviewed about their current and previous research experiences. Interviewees gave a range of explanations for research participation. These were categorised as (a) social--research participation benefits the wider society by progressing science and improving treatment for everyone; (b) familial--research participation may improve healthcare and benefit current or future generations of the participant's family; and (c) personal--research participation provides therapeutic or non-therapeutic benefits for oneself. We discuss the distinction drawn between motives for research participation focused upon self (personal) and others (familial/social), and observe that personal, social and familial motives can be seen as interdependent. For example, research participation that is undertaken to benefit others, particularly relatives, may also offer a number of personal benefits for self, such as enabling participants to feel that they have discharged their social or familial obligations. We argue for the need to move away from simple, static, individualised notions of research participation to a more complex, dynamic and inherently social account.


Direct measurement of the total decay width of the top quark.
We present a measurement of the total decay width of the top quark using events with top-antitop quark pair candidates reconstructed in the final state with one charged lepton and four or more hadronic jets. We use the full Tevatron run II data set of sqrt[s]=1.96 TeV proton-antiproton collisions recorded by the CDF II detector. The top quark mass and the mass of the hadronically decaying W boson are reconstructed for each event and compared with distributions derived from simulated signal and background samples to extract the top quark width (Γtop) and the energy scale of the calorimeter jets with in situ calibration. For a top quark mass Mtop=172.5 GeV/c2, we find 1.10<Γtop<4.05 GeV at 68% confidence level, which is in agreement with the standard model expectation of 1.3 GeV and is the most precise direct measurement of the top quark width to date.


Future career plans of a cohort of senior doctors working in the National Health Service.
To report on the future career plans of senior doctors working in the NHS. Postal questionnaires. All doctors who qualified in 1977 from all UK medical schools. Future plans and whether participants had any unmet needs for advice on how to put their future plans into effect. 25% definitely intended to continue with their current employment on the same basis until they retired; 75% hoped for change. A reduction in working hours was the most commonly desired change; but a substantial percentage also wanted changes in job content. 50% of respondents intended definitely (17%) or probably (33%) to work in the NHS to their normal retirement age; and 37% definitely (20%) or probably (17%) intended to retire early. 48% had made plans, in addition to the standard pension, to facilitate early retirement. The main factors given for considering early retirement were family reasons and wanting more time for leisure, a desire to maintain good health, excessive pressure of work, and disillusionment with NHS changes. A reduction in workload would be the greatest inducement to stay. 31% of respondents reported that they had unmet needs for advice about their future plans. Of these, about half were needs for advice about planning for retirement. Many senior NHS doctors would like to reduce their working hours. Less than a quarter definitely intend to work in the NHS to normal retirement age. Even for senior doctors, advice on career development is needed.


Evolutionary origins and functions of the carotenoid biosynthetic pathway in marine diatoms.
Carotenoids are produced by all photosynthetic organisms, where they play essential roles in light harvesting and photoprotection. The carotenoid biosynthetic pathway of diatoms is largely unstudied, but is of particular interest because these organisms have a very different evolutionary history with respect to the Plantae and are thought to be derived from an ancient secondary endosymbiosis between heterotrophic and autotrophic eukaryotes. Furthermore, diatoms have an additional xanthophyll-based cycle for dissipating excess light energy with respect to green algae and higher plants. To explore the origins and functions of the carotenoid pathway in diatoms we searched for genes encoding pathway components in the recently completed genome sequences of two marine diatoms. Consistent with the supplemental xanthophyll cycle in diatoms, we found more copies of the genes encoding violaxanthin de-epoxidase (VDE) and zeaxanthin epoxidase (ZEP) enzymes compared with other photosynthetic eukaryotes. However, the similarity of these enzymes with those of higher plants indicates that they had very probably diversified before the secondary endosymbiosis had occurred, implying that VDE and ZEP represent early eukaryotic innovations in the Plantae. Consequently, the diatom chromist lineage likely obtained all paralogues of ZEP and VDE genes during the process of secondary endosymbiosis by gene transfer from the nucleus of the algal endosymbiont to the host nucleus. Furthermore, the presence of a ZEP gene in Tetrahymena thermophila provides the first evidence for a secondary plastid gene encoded in a heterotrophic ciliate, providing support for the chromalveolate hypothesis. Protein domain structures and expression analyses in the pennate diatom Phaeodactylum tricornutum indicate diverse roles for the different ZEP and VDE isoforms and demonstrate that they are differentially regulated by light. These studies therefore reveal the ancient origins of several components of the carotenoid biosynthesis pathway in photosynthetic eukaryotes and provide information about how they have diversified and acquired new functions in the diatoms.


Albuminuria and renal insufficiency prevalence guides population screening: results from the NHANES III.
A number of screening criteria, applied either at a single point in time or serially, can be used for the purpose of identifying individuals at risk of end-stage renal disease (ESRD). This study focused on two such criteria measured on a single occasion, proteinuria and renal insufficiency, and examined their prevalence in a sample representative of the adult U.S. non-institutionalized population. Such knowledge guides the utility of population screening to prevent ESRD. The prevalence of albuminuria (microalbuminuria and macroalbuminuria from a random urine albumin-to-creatinine ratio) and renal insufficiency [glomerular filtration rate (GFR) estimated from serum creatinine] was determined in different age categories in various adult screening groups in the cross-sectional Third National Health and Nutrition Examination Survey (NHANES III). A total of 14,622 adult participants were included in the analysis. In the general population, 8.3% and 1.0% of participants demonstrated microalbuminuria and macroalbuminuria, respectively. To identify one case of albuminuria, one would need to screen three persons with diabetes mellitus, seven non-diabetic hypertensive persons, or six persons over the age of 60. When albuminuria and renal insufficiency were considered together, it was clear that these tests were identifying different segments of the population; 37% of participants with a GFR less than 30 mL/min/1.73 m2 demonstrated no albuminuria. Non-albuminuric renal insufficiency was most evident in the ages of 60 to 79; 34% of diabetics, and 63% of non-diabetic hypertensives with a GFR less than 30 mL/min/1.73 m2 demonstrated no albuminuria. Albuminuria is prevalent, and when considered together, screening tests of albuminuria and renal insufficiency measured on a single occasion identify different segments of the population. The prevalence of albuminuria and renal insufficiency in populations of interest should be considered, as this knowledge has implications for the effectiveness of screening.


Emergency Department MRI Scanning of Patients with Multiple Sclerosis: Worthwhile or Wasteful?
The increasing use of the emergency department MR imaging scanner at our institution raises questions about its added value to certain patient groups. We hypothesized that the use of emergency department MR imaging for identifying active demyelination in MS patients presenting with new neurologic symptoms would be of low yield. Electronic medical records were reviewed for patients with MS who had emergency department MR imaging scans for a suspected MS exacerbation between March 1, 2014, and March 1, 2016. Details surrounding patient disposition, imaging, diagnosis, and management were determined. Of 115 patients in our study, 48 (41.7%) were ultimately diagnosed with an MS exacerbation. Nearly all patients with MS exacerbations (87.5%, 42/48) had active demyelination on their emergency department MR imaging, identified on 30.6% (33/108) of brain MRIs and 20.4% (19/93) of spinal MRIs. The presence of active demyelination at MRI was significantly associated with the ultimate diagnosis of an MS exacerbation (P < .001). MR imaging activity isolated to the spinal cord (ie, not found on concurrent brain MR imaging) was present in only 9 of 93 (9.7%) cases. Pseudoexacerbations accounted for 18 of the alternative diagnoses. Emergency department MR imaging is a worthwhile endeavor from a diagnostic standpoint for MS exacerbations despite not being part of the diagnostic criteria. This finding has corresponding downstream impact on management decisions to admit and/or administer intravenous steroids. However, we raise the question of whether clinicians over-rely on emergency department imaging for making exacerbation diagnoses. Additionally, spinal MR imaging is of questionable value as an addition to brain MR imaging due to a low yield of isolated spinal disease.


Associations of proanthocyanidin intake with renal function and clinical outcomes in elderly women.
Progression to chronic renal failure involves accelerated atherosclerosis and vascular calcification. Oxidative stress and endothelial dysfunction play a role in renal failure pathophysiology. In addition to improving vascular health and function, proanthocyanidins have been shown to exert renoprotective effects in animal models. Thus we hypothesize that proanthocyanidins may contribute to the maintenance of healthy renal function. Determine the association of habitual proanthocyanidin intake with renal function and the risk of clinical renal outcomes in a population of elderly women. 948 women aged over 75 y, free of prevalent renal disease at baseline, were randomly selected from ambulant Caucasian women. Proanthocyanidin consumption was determined using a validated food frequency questionnaire and the United States Department of Agriculture proanthocyanidin food content database. Fasting serum cystatin C and creatinine were assessed at baseline. Renal failure hospitalisations and deaths were assessed over 5 years of follow-up through the Western Australia Data Linkage System. Compared to participants with low consumption, participants in the highest tertile of proanthocyanidin intake had a 9% lower cystatin C concentration (P<0.001). High proanthocyanidin consumers were at 50% lower risk of moderate chronic kidney insufficiency, and 65% lower risk of experiencing a 5-year renal disease event (P<0.05). These relationships remained significant following adjustment for renal disease risk factors and diet-related potential confounders. Increased consumption of proanthocyanidins was associated with better renal function and substantially reduced renal associated events, which has been supported by mechanistic and animal model data. Proanthocyanidin intake should be further examined as a dietary contributor to better renal health.


Energy-Renormalization for Achieving Temperature Transferable Coarse-Graining of Polymer Dynamics.
The bottom-up prediction of the properties of polymeric materials based on molecular dynamics simulation is a major challenge in soft matter physics. Coarse-grained (CG) models are often employed to access greater spatiotemporal scales required for many applications, but these models normally experience significantly altered thermodynamics and highly accelerated dynamics due to the reduced number of degrees of freedom upon coarse-graining. While CG models can be calibrated to meet certain properties at particular state points, there is unfortunately no temperature transferable and chemically specific coarse-graining method that allows for modeling of polymer dynamics over a wide temperature range. Here, we pragmatically address this problem by "correcting" for deviations in activation free energies that occur upon coarse-graining the dynamics of a model polymeric material (polystyrene). In particular, we propose a new strategy based on concepts drawn from the Adam-Gibbs (AG) theory of glass formation. Namely we renormalize the cohesive interaction strength and effective interaction length-scale parameters to modify the activation free energy. We show that this energy-renormalization method for CG modeling allows accurate prediction of atomistic dynamics over the Arrhenius regime, the non-Arrhenius regime of glass formation, and even the non-equilibrium glassy regime, thus allowing for the predictive modeling of dynamic properties of polymer over the entire range of glass formation. Our work provides a practical scheme for establishing temperature transferable coarse-grained models for predicting and designing the properties of polymeric materials.


Forensic telepsychiatry: a possible solution for South Africa?
South Africa has a shortage of facilities and psychiatrists to assess adjudicative competence of prisoners awaiting assessment under sections 77 to 79 of the Criminal Procedures Act of 1977. Various solutions have been proposed by the Department of Health. The recent linking of a Magistrate's court and a prison by videoconferencing offers the opportunity to implement a forensic telepsychiatry service. The literature on forensic telepsychiatry for assessment of adjudicative competence was reviewed. The electronic databases, PubMed, Scopus, Cinahl and Google Scholar were searched for papers on forensic telepsychiatry. The inclusion criterion was papers reporting the use of videoconferencing for assessment of adjudicative competence or for assessment for referral out of the judicial system, by psychiatrists or psychologists. 411 papers were found of which 13, published between 1997 and 2008 were relevant. The use of videoconferencing for forensic psychiatric assessment was reported from four countries. The courts in those jurisdictions have accepted the use of videoconferencing for assessment and no successful appeals have been mounted on the basis of the use of videoconferencing for assessment. User satisfaction has not been reported for assessing adjudicative competence. Forensic telepsychiatry has been found to be cost effective, improve access to scarce specialist skills and reduce transport of prisoners under guard to hospitals or psychiatrists to prisons. There is nothing in the literature to suggest that a forensic telepsychiatry service is not feasible in South Africa and a pilot project is being planned.


West Nile virus positive blood donation and subsequent entomological investigation, Austria, 2014.
The detection of West Nile virus (WNV) nucleic acid in a blood donation from Vienna, Austria, as well as in Culex pipiens pupae and egg rafts, sampled close to the donor's residence, is reported. Complete genomic sequences of the human- and mosquito-derived viruses were established, genetically compared and phylogenetically analyzed. The viruses were not identical, but closely related to each other and to recent Czech and Italian isolates, indicating co-circulation of related WNV strains within a confined geographic area. The detection of WNV in a blood donation originating from an area with low WNV prevalence in humans (only three serologically diagnosed cases between 2008 and 2014) is surprising and emphasizes the importance of WNV nucleic acid testing of blood donations even in such areas, along with active mosquito surveillance programs.


Sparse representation for coarse and fine object recognition.
This paper offers a sparse, multiscale representation of objects. It captures the object appearance by selection from a very large dictionary of Gaussian differential basis functions. The learning procedure results from the matching pursuit algorithm, while the recognition is based on polynomial approximation to the bases, turning image matching into a problem of polynomial evaluation. The method is suited for coarse recognition between objects and, by adding more bases, also for fine recognition of the object pose. The advantages over the common representation using PCA include storing sampled points for recognition is not required, adding new objects to an existing data set is trivial because retraining other object models is not needed, and significantly in the important case where one has to scan an image over multiple locations in search for an object, the new representation is readily available as opposed to PCA projection at each location. The experimental result on the COIL-100 data set demonstrates high recognition accuracy with real-time performance.


Role of Ca2+ and myosin light chain phosphorylation in regulation of smooth muscle.
The time course of phosphorylation of the 20,000-dalton myosin light chain (LC 20) was determined during contraction and relaxation in K+- and histamine-stimulated medial strips of swine carotid arteries. Resting LC 20 phosphorylation levels of 0.15 mol P/mol LC 20 rapidly increased to peak values of 0.6-0.7 mol P/mol LC 20 after stimulation and then declined significantly, although stress continued to rise to a stable steady-state maximum. LC 20 dephosphorylation after agonist washout preceded the decline in isometric stress. Over the entire contraction-relaxation cycle, phosphorylation was correlated with shortening velocity and not with developed stress. The maximum shortening velocity with no external load (Vo) was directly proportional to LC 20 phosphorylation (r = 0.986). The data indicate that LC 20 phosphorylation is necessary for cross-bridge cycling leading to shortening or stress development but that stress can be maintained by additional mechanisms. We suggest that dephosphorylation of an attached cross bridge in the presence of Ca2+ arrests the cycle, forming an attached, noncycling cross bridge.


Spontaneous abortion and exposure to electric blankets and heated water beds.
We conducted a prospective study (N = 2,967) to evaluate the relation of spontaneous abortion with use of electrically heated beds (electric blankets and heated water beds) during pregnancy. At interview, 61.5% of women were at less than 12 weeks gestation, and 38.5% were between 13 and 16 weeks; thus, very early pregnancy losses would have been excluded. Information regarding exposure to electric beds was obtained for the month of conception and the 7 days before interview. Electric blanket use at conception was associated with an increased risk of spontaneous abortion in the unadjusted analysis [relative risk (RR) = 1.84; 95% confidence interval (CI) = 1.08-3.13], but adjustment for other factors reduced the risk slightly [odds ratio (OR) = 1.74; 95% CI = 0.96-3.15]. Heated water bed use was not associated with an increased risk of spontaneous abortion at conception (OR = 0.59; 95% CI = 0.33-1.07) or at interview (OR = 0.63; 95% CI = 0.36-1.12). Measures of dose response (daily use, hours of use, or temperature setting) were not associated with increased risk. Wire code data were obtained for the first, or only, house lived in during pregnancy. Women living in homes classified as "very high" or "ordinary high" current configuration were not at greater risk than women living in homes with buried wires. Nor was there any trend for increased risk of spontaneous abortion by wire code category. This study does not support the hypothesis that use of electric beds or residence in a high current configuration home increases the risk of spontaneous abortion; however, it indicates that electric blanket use at the time of conception and in early pregnancy may be associated with a slight increase in risk of pregnancy loss.


In vivo three-dimensional confocal laser scanning microscopy of corneal surface and epithelium.
To evaluate in vivo three-dimensional (3-D) confocal laser scanning microscopy (CLSM) as a technique for visualising the corneal surface and epithelium. Ten human corneas (three from healthy volunteers, three with bullous keratopathy, three from patients following penetrating keratoplasty, and one with corneal erosion) were examined by 3-D CLSM. A novel polymethyl methacrylate (PMMA) contact cap was designed to minimise artefacts due to applanation pressure. 3-D reconstruction and different visualisation techniques (volume rendering, cross-section, en face view, oblique section and surface reconstruction) were performed to demonstrate alterations to corneal surface and epithelium. Image quality (cell identification, motion blur, absence of compression artefacts, imaging of superficial structures and of subepithelial nerve plexus) was considerably superior to that obtained using a conventional contact cap with a planar surface. 3-D CLSM permits in vivo visualisation and analysis of the corneal surface and of spatial arrangement at the cellular level in epithelium in normal and pathological corneas. The novel design of the contact cap minimises artefacts due to applanation pressure and improves the image quality of epithelial structures. The method provides a basis for further in vivo studies of alterations to corneal surface structure and its cellular arrangement.


Chiral templating of self-assembling nanostructures by circularly polarized light.
The high optical and chemical activity of nanoparticles (NPs) signifies the possibility of converting the spin angular momenta of photons into structural changes in matter. Here, we demonstrate that illumination of dispersions of racemic CdTe NPs with right- (left-)handed circularly polarized light (CPL) induces the formation of right- (left-)handed twisted nanoribbons with an enantiomeric excess exceeding 30%, which is ∼10 times higher than that of typical CPL-induced reactions. Linearly polarized light or dark conditions led instead to straight nanoribbons. CPL 'templating' of NP assemblies is based on the enantio-selective photoactivation of chiral NPs and clusters, followed by their photooxidation and self-assembly into nanoribbons with specific helicity as a result of chirality-sensitive interactions between the NPs. The ability of NPs to retain the polarization information of incident photons should open pathways for the synthesis of chiral photonic materials and allow a better understanding of the origins of biomolecular homochirality.


Homeobox genes and pattern formation in the vertebrate limb.
The developing vertebrate limb is a powerful system to study genes potentially involved in pattern formation. Many such candidate genes encode transcription factors belonging to the class of the "homeodomain" proteins. In this short review, we discuss the possible functions of different subfamilies of homeobox genes. Genes belonging to the Hox family (related to the Drosophila homoeotic genes), such as the HOX-1, HOX-3, and HOX-4, complexes are probably among those encoding the patterning information. Their differential expression in the mesenchymal compartment is proposed to be responsible for the determination of the various axial elements. Other homeobox-containing genes are expressed in both the mesenchyme of the progress zone and the ectodermal ridge. These genes, Hox-7.1 and Hox-8.1, are related to the Drosophila msh gene and could be involved in epithelial-mesenchymal interactions linking the growth of the system to its patterning.


Prediction of hydrogen flux through sulfur-tolerant binary alloy membranes.
Metal membranes play a vital role in hydrogen purification. Defect-free membranes can exhibit effectively infinite selectivity but must also provide high fluxes, resistance to poisoning, long operational lifetimes, and low cost. Alloying offers one route to improve on membranes based on pure metals such as palladium. We show how ab initio calculations and coarse-grained modeling can accurately predict hydrogen fluxes through binary alloy membranes as functions of alloy composition, temperature, and pressure. Our approach, which requires no experimental input apart from knowledge of bulk crystal structures, is demonstrated for palladium-copper alloys, which show nontrivial behavior due to the existence of face-centered cubic and body-centered cubic crystal structures and have the potential to resist sulfur poisoning. The accuracy of our approach is examined by a comparison with extensive experiments using thick foils at elevated temperatures. Our experiments also demonstrate the ability of these membranes to resist poisoning by hydrogen sulfide.


Proposed mechanisms in renal tubular crystal retention.
The production of concentrated urine inevitably leads to the precipitation of poorly soluble waste salts in the renal tubular fluid. These crystallization processes are physiologic and without consequences as long as all crystals are excreted with the urine. The retention of crystals in the renal tubules, however, may lead to tubular nephrocalcinosis. Here, we present a brief survey of the possible mechanisms involved in this process, which seems to depend predominantly on the presence of regenerating/(re)differentiating cells in the renal tubules. Crystal binding to the surface of these cells can be mediated by a number of luminal membrane molecules, including acidic fragment of nucleolin-related protein, annexin-II, osteopontin, and hyaluronan.


In situ vocal fold properties and pitch prediction by dynamic actuation of the songbird syrinx.
The biomechanics of sound production forms an integral part of the neuromechanical control loop of avian vocal motor control. However, we critically lack quantification of basic biomechanical parameters describing the vocal organ, the syrinx, such as material properties of syringeal elements, forces and torques exerted on, and motion of the syringeal skeleton during song. Here, we present a novel marker-based 3D stereoscopic imaging technique to reconstruct 3D motion of servo-controlled actuation of syringeal muscle insertions sites in vitro and focus on two muscles controlling sound pitch. We furthermore combine kinematic analysis with force measurements to quantify elastic properties of sound producing medial labia (ML). The elastic modulus of the zebra finch ML is 18 kPa at 5% strain, which is comparable to elastic moduli of mammalian vocal folds. Additionally ML lengthening due to musculus syringealis ventralis (VS) shortening is intrinsically constraint at maximally 12% strain. Using these values we predict sound pitch to range from 350-800 Hz by VS modulation, corresponding well to previous observations. The presented methodology allows for quantification of syringeal skeleton motion and forces, acoustic effects of muscle recruitment, and calibration of computational birdsong models, enabling experimental access to the entire neuromechanical control loop of vocal motor control.


Benefits of mobile reporting systems in social home care: the case of seven Swedish municipalities.
Mobile systems are widely adopted in healthcare services. Mobile reporting systems have been recently introduced for social home care by municipalities in Sweden. The study aims to assess the benefits of using these systems. We followed an expert survey approach. Data were collected by means of telephone interviews with the experts in charge of managing and implementing the systems at the municipalities. In addition, several workshops were organized for assessing the economic value of the systems at one municipality. We performed thematic analysis and cost-benefit analysis of the data. The thematic analysis showed the three main benefits of using the mobile reporting systems in social home care: municipal benefits, care providers' benefits, and care recipients' benefits. The cost-benefit analysis indicated that the systems could bring substantial long-term economic value for municipalities. The results also revealed the difficulties encountered at the early stage of the deployment and implementation of the systems. The mobile systems yield benefits for all the actors, that is, municipalities, care recipients and care providers. These enhance the public-private coordination and cooperation in social home care in Sweden. The municipalities are called upon to address change management and technical challenges in the implementation.


Measuring long-lived 13C2 state lifetimes at natural abundance.
Long-lived disconnected eigenstates (for example, the singlet state in a system with two nearly equivalent carbons, or the singlet-singlet state in a system with two chemically equivalent carbons and two chemically equivalent hydrogens) hold the potential to drastically extend the lifetime of hyperpolarization in molecular tracers for in vivo magnetic resonance imaging (MRI). However, a first-principles calculation of the expected lifetime (and thus selection of potential imaging agents) is made very difficult because of the large variety of relevant intra- and intermolecular relaxation mechanisms. As a result, all previous measurements relied on costly and time consuming syntheses of (13)C labeled compounds. Here we show that it is possible to determine (13)C singlet state lifetimes by detecting the naturally abundant doubly-labeled species. This approach allows for rapid and low cost screening of potential molecular biomarkers bearing long-lived states.


Circulating fibrocytes stabilize blood vessels during angiogenesis in a paracrine manner.
Accumulating evidence supports that circulating fibrocytes play important roles in angiogenesis. However, the specific role of fibrocytes in angiogenesis and the underlying mechanisms remain unclear. In this study, we found that fibrocytes stabilized newly formed blood vessels in a mouse wound-healing model by inhibiting angiogenesis during the proliferative phase and inhibiting blood vessel regression during the remodeling phase. Fibrocytes also inhibited angiogenesis in a Matrigel mouse model. In vitro study showed that fibrocytes inhibited both the apoptosis and proliferation of vascular endothelial cells (VECs) in a permeable support (Transwell) co-culture system. In a three-dimensional collagen gel, fibrocytes stabilized the VEC tubes by decreasing VEC tube density on stimulation with growth factors and preventing VEC tube regression on withdrawal of growth factors. Further mechanistic investigation revealed that fibrocytes expressed many prosurvival factors that are responsible for the prosurvival effect of fibrocytes on VECs and blood vessels. Fibrocytes also expressed angiogenesis inhibitors, including thrombospondin-1 (THBS1). THBS1 knockdown partially blocked the fibrocyte-induced inhibition of VEC proliferation in the Transwell co-culture system and recovered the fibrocyte-induced decrease of VEC tube density in collagen gel. Purified fibrocytes transfected with THBS1 siRNA partially recovered the fibrocyte-induced inhibition of angiogenesis in both the wound-healing and Matrigel models. In conclusion, our findings reveal that fibrocytes stabilize blood vessels via prosurvival factors and anti-angiogenic factors, including THBS1.


Methazolamide Attenuates the Development of Diabetic Cardiomyopathy by Promoting β-Catenin Degradation in Type 1 Diabetic Mice.
Methazolamide (MTZ), a carbonic anhydrase inhibitor, has been shown to inhibit cardiomyocyte hypertrophy and exert a hypoglycemic effect in patients with type 2 diabetes and diabetic db/db mice. However, whether MTZ has a cardioprotective effect in the setting of diabetic cardiomyopathy is not clear. We investigated the effects of MTZ in a mouse model of streptozotocin-induced type 1 diabetes mellitus (T1DM). Diabetic mice received MTZ by intragastric gavage (10, 25, or 50 mg/kg, daily for 16 weeks). In the diabetic group, MTZ significantly reduced both random and fasting blood glucose levels and improved glucose tolerance in a dose-dependent manner. MTZ ameliorated T1DM-induced changes in cardiac morphology and dysfunction. Mechanistic analysis revealed that MTZ blunted T1DM-induced enhanced expression of β-catenin. Similar results were observed in neonatal rat cardiomyocytes (NRCMs) and adult mouse cardiomyocytes treated with high glucose or Wnt3a (a β-catenin activator). There was no significant change in β-catenin mRNA levels in cardiac tissues or NRCMs. MTZ-mediated β-catenin downregulation was recovered by MG132, a proteasome inhibitor. Immunoprecipitation and immunofluorescence analyses showed augmentation of AXIN1-β-catenin interaction by MTZ in T1DM hearts and in NRCMs treated with Wnt3a; thus, MTZ may potentiate AXIN1-β-catenin linkage to increase β-catenin degradation. Overall, MTZ may alleviate cardiac hypertrophy by mediating AXIN1-β-catenin interaction to promote degradation and inhibition of β-catenin activity. These findings may help inform novel therapeutic strategy to prevent heart failure in patients with diabetes.


Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders.
The phytocannabinoid-based medicine Sativex® is currently marketed for the treatment of spasticity and pain in multiple sclerosis patients and is being investigated for other central and peripheral pathological conditions. It may also serve in Veterinary Medicine for the treatment of domestic animals, in particular for dogs affected by different pathologies, including human-like pathological conditions. With the purpose of assessing different dosing paradigms for using Sativex in Veterinary Medicine, we investigated its pharmacokinetics when administered to naïve dogs via sublingual delivery. In the single dose arm of the study, adult Beagle dogs were treated with 3 consecutive sprays of Sativex, and blood samples were collected at 12 intervals up to 24 h later. In the multiple dose arm of the study, Beagle dogs received 3 sprays daily for 14 days, and blood samples were collected for 24 h post final dose. Blood was used to obtain plasma samples and to determine the levels of cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC) and its metabolite 11-hydroxy-Δ9-THC. Maximal plasma concentrations of both Δ9-THC (Cmax = 18.5 ng/mL) and CBD (Cmax = 10.5 ng/mL) were achieved 2 h after administration in the single dose condition and at 1 h in the multiple dose treatment (Δ9-THC: Cmax = 24.5 ng/mL; CBD: Cmax = 15.2 ng/mL). 11hydroxy-Δ9-THC, which is mainly formed in the liver from Δ9-THC, was almost undetected, which is consistent with the use of sublingual delivery. A potential progressive accumulation of both CBD and Δ9-THC was detected following repeated exposure, with maximum plasma concentrations for both cannabinoids being achieved following multiple dose. Neurological status, body temperature, respiratory rate and some hemodynamic parameters were also recorded in both conditions, but in general, no changes were observed. In conclusion, this study demonstrates that single or multiple dose sublingual administration of Sativex to naïve dogs results in the expected pharmacokinetic profile, with maximal levels of phytocannabinoids detected at 1-2 h and suggested progressive accumulation after the multiple dose treatment.


A Bayesian QTL linkage analysis of the common dataset from the 12th QTLMAS workshop.
To compare the power of various QTL mapping methodologies, a dataset was simulated within the framework of 12th QTLMAS workshop. A total of 5865 diploid individuals was simulated, spanning seven generations, with known pedigree. Individuals were genotyped for 6000 SNPs across six chromosomes. We present an illustration of a Bayesian QTL linkage analysis, as implemented in the special purpose software FlexQTL. Most importantly, we treated the number of bi-allelic QTL as a random variable and used Bayes Factors to infer plausible QTL models. We investigated the power of our analysis in relation to the number of phenotyped individuals and SNPs. We report clear posterior evidence for 12 QTL that jointly explained 30% of the phenotypic variance, which was very close to the total of included simulation effects, when using all phenotypes and a set of 600 SNPs. Decreasing the number of phenotyped individuals from 4665 to 1665 and/or the number of SNPs in the analysis from 600 to 120 dramatically reduced the power to identify and locate QTL. Posterior estimates of genome-wide breeding values for a small set of individuals were given. We presented a successful Bayesian linkage analysis of a simulated dataset with a pedigree spanning several generations. Our analysis identified all regions that contained QTL with effects explaining more than one percent of the phenotypic variance. We showed how the results of a Bayesian QTL mapping can be used in genomic prediction.


Cerebral amyloid angiopathy presenting as a brain mass.
The MR images of a patient with cerebral amyloid angiopathy (a localized vascular deposition of amyloid without evidence of systemic amyloidosis) showed an extensive right temporoparietal lobe mass with frontal lobe extension that was slightly hypointense on T1-weighted images and heterogeneously hyperintense on T2-weighted images. No contrast enhancement was identified on MR imaging.


Lamium maculatum is a Natural Host for Cucumber mosaic virus.
Lamium maculatum L. (spotted dead-nettle) is a flowering perennial ornamental that is commonly grown as a landscape plant for an effective ground cover. In June 2010, severe mosaic accompanied by reddish brown necrosis and leaf deformation was noticed on 80% of L. maculatum growing in shade under trees and shrubs in Sarajevo (Bosnia and Herzegovina). Leaves from 10 symptomatic L. maculatum plants were sampled and analyzed by double-antibody sandwich (DAS)-ELISA using commercial diagnostic kits (Bioreba AG, Reinach, Switzerland) against Cucumber mosaic virus (CMV), Tomato spotted wilt virus (TSWV), and Impatiens necrotic spot virus (INSV), the most important viral pathogens of ornamental plants (1,2). Commercial positive and negative controls and extracts from healthy L. maculatum leaves were included in each assay. All samples tested negative for TSWV and INSV and positive for CMV. The virus was mechanically transmitted to test plants and young virus-free plants of L. maculatum using 0.01 M phosphate buffer (pH 7). The virus caused chlorotic local lesions on Chenopodium quinoa, while systemic mosaic was observed on Capsicum annuum 'Rotund,' Nicotiana rustica, N. glutinosa, N. tabacum 'White Burley,' and Phaseolus vulgaris 'Top Crop.' The virus was transmitted mechanically to L. maculatum and induced symptoms resembling those observed on the source plants. Inoculated plants were assayed by DAS-ELISA and all five inoculated plants of each species tested positive for CMV. The presence of CMV in L. maculatum as well as mechanically infected N. glutinosa plants was further confirmed by RT-PCR. Total RNA from symptomatic leaves was isolated using RNeasy Plant Mini Kit (Qiagen, Hilden, Germany) and RT-PCR was performed with the One-Step RT-PCR Kit (Qiagen) following the manufacturer's instructions. The primer pair, CMVAu1u/CMVAu2d, that amplifies the entire coat protein (CP) gene and part of 3'- and 5'-UTRs was used for both amplification and sequencing (4). Total RNA obtained from the Serbian CMV isolate from pumpkin (GenBank Accession No. HM065510) and a healthy L. maculatum plant were used as positive and negative controls, respectively. All naturally and mechanically infected plants as well as the positive control yielded an amplicon of the expected size (850 bp). No amplicon was observed in the healthy control. The amplified product derived from isolate 3-Lam was purified (QIAquick PCR Purification Kit, Qiagen), directly sequenced in both directions and deposited in GenBank (JX436358). Sequence analysis of the CP open reading frame (657 nt), conducted with MEGA5 software, revealed that the isolate 3-Lam showed the highest nucleotide identity of 99.4% (99.1% amino acid identity) with CMV isolates from Serbia, Australia, and the USA (GQ340670, U22821, and U20668, respectively). To our knowledge, this is the first report of the natural occurrence of CMV on L. maculatum worldwide and it adds a new host to over 1,241 species (101 plant families) infected by this virus (3). This is also an important discovery for the ornamental industry since L. maculatum is commonly grown together with other ornamental hosts of CMV in nurseries and the urban environment as well as in natural ecosystems. References: (1) Y. K. Chen et al. Arch. Virol. 146:1631, 2001. (2) M. L. Daughtrey et al. Plant Dis. 81:1220, 1997. (3) M. Jacquemond. Adv. Virus Res. 84:439, 2012. (4) I. Stankovic et al. Acta Virol. 55:337, 2011.


Antinociceptive effect of Butea monosperma on vincristine-induced neuropathic pain model in rats.
Neuropathic pain is a chronic neurodegenerative disease. It is well characterized by spontaneous pain, hyperalgesia, hypothesia, dysesthesia and allodynia. The present study was designed to investigate the antinociceptive potential of Butea monosperma on vincristine-induced painful neuropathy in rats. Vincristine was administered for induction of neuropathic pain in experimental animals. Hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal hyperalgesia, cold chemical allodynia, mechanical hyperalgesia and allodynia in the hind paw and tail thermal hyperalgesia, respectively, as an index of peripheral and central pain sensation. Tissue thiobarbituric acid reactive substances (TBARSs), reduced glutathione (GSH) and total calcium levels were estimated to assess the biochemical changes in the sciatic nerve tissue. Microscopically, histopathological changes were also observed in the sciatic nerve tissue. Ethanolic extract of B. monosperma leaves and pregabalin were administered for 14 consecutive days. Vincristine administration resulted in significant reduction in behavioural (i.e. hyperalgesia and allodynic pain sensation) changes along with a rise in the levels of TBARS, total calcium and decrease in GSH levels when compared with the normal control group. Moreover, significant histological changes were also observed. Pretreatment with B. monosperma significantly attenuated vincristine-induced development of painful behavioural, biochemical and histological changes in a dose-dependent manner, which is similar to that of pregabalin-pretreated group. B. monosperma ameliorated vincristine-induced painful neuropathy. It may be due to its potential of antioxidative, neuroprotective and calcium channel inactivation.


Inhibitor of kappa B epsilon (IκBε) is a non-redundant regulator of c-Rel-dependent gene expression in murine T and B cells.
Inhibitors of kappa B (IκBs) -α, -β and -ε effect selective regulation of specific nuclear factor of kappa B (NF-κB) dimers according to cell lineage, differentiation state or stimulus, in a manner that is not yet precisely defined. Lymphocyte antigen receptor ligation leads to degradation of all three IκBs but activation only of subsets of NF-κB-dependent genes, including those regulated by c-Rel, such as anti-apoptotic CD40 and BAFF-R on B cells, and interleukin-2 (IL-2) in T cells. We report that pre-culture of a mouse T cell line with tumour necrosis factor-α (TNF) inhibits IL-2 gene expression at the level of transcription through suppressive effects on NF-κB, AP-1 and NFAT transcription factor expression and function. Selective upregulation of IκBε and suppressed nuclear translocation of c-Rel were very marked in TNF-treated, compared to control cells, whether activated via T cell receptor (TCR) pathway or TNF receptor. IκBε associated with newly synthesised c-Rel in activated cells and, in contrast to IκBα and -β, showed enhanced association with p65/c-Rel in TNF-treated cells relative to controls. Studies in IκBε-deficient mice revealed that basal nuclear expression and nuclear translocation of c-Rel at early time-points of receptor ligation were higher in IκBε-/- T and B cells, compared to wild-type. IκBε-/- mice exhibited increased lymph node cellularity and enhanced basal thymidine incorporation by lymphoid cells ex vivo. IκBε-/- T cell blasts were primed for IL-2 expression, relative to wild-type. IκBε-/- splenic B cells showed enhanced survival ex vivo, compared to wild-type, and survival correlated with basal expression of CD40 and induced expression of CD40 and BAFF-R. Enhanced basal nuclear translocation of c-Rel, and upregulation of BAFF-R and CD40 occurred despite increased IκBα expression in IκBε-/- B cells. The data imply that regulation of these c-Rel-dependent lymphoid responses is a non-redundant function of IκBε.


SEIRD model to study the asymptomatic growth during COVID-19 pandemic in India.
According to the current perception, symptomatic, presymptomatic and asymptomatic infectious persons can infect the healthy population susceptible to the SARS-CoV-2. More importantly, various reports indicate that the number of asymptomatic cases can be several-fold higher than the reported symptomatic cases. In this article, we take the reported cases in India and various states within the country till September 1, as the specimen to understand the progression of the COVID-19. Employing a modified SEIRD model, we predict the spread of COVID-19 by the symptomatic as well as asymptomatic infectious population. Considering reported infection primarily due to symptomatic, we compare the model predicted results with the available data to estimate the dynamics of the asymptomatically infected population. Our data indicate that in the absence of the asymptomatic infectious population, the number of symptomatic cases would have been much less. Therefore, the current progress of the symptomatic infection can be reduced by quarantining the asymptomatically infectious population via extensive or random testing. This study is motivated strictly toward academic pursuit; this theoretical investigation is not meant for influencing policy decisions or public health practices.