[Physiophilosophical fundamentals and genesis of Tsigun, Indian, and Tibetan Yoga. Paramount empirical efficacy].
This article is devoted to the analysis of physiophilosophical fundamentals and genesis of Tsigun, Indian, and Tibetan Yoga based on the overview of the relevant literature with special reference to the methodology of these physical and mental disciplines and their therapeutic and health-giving efficacy. Based on the combination of physiophilosophical categories and medical knowledge in the framework of the concept of the five primary elements, the authors illustrate the development of the systemic approach by which ancient physicians related man to nature in order to derive the adaptation principle realized through human activities. Traditional and modern aspects of these activities are considered. In the traditional context, the performance of exercises as assigned by Tsigun, Indian, and Tibetan Yoga is considered as the purposeful realization of the energy of conscience for health improvement and development and in the modern context as the realization of a novel form of psychic creative capacity to the same effect based on fruitful brainwork.


Ganglioside regulation of AMPA receptor trafficking.
Gangliosides are major cell-surface determinants on all vertebrate neurons. Human congenital disorders of ganglioside biosynthesis invariably result in intellectual disability and are often associated with intractable seizures. To probe the mechanisms of ganglioside functions, affinity-captured ganglioside-binding proteins from rat cerebellar granule neurons were identified by quantitative proteomic mass spectrometry. Of the six proteins that bound selectively to the major brain ganglioside GT1b (GT1b:GM1 > 4; p < 10(-4)), three regulate neurotransmitter receptor trafficking: Thorase (ATPase family AAA domain-containing protein 1), soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (γ-SNAP), and the transmembrane protein Nicalin. Thorase facilitates endocytosis of GluR2 subunit-containing AMPA-type glutamate receptors (AMPARs) in an ATPase-dependent manner; its deletion in mice results in learning and memory deficits (J. Zhang et al., 2011b). GluR2-containing AMPARs did not bind GT1b, but bound specifically to another ganglioside, GM1. Addition of noncleavable ATP (ATPγS) significantly disrupted ganglioside binding, whereas it enhanced AMPAR association with Thorase, NSF, and Nicalin. Mutant mice lacking GT1b expressed markedly higher brain Thorase, whereas Thorase-null mice expressed higher GT1b. Treatment of cultured hippocampal neurons with sialidase, which cleaves GT1b (and other sialoglycans), resulted in a significant reduction in the size of surface GluR2 puncta. These data support a model in which GM1-bound GluR2-containing AMPARs are functionally segregated from GT1b-bound AMPAR-trafficking complexes. Release of ganglioside binding may enhance GluR2-containing AMPAR association with its trafficking complexes, increasing endocytosis. Disrupting ganglioside biosynthesis may result in reduced synaptic expression of GluR2-contianing AMPARs resulting in intellectual deficits and seizure susceptibility in mice and humans.


Better knowledge, better health: piloting an education intervention in chronic condition self-management support.
Chronic condition self-management and lifestyle risk modification education is paramount for General Practice registrars. A multi-dimensional learning package 'Better Knowledge, Better Health' was developed and piloted to improve General Practice registrars' understanding of their role in supporting chronic condition self-management in patients with osteoarthritis. This pilot study was supported by the Australian Better Health Initiative. Pre-training learning needs analysis with a new intake of General Practice registrars (n=40) indicated high levels of confidence in supporting patients in chronic condition management and lifestyle risk modification, and locating and interacting with local resources and allied health professionals. Conversely, interviews with General Practice Supervisors (n=13) found most would not identify chronic condition self-management skills as priorities for registrar learning. Supervisors were also not familiar with core principles of chronic condition self-management, in particular application of motivational interviewing to behaviour change. Disparities between General Practice Supervisors' perceptions of the importance of chronic condition self-management and lifestyle risk modification education and levels of access to learning opportunities in chronic condition self-management for registrars are discussed. Difficulties in implementing a pilot study within tight timeframes are also explored.


Use and misuse of the receiver operating characteristic curve in risk prediction.
The c statistic, or area under the receiver operating characteristic (ROC) curve, achieved popularity in diagnostic testing, in which the test characteristics of sensitivity and specificity are relevant to discriminating diseased versus nondiseased patients. The c statistic, however, may not be optimal in assessing models that predict future risk or stratify individuals into risk categories. In this setting, calibration is as important to the accurate assessment of risk. For example, a biomarker with an odds ratio of 3 may have little effect on the c statistic, yet an increased level could shift estimated 10-year cardiovascular risk for an individual patient from 8% to 24%, which would lead to different treatment recommendations under current Adult Treatment Panel III guidelines. Accepted risk factors such as lipids, hypertension, and smoking have only marginal impact on the c statistic individually yet lead to more accurate reclassification of large proportions of patients into higher-risk or lower-risk categories. Perfectly calibrated models for complex disease can, in fact, only achieve values for the c statistic well below the theoretical maximum of 1. Use of the c statistic for model selection could thus naively eliminate established risk factors from cardiovascular risk prediction scores. As novel risk factors are discovered, sole reliance on the c statistic to evaluate their utility as risk predictors thus seems ill-advised.


Inhibition by opioid agonists and enhancement by antagonists of the release of catecholamines from the dog adrenal gland in response to splanchnic nerve stimulation: evidence for the functional role of opioid receptors.
The aim of the present study is to examine how opioid agonists and antagonists modify the splanchnic nerve stimulation (SNS)-induced release of catecholamines from the dog adrenal gland in vivo, in an attempt to elucidate whether opioid receptors play a functional role in controlling catecholamine release. Output of epinephrine (EPI) and norepinephrine (NE) was determined from adrenal venous blood by using high-performance liquid chromatography with electrochemical detection. SNS (0.3, 1 and 3 Hz) produced increases in both EPI and NE output in a frequency-dependent manner. Leu-enkephalin (10-100 micrograms/kg i.v.) and morphine (10-100 micrograms/kg i.v.) attenuated the increase in EPI and NE output induced by 1 or 3 Hz of SNS without affecting the basal catecholamine output. A 25 to 40% reduction of the SNS-induced increase in catecholamine output was observed after the treatment with 100 micrograms/kg of leu-enkephalin or morphine. The increase in EPI and NE output induced by 1 and 3 Hz of SNS was enhanced markedly by naloxone (10-1000 micrograms/kg i.v.) and by naltrexone (10-1000 micrograms/kg i.v.). The SNS-induced increase in catecholamine output doubled after treatment with 100 and 1000 micrograms/kg of naloxone or naltrexone. Basal catecholamine output and the increase in output induced by 1 Hz of SNS were unaffected by naloxone or naltrexone. These results suggest that endogenously released opioid peptides inhibit the release of catecholamines by activating opioid receptors in the adrenal gland of the dog.


Nitric oxide synthase inhibitors protect against rotenone-induced, oxidative stress mediated parkinsonism in rats.
Rotenone is known to cause progressive dopaminergic neuronal loss in rodents, but it remains unclear how this mitochondrial complex-I inhibitor mediates neurodegeneration specific to substantia nigra pars compacta (SNpc). One of the proposed mechanisms is increased free radical generation owing to mitochondrial electron transport chain dysfunction following complex-I inhibition. The present study examined the role of nitric oxide (NO) and hydroxyl radicals (OH) in mediating rotenone-induced dopaminergic neurotoxicity. Indications of NO involvement are evidenced by inducible nitric oxide synthase (NOS) over-expression, and increased NADPH-diaphorase staining in SNpc neurons 96h following rotenone administration. Treatment of these animals with specific neuronal NOS inhibitor, 7-nitroindazole (7-NI) and non-specific NOS inhibitor, N-ω-nitro-l-argenine methyl ester (l-NAME) caused reversal of rotenone-induced striatal dopamine depletion, and attenuation of the neurotoxin-induced decrease in the number of tyrosine hydroxylase immunoreactive neurons in SNpc, as well as in apomorphine and amphetamine-induced unilateral rotations. Interestingly, the study also demonstrated the contribution of OH in mediating rotenone nigral toxicity since there appeared a significant generation of the reactive oxygen species in vivo 24h following rotenone administration, a copious loss of reduced and oxidized glutathione, and increased superoxide dismutase and catalase activities in the cytosolic fractions of the ipsilateral SNpc area on the 5th day. An OH scavenging capacity of 7-NI and l-NAME in a Fenton-like reaction, as well as complete reversal of the rotenone-induced increases in the antioxidant enzyme activities, and the loss in reduced and oxidized glutathione contents in the SNpc supported OH involvement in rotenone-induced dopaminergic neurotoxicity. While these results strongly suggest the contribution of both OH and NO, resulting in acute oxidative stress culminating in dopaminergic neurodegeneration caused by rotenone, the course of events indicated generation of OH as the primary event in the neurotoxic processes.


The correlation of gingival crevicular fluid interleukin-8 levels and periodontal status in localized juvenile periodontitis.
Localized juvenile periodontitis (LJP) is an early-onset periodontal disease characterized by progressive bone loss involving the permanent first molar and incisor teeth. Approximately 70% to 75% of LJP patients have impaired neutrophil chemotaxis towards a number of chemoattractants including N-formyl-methionyl-leucyl-phenyl-alanine, complement fragment C5a, leukotriene B4, and interleukin 8 (IL-8). The aim of the present study was to observe the role of IL-8 in the pathogenesis of LJP. Fourteen individuals who were systemically and periodontally healthy and 24 systemically healthy individuals diagnosed with LJP (based on the results of clinical periodontal assessments and radiographic examination) were recruited for this study. Gingival crevicular fluid (GCF) samples were obtained from anterior teeth in each subject before treatment. After evaluation of GCF amount from paper strips, enzyme-linked immunoabsorbent assay was employed to determine the amount of IL-8 in GCF. The amount and concentration of IL-8 measured was 894.5 +/- 435 pg, and 445.3 +/- 468 pg/microl for the experimental group and 747.3 +/- 543 pg and 684.7 +/- 548 pg/microl, for the control group. The correlation among the levels of cytokine and clinical parameters was assessed. It was observed that the concentration of IL-8 demonstrated a negative correlation with gingival index in the LJP group. In addition, no significant correlation was found among the total amount and concentration of IL-8, GCF volume, and clinical parameters in the control group. IL-8 is thought to enhance host defense mechanisms against gram-negative bacteria, thus providing protection against periodontal infections. Our data demonstrate that, when both the total amount and concentration of IL-8 are taken into consideration, no significant difference between LJP and healthy subjects is shown. This may indicate a less active IL-8 production compared with healthy subjects in spite of the dense Gram bacterial stimulation in LJP.


Characterization of plasmids conferring resistance to gentamicin and apramycin in strains of Salmonella typhimurium phage type 204c isolated in Britain.
In Salmonella typhimurium phage type 204c isolated in Britain, gentamicin resistance is specified by plasmids of the I1 compatibility group which also confer resistance to apramycin. These plasmids have been subdivided into three types within the I1 group on the basis of their antibiotic resistance specificity, their ability to produce colicin Ib and their restriction enzyme digest fragmentation patterns. All three have been identified in strains from cattle, but as yet only two types have been found in strains from humans. It is suggested that the use of apramycin in animal husbandry is responsible for the appearance of gentamicin resistance in multiresistant strains of phage type 204c, a phage type already epidemic in bovine animals and with an increasing incidence in humans.


Cetuximab in Patients with Non-Small Cell Lung Cancer and EGFR Exon 20 Insertion Alterations.
Epidermal Growth Factor Receptor (EGFR) exon 20 insertion alterations represent 4%-10% of all EGFR mutations in Non-Small Cell Lung Cancer (NSCLC) and result in resistance to standard EGFR-directed therapies. EGFR exon 20 insertions restrict the size of the kinase pocket, prohibiting the entry of approved EGFR kinase inhibitor drugs. Structural In Silico modeling also predicts that EGFR exon 20 insertion anomalies increase attractive electrostatic dimerization, hence stabilizing the activating dimer configuration. EGFR antibodies such as cetuximab that interfere with dimerization may lead to responses. We identified three non-smoking patients with NSCLC and EGFR exon 20 insertions treated with cetuximab-based therapy. All three patients demonstrated clinical benefit. A 58-year-old woman achieved prolonged stable disease lasting 9 months, while a 76-year-old woman and 38-year-old man maintained a partial response with progression-free survivals of 13 months and 32 months, respectively. In conclusion, cetuximab merits further investigation as it appears to be an additional promising therapy for overcoming EGFR exon 20 insertion-related resistance.


An ecological study of the determinants of differences in 2009 pandemic influenza mortality rates between countries in Europe.
Pandemic A (H1N1) 2009 mortality rates varied widely from one country to another. Our aim was to identify potential socioeconomic determinants of pandemic mortality and explain between-country variation. Based on data from a total of 30 European countries, we applied random-effects Poisson regression models to study the relationship between pandemic mortality rates (May 2009 to May 2010) and a set of representative environmental, health care-associated, economic and demographic country-level parameters. The study was completed by June 2010. Most regression approaches indicated a consistent, statistically significant inverse association between pandemic influenza-related mortality and per capita government expenditure on health. The findings were similar in univariable [coefficient: -0.00028, 95% Confidence Interval (CI): -0.00046, -0.00010, p = 0.002] and multivariable analyses (including all covariates, coefficient: -0.00107, 95% CI: -0.00196, -0.00018, p = 0.018). The estimate was barely insignificant when the multivariable model included only significant covariates from the univariate step (coefficient: -0.00046, 95% CI: -0.00095, 0.00003, p = 0.063). Our findings imply a significant inverse association between public spending on health and pandemic influenza mortality. In an attempt to interpret the estimated coefficient (-0.00028) for the per capita government expenditure on health, we observed that a rise of 100 international dollars was associated with a reduction in the pandemic influenza mortality rate by approximately 2.8%. However, further work needs to be done to unravel the mechanisms by which reduced government spending on health may have affected the 2009 pandemic influenza mortality.


Construction of a biocompatible decellularized porcine hepatic lobe for liver bioengineering.
One of the major obstacles in applying decellularized organs for clinical use is the recellularization step, during which huge numbers of cells are required to develop whole livers. We established a simple protocol for constructing a bioartificial hepatic lobe and investigated its biocompatibility. The right lateral lobe of porcine liver was decellularized using 0.1% sodium dodecyl sulfate through the right branch of the portal vein. Decellularized lobes were evaluated by histological and biochemical analyses. DNA content was quantified to validate the decellularization protocol. The presence of immunogenic and pathogenic antigens was checked to exclude potential rejection and thrombosis after xenotransplantation. Xeno-reactivity of decellularized tissue against human peripheral blood mononuclear cells was examined. Cytotoxicity was evaluated against hepatocarcinoma cells. Finally, scaffolds were incubated in collagenase for biodegradation testing. The decellularized lobe preserved the three-dimensional architecture, ultrastructure, extracellular matrix components, and vasculature. Scaffolds were almost depleted of DNA in addition to antigenic and pathogenic antigens, which are considered barriers to xenotransplantation. The human immune response against scaffolds was considered non-significant. Our matrices were biocompatible and biodegradable. We successfully developed a non-cytotoxic, non-immunogenic, and biodegradable porcine hepatic lobe for future liver regeneration and bioengineering.


Surgical treatment of osteoid osteoma in an adolescent.
The literature is complete in its review of osteoid osteoma and benign bone-forming tumors. When present in a child, the clinical and radiographic picture is not that clear and often is missed diagnosed. Routine radiographs may not offer a complete diagnosis in this young patient and additional studies are indicated. Tomograms and computerized tomographic (CT) scans, as well as bone scans, provide more information in determining the presence of absence of a bone lesion in the child. A case is presented of an 8-year-old female with pain for over 10 months, eventually diagnosed as an osteoid osteoma. A surgical procedure was performed to excise the lesion and replace it with a corticocancellous bone graft. The child has been followed for the past 5 years and has remained asymptomatic.


Molecular Mechanisms for CMT1A Duplication and HNPP Deletion.
As the best characterized human genomic disorders, 118 CMT1A and HNPP illustrate several common mechanistic features of genomic rearrangements. These features include the following: (1) Recombination occurs between homologous sequences flanking the duplicated/deleted genomic segment. (2) The evolution of the mammalian genome may result in an architecture consisting of region-specific low-copy repeats that predispose to rearrangement secondary to providing homologous regions as substrate for recombination. (3) Strand exchange occurs preferentially in a region of perfect sequence identity within the flanking repeat sequences. (4) Double-strand breaks likely initiate recombination between the flanking repeats. (5) The mechanism and rate of homologous recombination resulting in DNA rearrangement may differ for male and female gametogenesis. (6) Homologous recombination resulting in DNA rearrangement occurs with high frequency in the human genome. (7) Genomic disorders result from structural features of the human genome and not population specific alleles or founder effects; therefore, genomic disorders appear to occur with equal frequencies in different world populations.


SENCR stabilizes vascular endothelial cell adherens junctions through interaction with CKAP4.
SENCR is a human-specific, vascular cell-enriched long-noncoding RNA (lncRNA) that regulates vascular smooth muscle cell and endothelial cell (EC) phenotypes. The underlying mechanisms of action of SENCR in these and other cell types is unknown. Here, levels of SENCR RNA are shown to be elevated in several differentiated human EC lineages subjected to laminar shear stress. Increases in SENCR RNA are also observed in the laminar shear stress region of the adult aorta of humanized SENCR-expressing mice, but not in disturbed shear stress regions. SENCR loss-of-function studies disclose perturbations in EC membrane integrity resulting in increased EC permeability. Biotinylated RNA pull-down and mass spectrometry establish an abundant SENCR-binding protein, cytoskeletal-associated protein 4 (CKAP4); this ribonucleoprotein complex was further confirmed in an RNA immunoprecipitation experiment using an antibody to CKAP4. Structure-function studies demonstrate a noncanonical RNA-binding domain in CKAP4 that binds SENCR Upon SENCR knockdown, increasing levels of CKAP4 protein are detected in the EC surface fraction. Furthermore, an interaction between CKAP4 and CDH5 is enhanced in SENCR-depleted EC. This heightened association appears to destabilize the CDH5/CTNND1 complex and augment CDH5 internalization, resulting in impaired adherens junctions. These findings support SENCR as a flow-responsive lncRNA that promotes EC adherens junction integrity through physical association with CKAP4, thereby stabilizing cell membrane-bound CDH5.


Transformation of Uranyl Peroxide Studtite, [(UO2)(O2)(H2O)2](H2O)2, to Soluble Nanoscale Cage Clusters.
The dissolution behavior of uranyl peroxide studtite, [(UO2)(O2)(H2O)2](H2O)2, was examined under a wide range of alkaline aqueous environments with and without the addition of hydrogen peroxide. In the absence of added H2O2, studtite dissolved in aqueous solutions with a tetraethylammonium hydroxide to uranium molar ratio greater than 0.5, and the resulting species in solution characterized by Raman spectroscopy and electrospray ionization mass spectrometry (ESI-MS) is the uranyl peroxide nanocluster U24, [(UO2)(O2)(OH)]2424-. This is the first demonstration of the formation of uranyl peroxide nanoclusters from studtite in a solution lacking additional hydrogen peroxide. In similar systems containing added hydrogen peroxide (0.01 M - 1.0 M), studtite dissolved in solutions with a TEAOH to uranium ratio greater than 0.1, and the resulting uranyl peroxide species in solution was U28, [(UO2)(O2)1.5]2828-.


Repeated mRNA vaccination sequentially boosts SARS-CoV-2-specific CD8+ T cells in persons with previous COVID-19.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hybrid immunity is more protective than vaccination or previous infection alone. To investigate the kinetics of spike-reactive T (TS) cells from SARS-CoV-2 infection through messenger RNA vaccination in persons with hybrid immunity, we identified the T cell receptor (TCR) sequences of thousands of index TS cells and tracked their frequency in bulk TCRβ repertoires sampled longitudinally from the peripheral blood of persons who had recovered from coronavirus disease 2019 (COVID-19). Vaccinations led to large expansions in memory TS cell clonotypes, most of which were CD8+ T cells, while also eliciting diverse TS cell clonotypes not observed before vaccination. TCR sequence similarity clustering identified public CD8+ and CD4+ TCR motifs associated with spike (S) specificity. Synthesis of longitudinal bulk ex vivo single-chain TCRβ repertoires and paired-chain TCRɑβ sequences from droplet sequencing of TS cells provides a roadmap for the rapid assessment of T cell responses to vaccines and emerging pathogens.


Mumps outbreaks in Canada and the United States: time for new thinking on mumps vaccines.
Mumps epidemics in Canada and the United States prompted us to review evidence for the effectiveness of 5 different vaccine strains. Early trials with the Jeryl Lynn vaccine strain demonstrated an efficacy of approximately 95%, but in epidemic conditions, the effectiveness has been as low as 62%; this is still considerably better than the effectiveness of another safe strain, Rubini (which has an effectiveness of close to 0% in epidemic conditions). The Urabe vaccine strain has an effectiveness of 54%-87% but is prone to cause aseptic meningitis. Little epidemiological information is available for other vaccines. The Leningrad-Zagreb vaccine strain, which is widely used in developing countries and costs a fraction of what vaccines cost in the developed world, seems to have encouraging results; in 1 study, the effectiveness of this vaccine exceeded 95%. Aseptic meningitis has also been reported in association with this vaccine, but the benign nature of the associated meningitis was shown recently in Croatia. Also, the Leningrad-3 strain seems to be effective but causes less-benign meningitis. No mumps vaccine equals the best vaccines in quality, but the virtually complete safety of some strains may not offset their low effectiveness. Epidemiological data are pivotal in mumps, because serological testing is subject to many interpretation problems.


[Neurobiology of depression].
During decades, both aetiology and treatment in Depressive Disorders relied on neurotransmitters' physiopathology or on abnormalities in their receptors function. However, recently evidences from research on neurobiological grounds suggest that there are multiple and complex systems involved in the pathophysiology of Depressive Disorders. Several neurobiological structures, such as the neural, immune and endocrine systems seems to interact among themselves and to influence on clinical manifestations of illness. Moreover, dysregulations on lower levels, such as intracellular and genetic systems might cause anomalies in protein expression, and in consequence might modulate receptors' disfunction and disturbances at the intramolecular level of signal transmission. The above disturbances at different levels of complexity are finally integrated within the frame of most recent theoretical approaches to Depressive Disorders. Specifically, recent theories implicating neuronal plasticity and survival-death cell mechanisms are described. The aim of this review is to integrate recent evidence on pathophysiological mechanisms of Depressive Disorders. New lines of treatment based upon these 'new pathophysiology' of depression will be wellcome.


Prevalence of liver disease in veterans with bipolar disorder or schizophrenia.
To assess the prevalence of three liver diseases [hepatitis C virus (HCV), nonalcoholic fatty liver disease and alcohol-induced cirrhosis] in patients (veterans) with/without schizophrenia/schizoaffective disorder and bipolar disorder. A retrospective electronic chart review of Veterans Integrated Services Network 20 facilities from January 1, 2001 to December 21, 2006 selected patients to one of two groups: schizophrenia/schizoaffective disorder or bipolar disorder. Patients in both groups were compared with veterans in an equal-sized random sample from the same data set of veterans without psychiatric diagnoses. Logistic regression models evaluated risk for overall liver diseases as well as HCV, nonalcoholic fatty liver disease and alcoholic-induced cirrhosis. Patients with schizophrenia (n=6521) had a higher prevalence of liver disease [22.4% versus 3.2%; odds ratio (OR)=8.73]; HCV (16.5% versus 1.9%; OR=10.21); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=4.09) than matched controls. Patients with bipolar disorder (n=5319) had a higher prevalence of liver disease (21.5% versus 3.5%; OR=7.58); HCV (15.5% versus 2.1%; OR=8.60); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=3.82) than matched controls. Risk factors for liver disease in patients with schizophrenia (versus matched controls) included diabetes (OR=1.29), hypertension (OR=1.27), HIV (OR=3.54), substance use disorder (SUD) (OR=2.28), alcohol use disorder (OR=3.05) and schizophrenia (OR=2.74). Risk factors for development of liver disease for patients with bipolar disorder: diabetes (OR=1.40), HIV (OR=3.66), SUD (OR=2.68), alcohol use disorder (OR=3.22) and bipolar disorder (OR=2.27). This study in veterans shows that the presence of mental illness and its comorbidities represents a significant risk factor for the diagnosis of liver disease, including HCV and alcohol-related cirrhosis.


Nicotine and autoimmunity: The lotus' flower in tobacco.
Nicotine, the major component of cigarettes, has demonstrated conflicting impact on the immune system: some authors suggest that increases pro-inflammatory cytokines and provokes cellular apoptosis of neutrophils, releasing intracellular components that act as auto-antigens; others claimed that nicotine has a protective and anti-inflammatory effects, especially by binding to α7 subunit of nicotinic acetylcholine receptors. The cholinergic pathway contributes to an anti-inflammatory environment characterized by increasing T regulatory cells response, down-regulating of pro-inflammatory cytokines and a pro-inflammatory cells apoptosis. The effects of nicotine were studied in different autoimmune disease, as multiple sclerosis, type 1 diabetes, rheumatoid arthritis, sarcoidosis, Behçet's disease and inflammatory bowel diseases. The major problems about nicotine are the addiction and the adverse effects of related to each commercialized formulation. We sought in this review to summarize the knowledge accumulated to date concerning the relationship between nicotine and autoimmunity.


Effects of acute bouts of running and swimming exercise on PGC-1alpha protein expression in rat epitrochlearis and soleus muscle.
The purpose of this study was to elucidate the mechanisms underlying low-intensity exercise-induced peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) protein expression in rat skeletal muscles. Rats (5-6 wk old) swam without a load and ran on the treadmill at a speed of 13 m/min, respectively, in two 3-h sessions separated by 45 min of rest. PGC-1alpha content in epitrochlearis muscle (EPI) was increased by 75 and 95%, immediately and 6 h after swimming, respectively, with no increase in PGC-1alpha content in the soleus (SOL). After running, PGC-1alpha content in EPI was unchanged, whereas a 107% increase in PGC-1alpha content was observed in SOL 6 h after running. Furthermore, in EPI and SOL as well as other muscles (triceps, plantaris, red and white gastrocnemius), PGC-1alpha expression was enhanced concomitant with reduced glycogen postexercise, suggesting that expression of PGC-1alpha occurs in skeletal muscle recruited during exercise. PGC-1alpha content in EPI was increased after 18-h in vitro incubation with 0.5 mM 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and 4 mM caffeine. However, AICAR incubation did not affect PGC-1alpha content in the SOL, whereas caffeine incubation increased it. These results suggest that exercise-induced PGC-1alpha expression in skeletal muscle may be mediated by at least two exercise-induced signaling factors: AMPK activation and Ca2+ elevation. The number of factors involved (both AMPK and Ca2+, or Ca2+ only) in exercise-induced PGC-1alpha expression may differ among muscles.


Recombination occurs mainly between parental genomes and precedes DNA replication in pseudorabies virus-infected cells.
The experiments described in this paper were part of an attempt to determine the mechanisms involved in the isomerization of the pseudorabies virus genome. To this end, [(14)C]thymidine-labeled parental virus DNA that was transferred to progeny virions produced by cells incubated in medium containing bromodeoxy-uridine was analyzed in neutral and alkaline CsCl density gradients. The buoyant density of the (14)C-labeled DNA indicated that the parental DNA strands had retained their integrity and had not undergone breakage and reunion with progeny DNA strands; neither massive intermolecular nor intramolecular recombination had occurred after replication of the DNA. Whereas breakage and reunion between parental and progeny virus DNA strands were not detectable, these processes were observed between differentially density-labeled parental DNAs. Furthermore, the frequency of recombination between progeny DNAs accumulating in the cells was low. These results indicate that in pseudorabies virus-infected rabbit kidney cells recombination occurs mainly between parental genomes and precedes DNA replication. An analysis of the kinetics of appearance of recombinants between pairwise combinations of temperature-sensitive mutants also indicated that recombination is an early event. The ratio between the number of recombinant virions and the number of temperature-sensitive mutant virions produced by the cells remained the same throughout infection. Since the relative amounts of viral DNAs synthesized early and late during the infective process that were integrated into virions were approximately the same, it appears that late viral DNA did not experience an increased number of recombinational events compared with early viral DNA. These results, which reinforce the conclusion reached from the results of the analysis of the behavior of the parental DNA molecules in density shift experiments, indicate that recombination is an early event.


Study of wave propagation in discontinuous and heterogeneous media with the dynamic lattice method.
The development of a new dynamic lattice element method (dynamicLEM) as well as its application in the simulation of the propagation of body waves in discontinuous and heterogeneous media is the focus of this research paper. The conventional static lattice models are efficient numerical methods to simulate crack initiation and propagation in cemented geomaterials. The advantages of the LEM and the developed dynamic solution, such as simulation of arbitrary crack initiation and propagation, illustration and simulation of existing inherent material heterogeneity as well as stress redistribution upon crack opening, opens a new engineering field and tool for material analysis. To realize the time dependency of the dynamic LEM, the equation of motion of forced vibration is solved while using the Newmark-[Formula: see text] method and implementing the non-linear Newton-Raphson Jacobian method. The method validation is done according to the results of a boundary element method (BEM) in the plane P-SV-wave propagation within a plane strain domain. Further tests comparing the generated wave types, simulation and study of crack discontinuities as well as inherent heterogeneities in the geomaterials are conducted to illustrate the accurate applicability of the new dynamic lattice method. The results indicate that with increasing heterogeneity within the material, the wave field becomes significantly scattered and further analysis of wave fields according to the wavelength/heterogeneity ratio become indispensable. Therefore, in a heterogeneous medium, the application of continuum methods in relation to structural health monitoring should be precisely investigated and improved. The developed dynamic lattice element method is an ideal simulation tool to consider particle scale irregularities, crack distributions and inherent material heterogeneities and can be easily implemented in various engineering applications.


Safety and efficacy of endoscopist-directed balanced propofol sedation during endoscopic retrograde cholangiopancreatography.
Endoscopist-directed balanced propofol sedation (BPS) appears to be safe and effective for routine endoscopy. However, there are limited data on its use in endoscopic retrograde cholangiopancreatography (ERCP). We evaluated the safety and efficacy of endoscopist-directed BPS for ERCP, and compared patient outcomes with anesthesiologist-administered moderate sedation. This was a retrospective cohort study, using prospectively collected endoscopy data from a tertiary care medical center where endoscopist-directed BPS during ERCP is routine practice. Adverse outcomes included need for bag-mask ventilation or intubation, aborted ERCP due to sedation, hospital admission post-ERCP (outpatients)/change in the level of care (inpatients), and death within 24 h. A total of 501 patients underwent ERCP with the use of endoscopist-directed BPS: Cohort 1 - 380 (76%) inpatients, mean age 64.1, 46% male, 24% American Society of Anesthesiologists physical status (ASA) score I, 65% ASA II, 11% ASA III. Concurrently, 24 patients received anesthesiologist-administered moderate sedation: Cohort 2 - 19 (79%) inpatients, mean age 65.0, 67% male, 12% ASA I, 25% ASA II, 38% ASA III, 25% ASA IV. In Cohort 1, none of the adverse outcomes were observed. Propofol dose was inversely correlated with age (r=-0.42, P<0.001), ASA score (r=-0.19, P<0.001), and Mallampati score (r=-0.24, P<0.001). One patient in Cohort 2 who received anesthesiologist-administered BPS required bag-mask ventilation and the ERCP was prematurely aborted because of the sedation. There were no deaths from any cause within 24 h of ERCP. Endoscopist-directed BPS appears safe, efficacious, and feasible for ASA I-III patients undergoing inpatient or ambulatory ERCP.


The importance of marine vs. human-induced subsidies in the maintenance of an expanding mesocarnivore in the arctic tundra.
1. Most studies addressing the causes of the recent increases and expansions of mesopredators in many ecosystems have focused on the top-down, releasing effect of extinctions of large apex predators. However, in the case of the northward expansion of the red fox into the arctic tundra, a bottom-up effect of increased resource availability has been proposed, an effect that can counteract prey shortage in the low phase of the multi-annual rodent cycle. Resource subsidies both with marine and with terrestrial origins could potentially be involved. 2. During different phases of a multi-annual rodent cycle, we investigated the seasonal dynamics and spatial pattern of resource use by red foxes across a coast to inland low arctic tundra gradient, Varanger Peninsula, Norway. We employed two complementary methods of diet analyses: stomach contents and stable isotope analysis. 3. We found that inland red foxes primarily subsisted on reindeer carrions during the low phase of a small rodent population cycle. Lemmings became the most important food item towards the peak phase of the rodent cycle, despite being less abundant than sympatric voles. Isotopic signatures of tissue from both predator and prey also revealed that red foxes near the coast used marine-derived subsidies in the winter, but these allochthonous resources did not spillover to adult foxes living beyond 20-25 km from the coast. 4. Although more needs to be learned about the link between increasing primary productivity due to climatic warming and trophic dynamics in tundra ecosystems, we suggest that changes in reindeer management through a bottom-up effect, at least regionally, may have paved the way towards the establishment of a new mesopredator in the tundra biome.


Why Build a Robot With Artificial Consciousness? How to Begin? A Cross-Disciplinary Dialogue on the Design and Implementation of a Synthetic Model of Consciousness.
Creativity is intrinsic to Humanities and STEM disciplines. In the activities of artists and engineers, for example, an attempt is made to bring something new into the world through counterfactual thinking. However, creativity in these disciplines is distinguished by differences in motivations and constraints. For example, engineers typically direct their creativity toward building solutions to practical problems, whereas the outcomes of artistic creativity, which are largely useless to practical purposes, aspire to enrich the world aesthetically and conceptually. In this essay, an artist (DHS) and a roboticist (GS) engage in a cross-disciplinary conceptual analysis of the creative problem of artificial consciousness in a robot, expressing the counterfactual thinking necessitated by the problem, as well as disciplinary differences in motivations, constraints, and applications. We especially deal with the question of why one would build an artificial consciousness and we consider how an illusionist theory of consciousness alters prominent ethical debates on synthetic consciousness. We discuss theories of consciousness and their applicability to synthetic consciousness. We discuss practical approaches to implementing artificial consciousness in a robot and conclude by considering the role of creativity in the project of developing an artificial consciousness.


Patient-centredness, self-rated health, and patient empowerment: should providers spend more time communicating with their patients?
Patient-centred communication is often employed as a strategy for empowering patients. The purpose of this study was to investigate the relationship between a direct measure of patient empowerment, feeling that one is in control of one's own health and patient satisfaction with communication. A cross-sectional survey of family medicine patients was used to test the theory that, in primary care patients, empowerment is related to satisfaction with several aspects of communication after adjusting for health status, age and gender. Interviews were completed with 680 adult patients for whom complete data were available. Multiple logistic regression analysis revealed that being highly satisfied with overall communication [adjusted odds ratio (AOR)=2.08], explanations (AOR=2.04), listening (AOR=2.63), use of understandable words (AOR=2.41) and involvement in decisions (2.34) were positively associated with empowerment. Self-rated health was more strongly related to empowerment than satisfaction with communication in every model tested (AORs ranged from 2.8 to 3.0). Reliance solely on patient-centred communication to promote empowerment may be insufficient as well as costly. Instead, improved one-to-one communication between patients and providers should be reserved for clinically complex and urgent situations. For other health matters, referral of patients to community health promotion and education programmes should be considered because this may offer a lower-cost approach to empowerment.


Joint representation of translational and rotational components of optic flow in parietal cortex.
Terrestrial navigation naturally involves translations within the horizontal plane and eye rotations about a vertical (yaw) axis to track and fixate targets of interest. Neurons in the macaque ventral intraparietal (VIP) area are known to represent heading (the direction of self-translation) from optic flow in a manner that is tolerant to rotational visual cues generated during pursuit eye movements. Previous studies have also reported that eye rotations modulate the response gain of heading tuning curves in VIP neurons. We tested the hypothesis that VIP neurons simultaneously represent both heading and horizontal (yaw) eye rotation velocity by measuring heading tuning curves for a range of rotational velocities of either real or simulated eye movements. Three findings support the hypothesis of a joint representation. First, we show that rotation velocity selectivity based on gain modulations of visual heading tuning is similar to that measured during pure rotations. Second, gain modulations of heading tuning are similar for self-generated eye rotations and visually simulated rotations, indicating that the representation of rotation velocity in VIP is multimodal, driven by both visual and extraretinal signals. Third, we show that roughly one-half of VIP neurons jointly represent heading and rotation velocity in a multiplicatively separable manner. These results provide the first evidence, to our knowledge, for a joint representation of translation direction and rotation velocity in parietal cortex and show that rotation velocity can be represented based on visual cues, even in the absence of efference copy signals.


Scope and nature of sudden cardiac death before age 40 in Ontario: a report from the cardiac death advisory committee of the office of the chief coroner.
Understanding sudden cardiac death in the young may inform prevention strategies. To determine the scope and nature of sudden death in a geographically defined population. We performed a retrospective population-based cohort study in Ontario, Canada, of all sudden cardiac death cases involving persons aged 2-40 years identified from the 2008 comprehensive Coroner database. Of 1741 Coroner's cases, 376 were considered potential sudden cardiac death cases and underwent review. There were 174 cases of adjudicated sudden cardiac death from a population of 6,602,680 persons aged 2-40 years. Structural heart disease was present in 126 cases (72%), 78% of which was unrecognized. There was no identifiable cause of death in 48 cases (28%), representing primary arrhythmia syndromes. The majority of decedents were men (76%) over the age of 18 (90%). The overall incidence of sudden cardiac death increased with age from 0.7/100,000 (2-18 years) to 2.4/100,000 (19-29 years) to 5.3/100,000 (30-40 years) person-years. Persons experiencing sudden cardiac death before age 30 were more likely to have a primary arrhythmia syndrome (odds ratio 2.97; P<.001). The majority of events occurred in the home (72%); 33% of the events in children/adolescents and 9% of the events in adults occurred during reported moderate or vigorous exercise (P = .002). There were no pediatric deaths during organized competitive sports. The incidence of sudden cardiac death increases with age, typically occurring in a man at rest in the home with unrecognized underlying heart disease or a primary arrhythmia syndrome. Prevention strategies should consider targeting identification of unrecognized structural heart disease and primary arrhythmia syndromes.


Cognitive changes following surgery in intractable hemispheric and sub-hemispheric pediatric epilepsy.
The objectives were to study the short and longitudinal changes in the cognitive skills of children with intractable epilepsy after hemispheric/sub-hemispheric epilepsy surgery. Sixteen patients underwent surgery from September 2005 until March 2009. They underwent detailed presurgical evaluation of their cognitive skills and were repeated annually for 3 years. Their mean age was 6.6 years. Epilepsy was due to Rasmussen's encephalitis (n = 9), Infantile hemiplegia seizure syndrome (n = 2), hemimegalencephaly (n = 2), and Sturge Weber syndrome (n = 3). Fourteen (87.5%) patients underwent peri-insular hemispherotomy and two (12.5%) underwent peri-insular posterior quadrantectomy. The mental and social age, gross motor, fine motor, adaptive, and personal social skills showed a steady increase after surgery (p < 0.05). Language showed positive gains irrespective of the side and etiology of the lesion (p = 0.003). However, intelligence quotient (IQ) remained static on follow-up. Patients with acquired pathology gained more in their mental age, language, and conceptual thinking. Age of seizure onset and duration of seizures prior to surgery were predictive variables of postoperative cognitive skills. There are short- and long-term gains in the cognitive skills of children with intractable epilepsy after hemispherotomy and posterior quadrantectomy that was better in those patients with acquired diseases. Age of seizure onset and duration of seizures prior to surgery were independent variables that predicted the postoperative outcome.


Articular cartilage regeneration by activated skeletal stem cells.
Osteoarthritis (OA) is a degenerative disease resulting in irreversible, progressive destruction of articular cartilage1. The etiology of OA is complex and involves a variety of factors, including genetic predisposition, acute injury and chronic inflammation2-4. Here we investigate the ability of resident skeletal stem-cell (SSC) populations to regenerate cartilage in relation to age, a possible contributor to the development of osteoarthritis5-7. We demonstrate that aging is associated with progressive loss of SSCs and diminished chondrogenesis in the joints of both mice and humans. However, a local expansion of SSCs could still be triggered in the chondral surface of adult limb joints in mice by stimulating a regenerative response using microfracture (MF) surgery. Although MF-activated SSCs tended to form fibrous tissues, localized co-delivery of BMP2 and soluble VEGFR1 (sVEGFR1), a VEGF receptor antagonist, in a hydrogel skewed differentiation of MF-activated SSCs toward articular cartilage. These data indicate that following MF, a resident stem-cell population can be induced to generate cartilage for treatment of localized chondral disease in OA.


A double-blind, placebo-controlled trial of desipramine for primary alcohol dependence stratified on the presence or absence of major depression.
To assess the use of desipramine for secondary depression in primary alcohol dependence and its effect on abstinence. Randomized, double-blind, placebo-controlled trial, with stratification on the presence of secondary depression. Seventy-one volunteer and referred patients with primary alcohol dependence, abstinent a median of 8 days before randomization. A subset of 28 patients had major depression secondary to alcoholism. The outpatient psychiatry departments of two urban medical centers. Six months of a clinically determined dose of desipramine. Hamilton Depression Rating Scale, and Time Line Follow Back Interview, with breath alcohol concentrations and collateral verification. Hamilton Depression scores of desipramine-treated depressed alcoholics decreased significantly, controlling for baseline Hamilton Depression scores (P=.04). Overall, patients were abstinent significantly longer when receiving desipramine (P=.03). Rates of relapse of depressed vs nondepressed patients, analyzed separately, were not significant, although the survival function approached significance for the depressed subgroup (P=.09). Desipramine-treated depressed patients were more satisfied and were rated as more improved. Major depression secondary to alcohol dependence that is diagnosed after at least 1 week of abstinence can remain stable in some placebo-treated alcoholics and can respond to desipramine. Treating depression secondary to alcoholism may reduce risk for drinking relapse in some patients. Use of desipramine to reduce relapse in nondepressed alcoholics is not supported.


Effects of litter removal on the lipolytic response and the regulatory components of the adenylate cyclase in adipocytes isolated from lactating rats.
The effects of litter removal on the status of different components of the hormone-sensitive adenylate cyclase system were analysed in plasma membranes of rat adipocytes. These effects were correlated with the decreased lipolytic response of adipose tissue. No changes in total number of A1 adenosine receptors or their affinity were detected in response to litter removal. In contrast, beta-adrenergic receptors showed a decrease (35%) in total number of receptors, without any significant change in their affinity. The status of alpha-GS and alpha-Gi, the alpha-subunits of G proteins which mediate stimulation and inhibition respectively of adenylate cyclase, were probed by cholera- and pertussis-toxin-catalysed ADP-ribosylation respectively and by immunoblot. Associated with litter removal, decreases of 63% and 62% in the incorporation of [alpha 32P]ADP-ribose catalysed by cholera toxin and pertussis toxin into alpha-Gs and alpha-Gi respectively were detected. Immunoblotting using RM/1 (anti-alpha-Gs) and AS/7 (anti-alpha-Gi) antisera also showed decreases in the levels of alpha-Gs (52%) and alpha-Gi (55%) in adipocyte membranes from litter-removed rats compared with lactating rats. Alterations in the status of hormone-sensitive adenylate cyclase components, such as those described herein, may be biochemical mechanism(s) by which adipose tissue shows a decreased lipolytic response during recovery from lactation.


Calculation of mean cell residence time for unsteady-state activated sludge systems.
A formulation to calculate the mean cell residence time (MCRT or sludge age) of unsteady-state activated sludge systems is presented. The formulation was studied by applying it to data generated by computer simulation and to data obtained from an actual wastewater treatment plant. The computer simulation study allowed the effects of step and pulse changes in biochemical oxygen demand (BOD) loading, and step changes in a control variable, waste sludge flow rate, to be studied independently of each other and of other disturbances. The unsteady-state MCRT formulation (herein called the dynamic sludge age, or DSA) was found to be an improvement over the traditional steady-state calculation, both for process control, and for research into activated sludge dynamics.


[Effect of Panax ginseng components on the differentiation of mouse embryonic stem cells into cardiac-like cells].
Bioactive compounds that may control the specific differentiation from mouse embryonic stem (ES) cells into cardiac-like cells have been screened from herbal medicines. Among seven preparations, Panax ginseng was found to promote the differentiation into beating cells and to sustain their beating for longer than the control. Active compounds were found in its water-soluble fraction. Although they were not isolated, their candidates were surveyed in 42 compounds selected from the database of P. ginseng. Finally we found that vitamin B12 (VB12) and methionine were active. VB12 accelerated the differentiation into beating cells and made the beating rate constantly 100%. Moreover, VB12 was effective in the recovery of beating that was inhibited by spermine action. The mechanism of action of VB12 is discussed in termo of the relevance of intercellular electrical signal transduction.


Thermoneutral Housing Enables Studies of Vertical Transmission of Obesogenic Diet-Driven Metabolic Diseases.
Vertical transmission of obesity is a critical contributor to the unabated obesity pandemic and the associated surge in metabolic diseases. Existing experimental models insufficiently recapitulate "human-like" obesity phenotypes, limiting the discovery of how severe obesity in pregnancy instructs vertical transmission of obesity. Here, via utility of thermoneutral housing and obesogenic diet feeding coupled to syngeneic mating of WT obese female and lean male mice on a C57BL/6 background, we present a tractable, more "human-like" approach to specifically investigate how maternal obesity contributes to offspring health. Using this model, we found that maternal obesity decreased neonatal survival, increased offspring adiposity, and accelerated offspring predisposition to obesity and metabolic disease. We also show that severe maternal obesity was sufficient to skew offspring microbiome and create a proinflammatory gestational environment that correlated with inflammatory changes in the offspring in utero and adulthood. Analysis of a human birth cohort study of mothers with and without obesity and their infants was consistent with mouse study findings of maternal inflammation and offspring weight gain propensity. Together, our results show that dietary induction of obesity in female mice coupled to thermoneutral housing can be used for future mechanistic interrogations of obesity and metabolic disease in pregnancy and vertical transmission of pathogenic traits.


Carcinoma of paranasal sinuses: long-term outcomes with radiotherapy.
To assess the clinical features, prognostic factors, results, and complications of treatment of carcinomas of the paranasal sinus. The records of 106 patients (72 men and 34 women) with paranasal sinus carcinoma treated with curative intent at Washington University between January 1960 and August 1998 were analyzed. Patient age ranged from 29 to 91 years (median, 64 years). Most tumors originated in the maxillary (76%) or ethmoid (18%) sinus. Most tumors were locally advanced at presentation. All patients underwent radiotherapy (RT), combined with surgery in 65%; 2% received chemotherapy. Follow-up ranged from 1.7 months to 24 years (median 5 years). The 5-year local tumor control, locoregional tumor control, disease-free survival (DFS), and overall survival rate was 58%, 39%, 33%, and 27%, respectively. A statistically significant improvement in DFS was noted with the addition of surgical resection to RT (35% vs. 29%, p = 0.05). Nodal status at presentation emerged as a statistically significant predictor for locoregional tumor control and DFS in multivariate analysis. Distant metastases occurred in 29% of patients. This review of a large, single-institution experience of paranasal sinus carcinoma patients who underwent RT showed that locoregional tumor progression and recurrence remain predominant patterns of failure despite aggressive local treatment with combined surgery and RT. DFS improved slightly with combined modality treatment. The overall survival rates remained suboptimal, suggesting a need for more accurate determination of tumor extent, as well as more effective locoregional and systemic therapies.


Effect of Concentration on the Electrochemistry and Speciation of the Magnesium Aluminum Chloride Complex Electrolyte Solution.
Magnesium batteries offer an opportunity to use naturally abundant Mg and achieve large volumetric capacities reaching over four times that of conventional Li-based intercalation anodes. High volumetric capacity is enabled by the use of a Mg metal anode in which charge is stored via electrodeposition and stripping processes, however, electrolytes that support efficient Mg electrodeposition and stripping are few and are often prepared from highly reactive compounds. One interesting electrolyte solution that supports Mg deposition and stripping without the use of highly reactive reagents is the magnesium aluminum chloride complex (MACC) electrolyte. The MACC exhibits high Coulombic efficiencies and low deposition overpotentials following an electrolytic conditioning protocol that stabilizes species necessary for such behavior. Here, we discuss the effect of the MgCl2 and AlCl3 concentrations on the deposition overpotential, current density, and the conditioning process. Higher concentrations of MACC exhibit enhanced Mg electrodeposition current density and much faster conditioning. An increase in the salt concentrations causes a shift in the complex equilibria involving both cations. The conditioning process is strongly dependent on the concentration suggesting that the electrolyte is activated through a change in speciation of electrolyte complexes and is not simply due to the annihilation of electrolyte impurities. Additionally, the presence of the [Mg2(μ-Cl)3·6THF]+ in the electrolyte solution is again confirmed through careful analysis of experimental Raman spectra coupled with simulation and direct observation of the complex in sonic spray ionization mass spectrometry. Importantly, we suggest that the ∼210 cm-1 mode commonly observed in the Raman spectra of many Mg electrolytes is indicative of the C3v symmetric [Mg2(μ-Cl)3·6THF]+. The 210 cm-1 mode is present in many electrolytes containing MgCl2, so its assignment is of broad interest to the Mg electrolyte community.


Development of mPing-based activation tags for crop insertional mutagenesis.
Modern plant breeding increasingly relies on genomic information to guide crop improvement. Although some genes are characterized, additional tools are needed to effectively identify and characterize genes associated with crop traits. To address this need, the mPing element from rice was modified to serve as an activation tag to induce expression of nearby genes. Embedding promoter sequences in mPing resulted in a decrease in overall transposition rate; however, this effect was negated by using a hyperactive version of mPing called mmPing20. Transgenic soybean events carrying mPing-based activation tags and the appropriate transposase expression cassettes showed evidence of transposition. Expression analysis of a line that contained a heritable insertion of the mmPing20F activation tag indicated that the activation tag induced overexpression of the nearby soybean genes. This represents a significant advance in gene discovery technology as activation tags have the potential to induce more phenotypes than the original mPing element, improving the overall effectiveness of the mutagenesis system.


Diffusion abnormalities in pediatric mild traumatic brain injury.
Pediatric mild traumatic brain injury (pmTBI) is the most prevalent neurological insult in children and is associated with both acute and chronic neurobehavioral sequelae. However, little is known about underlying pathophysiology and how injuries change as a function of recovery. Fractional anisotropy, axial diffusivity, and radial diffusivity were examined in 15 semi-acute pmTBI patients and 15 well-matched controls, with a subset of participants returning for a second visit. A novel analytic strategy was applied to capture spatially heterogeneous white matter injuries (lesions) in addition to standard analyses. Evidence of cognitive dysfunction after pmTBI was observed in the domains of attention (p = 0.02, d = -0.92) and processing speed (p = 0.05, d = -0.73) semi-acutely. Region of interest (ROI) and voxelwise analyses indicated increased anisotropic diffusion for pmTBI patients, with an elevated number of clusters with high anisotropy. Metrics of increased anisotropy were able to objectively classify pmTBI from healthy controls at 90% accuracy but were not associated with neuropsychological deficits. Little evidence of recovery in white matter abnormalities was observed over a 4-month interval in returning patients, indicating that physiological recovery may lag behind subjective reports of normality. Increased anisotropic diffusion has been previously linked with cytotoxic edema after TBI, and the magnitude and duration of these abnormalities appear to be greater in pediatric patients. Current findings suggest that developing white matter may be more susceptible to initial mechanical injury forces and that anisotropic diffusion provides an objective biomarker of pmTBI.


Deoxydehydration of polyols catalyzed by a molybdenum dioxo-complex supported by a dianionic ONO pincer ligand.
Deoxydehydration (DODH) is the net reduction of diols and polyols to alkenes or dienes and water. Molybdenum cis-dioxo bis-phenolate ONO complexes were synthesized and have been shown to be active for DODH. Catalysts were screened for activity at 150-190 °C, and appreciable yields of up to 59% were obtained. PPh3, Na2SO3, Zn, C, 3-octanol and 2-propanol were screened as reductants. Additionally, the reactivities of a variety of diols were screened. With (R,R)-(+)-hydrobenzoin as substrate, DODH occurs via a mechanism where reduction of the Mo catalyst is a result of diol oxidation to form two equivalents of aldehyde. These reactions result in complete conversion and near quantitative yields of trans-stilbene and benzaldehyde.


Spatial Allocation and Specification of Cardiomyocytes during Zebrafish Embryogenesis.
Incomplete development and severe malformation of the heart result in miscarriage of embryos because of its malfunction as a pump for circulation. During cardiogenesis, development of the heart is precisely coordinated by the genetically-primed program that is revealed by the sequential expression of transcription factors. It is important to investigate how spatial allocation of the heart containing cardiomyocytes and other mesoderm-derived cells is determined. In addition, the molecular mechanism underlying cardiomyocyte differentiation still remains elusive. The location of ectoderm-, mesoderm-, and endoderm-derived organs is determined by their initial allocation and subsequent mutual cell-cell interactions or paracrine-based regulation. In the present work, we provide an overview of cardiac development controlled by the germ layers and discuss the points that should be uncovered in future for understanding cardiogenesis.


The frequency-response electroretinogram distinguishes cone and abnormal rod function in rd12 mice.
Early studies on Rpe65 knockout mice reported that remaining visual function was attributable to cone function. However, this finding has been challenged more and more as time has passed. Electroretinograms (ERGs) showed that rd12 mice, a spontaneous animal model of RPE65 Leber's congenital amaurosis, had sizeable photopic responses. Unfortunately, the recorded ERG waveform was difficult to interpret because of a remarkably delayed peak-time, which resembles a rod response more than a cone response. Here, we compare flicker ERGs in animals with normal rod and cone function (C57BL/6J mice), pure rod function (cpfl5 mice), and pure cone function (Rho(-/-) mice) under different adaptation levels and stimulus intensities. These responses were then compared with those obtained from rd12 mice. Our results showed that normal rods respond to low frequency flicker (5 and 15 Hz) and that normal cones respond to both low and high frequency flicker (5-35 Hz). As was seen in cpfl5 mice, rd12 mice had recordable responses to low frequency flicker (5 and 15Hz), but not to high frequency flicker (25 and 35 Hz). We hypothesize that abnormal rods may be the source of residual vision in rd12 mice, which is proved correct here with double mutant rd12mice. In this study, we show, for the first time, that frequency-response ERGs can effectively distinguish cone- and rod-driven responses in the rd12 mouse. It is another simple and valid method for evaluating the respective contributions of retinal rods and cones.


Karyotypes of water frogs from the Pelophylax esculentus complex: results of cross-species chromosomal painting.
Amphibian species have the largest genome size enriched with repetitive sequences and relatively similar karyotypes. Moreover, many amphibian species frequently hybridize causing nuclear and mitochondrial genome introgressions. In addition, hybridization in some amphibian species may lead to clonality and polyploidization. All such events were found in water frogs from the genus Pelophylax. Among the species within the genus Pelophylax, P. esculentus complex is the most widely distributed and well-studied. This complex includes two parental species, P. ridibundus and P. lessonae, and their hybrids, P. esculentus, reproducing hemiclonally. Parental species and their hybrids have similar but slightly polymorphic karyotypes, so their precise identification is still required. Here, we have developed a complete set of 13 chromosome painting probes for two parental species allowing the precise identification of all chromosomes. Applying chromosomal painting, we identified homologous chromosomes in both parental species and orthologous chromosomes in their diploid hemiclonal hybrids. Comparative painting did not reveal interchromosomal exchanges between the studied water frog species and their hybrids. Using cross-specific chromosome painting, we detected unequal distribution of the signals along chromosomes suggesting the presence of species-specific tandem repeats. Application of chromosomal paints to the karyotypes of hybrids revealed differences in the intensity of staining for P. ridibundus and P. lessonae chromosomes. Thus, both parental genomes have a divergence in unique sequences. Obtained chromosome probes may serve as a powerful tool to unravel chromosomal evolution in phylogenetically related species, identify individual chromosomes in different cell types, and investigate the elimination of chromosomes in hybrid water frogs.


Effect of ocean outfall discharge volume and dissolved inorganic nitrogen load on urban eutrophication outcomes in the Southern California Bight.
Climate change is increasing drought severity worldwide. Ocean discharges of municipal wastewater are a target for potable water recycling. Potable water recycling would reduce wastewater volume; however, the effect on mass nitrogen loading is dependent on treatment. In cases where nitrogen mass loading is not altered or altered minimally, this practice has the potential to influence spatial patterns in coastal eutrophication. We apply a physical-biogeochemical numerical ocean model to understand the influence of nitrogen management and potable wastewater recycling on net primary productivity (NPP), pH, and oxygen. We model several theoretical management scenarios by combining dissolved inorganic nitrogen (DIN) reductions from 50 to 85% and recycling from 0 to 90%, applied to 19 generalized wastewater outfalls in the Southern California Bight. Under no recycling, NPP, acidification, and oxygen loss decline with DIN reductions, which simulated habitat volume expansion for pelagic calcifiers and aerobic taxa. Recycling scenarios under intermediate DIN reduction show patchier areas of pH and oxygen loss with steeper vertical declines relative to a "no recycling" scenario. These patches are diminished under 85% DIN reduction across all recycling levels, suggesting nitrogen management lowers eutrophication risk even with concentrated discharges. These findings represent a novel application of ocean numerical models to investigate the regional effects of idealized outfall management on eutrophication. Additional work is needed to investigate more realistic outfall-specific water recycling and nutrient management scenarios and to contextualize the benefit of these management actions, given accelerating acidification and hypoxia from climate change.


Identification of Proteins Required for Precise Positioning of Apc2 in Dendrites.
In Drosophila neurons, uniform minus-end-out polarity in dendrites is maintained in part by kinesin-2-mediated steering of growing microtubules at branch points. Apc links the kinesin motor to growing microtubule plus ends and Apc2 recruits Apc to branch points where it functions. Because Apc2 acts to concentrate other steering proteins to branch points, we wished to understand how Apc2 is targeted. From an initial broad candidate RNAi screen, we found Miro (a mitochondrial transport protein), Ank2, Axin, spastin and Rac1 were required to position Apc2-GFP at dendrite branch points. YFP-Ank2-L8, Axin-GFP and mitochondria also localized to branch points suggesting the screen identified relevant proteins. By performing secondary screens, we found that energy production by mitochondria was key for Apc2-GFP positioning and spastin acted upstream of mitochondria. Ank2 seems to act independently from other players, except its membrane partner, Neuroglian (Nrg). Rac1 likely acts through Arp2/3 to generate branched actin to help recruit Apc2-GFP. Axin can function in a variety of wnt signaling pathways, one of which includes heterotrimeric G proteins and Frizzleds. Knockdown of Gαs, Gαo, Fz and Fz2, reduced targeting of Apc2 and Axin to branch points. Overall our data suggest that mitochondrial energy production, Nrg/Ank2, branched actin generated by Arp2/3 and Fz/G proteins/Axin function as four modules that control localization of the microtubule regulator Apc2 to its site of action in dendrite branch points.


Attenuated sympathetic nerve responses after 24 hours of bed rest.
Bed rest reduces orthostatic tolerance. Despite decades of study, the cause of this phenomenon remains unclear. In this report we examined hemodynamic and sympathetic nerve responses to graded lower body negative pressure (LBNP) before and after 24 h of bed rest. LBNP allows for baroreceptor disengagement in a graded fashion. We measured heart rate (HR), cardiac output (HR x stroke volume obtained by echo Doppler), and muscle sympathetic nerve activity (MSNA) during a progressive and graded LBNP paradigm. Negative pressure was increased by 10 mmHg every 3 min until presyncope or completion of -60 mmHg. After bed rest, LBNP tolerance was reduced in 11 of 13 subjects (P <.023), HR was greater (P <.002), cardiac output was unchanged, and the ability to augment MSNA at high levels of LBNP was reduced (rate of rise for 30- to 60-mmHg LBNP before bed rest 0.073 bursts x min(-1) x mmHg(-1); after bed rest 0.035 bursts x min(-1) x mmHg(-1); P < 0.016). These findings suggest that 24 h of bed rest reduces sympathetic nerve responses to LBNP.


Evaluating the sport scuba diver.
When evaluating an individual planning to scuba-dive, search for conditions that increase the risk of a diving accident. These risks can be categorized as absolute, relative or temporary. An understanding of barotrauma and decompression sickness is essential. The psychologic examination is as important as the determination of physical fitness.


A new model for in vitro testing of vitreous substitute candidates.
To describe a new model for in vitro assessment of novel vitreous substitute candidates. The biological impact of three vitreous substitute candidates was explored in a retinal explant culture model; a polyalkylimide hydrogel (Bio-Alcamid®), a two component hydrogel of 20 wt.% poly (ethylene glycol) in phosphate buffered saline (PEG) and a cross-linked sodium hyaluronic acid hydrogel (Healaflow®). The gels where applied to explanted adult rat retinas and then kept in culture for 2, 5 and 10 days. Gel-exposed explants were compared with explants incubated under standard tissue culture conditions. Cryosections of the specimens were stained with hematoxylin and eosin, immunohistochemical markers (GFAP, Vimentin, Neurofilament 160, PKC, Rhodopsin) and TUNEL. Explants kept under standard conditions as well as PEG-exposed explants displayed disruption of retinal layers with moderate pyknosis of all neurons. They also displayed moderate labeling of apoptotic cells. Bio-Alcamid®-exposed explants displayed severe thinning and disruption of retinal layers with massive cell death. Healaflow®-treated explants displayed normal retinal lamination with significantly better preservation of retinal neurons compared with control specimens, and almost no signs of apoptosis. Retinas exposed to Healaflow® and retinas kept under standard conditions showed variable labeling of GFAP with generally low expression and some areas of upregulation. PEG-exposed retinas showed increased GFAP labeling and Bio-Alcamid®-exposed retinas showed sparse labeling of GFAP. Research into novel vitreous substitutes has important implications for both medical and surgical vitreoretinal disease. The in vitro model presented here provides a method of biocompatibility testing prior to more costly and cumbersome in vivo experiments. The explant culture system imposes reactions within the retina including disruption of layers, cell death and gliosis, and the progression of these reactions can be used for comparison of vitreous substitute candidates. Bio-Alcamid® had strong adverse effects on the retina which is consistent with results of prior in vivo trials. PEG gel elicits reactions similar to the control retinas whereas Healaflow® shows protection from culture-induced trauma indicating favorable biocompatibility.


[Digestion of pea and soya proteins in the preruminant calf. I. Circulating levels of nutrients, antibody formation and intestinal permeability to macromolecules].
Three milk-substitutes (control, pea and soya-bean)were given to 6 preruminant calves. In the control diet protein was almost entirely provided by skim milk powder. In the pea diet a pregelatinized dehulled pea flour provided 33.5% of the protein, the remainder being supplied by skim milk powder. In the soya-bean diet, 73.2% of the protein were provided by a soya-bean isolate and the remainder by whey powder. The concentrations of plasma triglycerides and the free alpha-amino nitrogen in the peripheral blood were lower with the pea and soya-bean diets than with the control diet before the morning meal, but became higher after feeding. That suggested a faster abomasal emptying of fat and protein with the pea and especially the soya-bean diet. Systemic antibody responses were induced against pea protein but not against soya-bean protein. No effect of the diet on the plasma concentration of immunoreactive beta-lactoglobulin was apparent after 6 days, suggesting there was no important change in gut permeability at least at that time.


Efficacy of a Human Papillomavirus Vaccination Educational Platform in a Diverse Urban Population.
Human papillomavirus (HPV) is a preventable disease that plays a causative role in a significant proportion of malignant neoplasms of the head and neck. Inner-city populations are at risk for HPV-related oropharyngeal cancer, are least likely to receive HPV vaccination, and report a lack of information regarding HPV. To determine whether an educational platform affects knowledge, attitudes, and practices regarding HPV vaccination in an inner-city community. This prospective cohort study, conducted from March 1 to December 31, 2014, surveyed 128 participants at multiple inner-city community centers regarding their knowledge of, attitudes toward, and practices regarding HPV vaccination before and after a brief educational presentation. No eligible individuals refused to participate in the educational session. Surveys were excluded from analysis if they were incomplete. Participants completed two 20-question surveys separated by a 15-minute educational session on HPV-related disease, including a short PowerPoint presentation. Presence of statistically significant differences in survey scores before and after the educational session. Eighty-six participants met eligibility criteria (61 male [70.9%]; 68 with a high school education [79.1%]). Baseline knowledge of HPV, its causal association with cancer, and the existence of a vaccine against HPV were poor: of a total composite score of 20, the mean knowledge score before the educational session was 9.69. Participants' self-rated knowledge regarding HPV disease and vaccination improved significantly as a result of the educational session; the absolute increase in mean knowledge composite score from before the educational session to after the session was 3.52 (17.6%) (95% CI, -2.87 to 9.92; P < .01). Attitudes regarding government involvement in vaccination did not change as a result of the educational session (composite attitudes score before the educational session, 16.57 of 28; score after the session, 15.22; P = .98). Participants' intent to vaccinate their children increased significantly following the educational presentation: before the presentation, 34 respondents (40%) intended to have their children vaccinated; after the presentation, 60 (70%) intended to do so (P = .002). Lack of knowledge regarding HPV vaccination and unwillingness to undergo vaccination contribute to low rates of HPV vaccination within urban populations. Community-based educational sessions successfully teach the link between HPV and various cancers, provide information regarding the risks and benefits of vaccination, and increase participants' willingness to vaccinate their children against HPV. Attitudes regarding government involvement in health programs are resistant to change.


A biological blueprint for the axons of superficial layer pyramidal cells in cat primary visual cortex.
Pyramidal cells in the superficial layers of neocortex of higher mammals form a lateral network of axon clusters known as the 'daisy' network. The role of these axon clusters remains speculative and we still lack a comprehensive quantitative description of the single neurons forming the daisy or their heterogeneity. We filled intracellularly 50 superficial layer pyramidal neurons in the cat primary visual cortex and reconstructed the axonal tree and their synaptic boutons in 3D. Individual bouton clusters were identified using an objective mean-shift algorithm. By parameterizing the morphology of these 50 axonal trees and the 217 bouton clusters they formed, we were able to extract one set of relatively constant parameters and another set of variable parameters. Both sets combined allowed us to outline a comprehensive biological blueprint of superficial layer pyramidal neurons. Overall, our detailed analysis supports the hypothesis that pyramidal neurons use their lateral clusters to combine differential contextual cues, required for context-dependent processing of natural scenes.


Global Assessment of Mendelian Stroke Genetic Prevalence in 101 635 Individuals From 7 Ethnic Groups.
Background and Purpose- Mendelian stroke confers a high lifetime risk for mutation carriers; however, ethnicity-specific prevalence estimates have been difficult to establish. Methods- Eighteen genes responsible for Mendelian stroke were investigated using the Genome Aggregation Database. Genome Aggregation Database participants belonged to 1 of 7 populations: African/African-American, Latino/Admixed American, Ashkenazi Jewish, East Asian, Finnish European, non-Finnish European, and South Asian. Rare nonsynonymous variants from 101 635 participants free of neurological disease were examined for each ethnicity. Mutations were categorized according to 3 nested classes: pathogenic clinical variants, likely damaging variants based on in silico prediction, and all nonsynonymous variants. Results- ABCC6, KRIT1, CECR1, COL3A1, COL4A1, COL4A2, COLGALT1, GLA, HTRA1, NOTCH3, RNF213, and TREX1 harbored pathogenic clinical variants in Genome Aggregation Database. Across all 18 genes, total nonsynonymous carrier frequency was found to be high in 5 ethnicities (African/African-American, Latino/Admixed American, East Asian, non-Finnish European, and South Asian; 28.5%-37.5%) while lower total frequencies were estimated for in silico-predicted likely damaging variants (14.9%-19.7%) and pathogenic clinical variants (0.7%-2.8%). Overall, East Asian exhibited the highest total pathogenic clinical mutation carrier frequency (2.8%). ABCC6 pathogenic clinical variants were most prevalent among East Asian (0.8%). Pathogenic NOTCH3 variants, causal for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, were most frequent among East Asian (1.1%) and South Asian (1.2%). East Asian also demonstrated the highest carrier rate for RNF213 (0.8%). Finnish European exhibited the greatest HTRA1 frequency (0.2%), while COL4A1 pathogenic variants were most prevalent in African/African-American (0.3%). Conclusions- Especially, among pathogenic clinical variants, Mendelian stroke genetic prevalence differed significantly between populations. These prevalence estimates may serve as guides for screening and risk profiling in patients worldwide, particularly for understudied non-European populations.


The CIDI-core substance abuse and dependence questions: cross-cultural and nosological issues. The WHO/ADAMHA Field Trial.
The CIDI is a fully standardised, structured interview for the assessment of psychiatric disorders according to DSM-III-R and proposed ICD-10 criteria. The development of this interview has been the collaborative effort of researchers from 18 sites around the world. In a field trial to test the cross-cultural acceptability and reliability of the questions, there was found to be high acceptance and excellent reliability for the substance use questions, problems with the lengthy alcohol section, and difficulties translating relevant substance use concepts into different languages. There is therefore room for further improvement in the substance-related questions. There proved to be differences between ICD-10 and DSM-III-R regarding substance abuse and dependence disorders.


First report from the American College of Surgeons Bariatric Surgery Center Network: laparoscopic sleeve gastrectomy has morbidity and effectiveness positioned between the band and the bypass.
To assess the safety and effectiveness of the laparoscopic sleeve gastrectomy (LSG) as compared to the laparoscopic adjustable gastric band (LAGB), the laparoscopic Roux-en-Y gastric bypass (LRYGB) and the open Roux-en-Y gastric bypass (ORYGB) for the treatment of obesity and obesity-related diseases. LSG is a newer procedure being done with increasing frequency. However, limited data are currently available comparing LSG to the other established procedures. We present the first prospective, multiinstitutional, nationwide, clinically rich, bariatric-specific data comparing sleeve gastrectomy to the adjustable gastric band, and the gastric bypass. This is the initial report analyzing data from the American College of Surgeons-Bariatric Surgery Center Network accreditation program, and its prospective, longitudinal, data collection system based on standardized definitions and collected by trained data reviewers. Univariate and multivariate analyses compare 30-day, 6-month, and 1-year outcomes including morbidity and mortality, readmissions, and reoperations as well as reduction in body mass index (BMI) and weight-related comorbidities. One hundred nine hospitals submitted data for 28,616 patients, from July, 2007 to September, 2010. The LSG has higher risk-adjusted morbidity, readmission and reoperation/intervention rates compared to the LAGB, but lower reoperation/intervention rates compared to the LRYGB and ORYGB. There were no differences in mortality. Reduction in BMI and most of the weight-related comorbidities after the LSG also lies between those of the LAGB and the LRYGB/ORYGB. LSG has morbidity and effectiveness positioned between the LAGB and the LRYGB/ORYGB for data up to 1 year. As obesity is a lifelong disease, longer term comparative effectiveness data are most critical, and are yet to be determined.


Bone aerophones from Eynan-Mallaha (Israel) indicate imitation of raptor calls by the last hunter-gatherers in the Levant.
Direct evidence for Palaeolithic sound-making instruments is relatively rare, with only a few examples recorded from Upper Palaeolithic contexts, particularly in European cultures. However, theoretical considerations suggest that such artefacts have existed elsewhere in the world. Nevertheless, evidence for sound production is tenuous in the prehistoric archaeological record of the Levant, the study of music and its evolution being sparsely explored. Here we report new evidence for Palaeolithic sound-making instruments from the Levant with the discovery of seven aerophones made of perforated bird bones in the Final Natufian site of Eynan-Mallaha, Northern Israel. Through technological, use-wear, taphonomic, experimental and acoustical analyses, we demonstrate that these objects were intentionally manufactured more than 12,000 years ago to produce a range of sounds similar to raptor calls and whose purposes could be at the crossroads of communication, attracting hunting prey and music-making. Although similar aerophones are documented in later archaeological cultures, such artificial bird sounds were yet to be reported from Palaeolithic context. Therefore, the discovery from Eynan-Mallaha contributes new evidence for a distinctive sound-making instrument in the Palaeolithic. Through a combined multidisciplinary approach, our study provides important new data regarding the antiquity and development of the variety of sound-making instruments in the Palaeolithic at large and particularly at the dawn of the Neolithic in the Levant.


Lymphocyte-depletion Hodgkin's disease. Histopathologic diagnosis of marrow involvement.
Lymphocyte-depletion Hodgkin's disease (LDHD) is a rare and often misdiagnosed form of HD. Although marrow involvement is frequent in this disease, most pathologists are not familiar with the marrow lesion of LDHD, since the underlying disease is so unusual. In order to characterize the marrow lesion produced by LDHD, we reviewed biopsies or aspirates from the initial presentation of 22 patients meeting all the clinical and pathologic criteria for LDHD. These included 11 cases of the diffuse fibrosis subtype, eight cases of reticular subtype, and three cases not subclassified. Fifty-four percent of cases, primarily of the diffuse fibrosis subtype, had marrow involvement. Aspirations and biopsies were positive with essentially the same frequency. LDHD produces a characteristic consolidated lesion readily recognized on low-power examination and composed of amorphous, nonbirefringent eosinophilic background material, an inflammatory infiltrate, and Reed-Sternberg (RS) cells. Involvement may be focal and RS cells are generally scarce, requiring examination of multiple sections of well-fixed and stained material. Uninvolved marrow tends to be normocellular and frequently has increased numbers of eosinophils. The original diagnosis of LDHD often may be made from marrow examination alone. Early recognition of marrow involvement is important in facilitating prompt treatment and providing accurate staging without laparotomy.


Health Beliefs, Trust in Media Sources, Health Literacy, and Preventive Behaviors among High-Risk Chinese for COVID-19.
The coronavirus disease (COVID-19) broke out in China in January 2020 and has been effectively controlled in April 2020 after China's relentless efforts. People's engagement in disease-related preventive behaviors is crucial in containing such infectious disease. Vulnerable populations often have higher chances of developing severe illness from COVID-19 and the mortality rate is also higher. Thus, at-risk populations for COVID-19 request extra attention. The current study conducted a national online survey among vulnerable populations in China in early February 2020 to examine their engagement in coronavirus-related preventive health behaviors (e.g., frequent handwashing) and the potential determinants including factors from the Health Belief Model, trust in different media sources, and health literacy. The results suggested that the vulnerable populations' engagement in coronavirus-related preventive behaviors were significantly associated with barriers, benefits, self-efficacy, trust in doctors' social media, and trust in TV for COVID-19-related information. Besides, barriers, benefits, self-efficacy, trust in doctors' social media, and trust in TV mediated the effects of health literacy on preventive behaviors. Our findings provided directions for future health promotions and interventions targeting vulnerable populations to enhance their preventive behaviors in China.


Rational Design of Molecularly Imprinted Polymers Using Quaternary Ammonium Cations for Glyphosate Detection.
Molecularly imprinted polymers have emerged as cost-effective and rugged artificial selective sorbents for combination with different sensors. In this study, quaternary ammonium cations, as functional monomers, were systematically evaluated to design imprinted polymers for glyphosate as an important model compound for electrically charged and highly water-soluble chemical compounds. To this aim, a small pool of monomers were used including (3-acrylamidopropyl)trimethylammonium chloride, [2-(acryloyloxy)ethyl]trimethylammonium chloride, and diallyldimethylammonium chloride. The simultaneous interactions between three positively charged monomers and glyphosate were preliminary evaluated using statistical design of the experiment method. Afterwards, different polymers were synthesized at the gold surface of the quartz crystal microbalance sensor using optimized and not optimized glyphosate-monomers ratios. All synthesized polymers were characterized using atomic force microscopy, contact angle, Fourier-transform infrared, and X-ray photoelectron spectroscopy. Evaluated functional monomers showed promise as highly efficient functional monomers, when they are used together and at the optimized ratio, as predicted by the statistical method. Obtained results from the modified sensors were used to develop a simple model describing the binding characteristics at the surface of the different synthesized polymers. This model helps to develop new synthesis strategies for rational design of the highly selective imprinted polymers and to use as a sensing platform for water soluble and polar targets.


Mobilizing support for the extreme right: a discursive analysis of minority leadership.
This study uses a tripolar model of minority influence to investigate social category constructions of extreme right politicians. The analysis focuses on Geert Wilders, leader of the extreme right Party For Freedom (PVV) in the Netherlands. It is examined how this popular politician construes the interdependent relations between himself, the population, and mainstream politicians, and discursively manages his controversial standpoints and proposals. Four parliamentary debates are analysed. The analysis shows that by defining national identity, Wilders invokes a self-image as a prototypical member of the population. Furthermore, and in contrast to other politicians, Wilders works up a self-image of a responsible and realistic politician who is group oriented. In addition, the analysis suggests that being a minority can be of strategic political value and therefore a position to foster. The relevance of the analysis for social psychological approaches to leadership and political minorities is discussed.


Bicaudal-D1 regulates the intracellular sorting and signalling of neurotrophin receptors.
We have identified a new function for the dynein adaptor Bicaudal D homolog 1 (BICD1) by screening a siRNA library for genes affecting the dynamics of neurotrophin receptor-containing endosomes in motor neurons (MNs). Depleting BICD1 increased the intracellular accumulation of brain-derived neurotrophic factor (BDNF)-activated TrkB and p75 neurotrophin receptor (p75(NTR)) by disrupting the endosomal sorting, reducing lysosomal degradation and increasing the co-localisation of these neurotrophin receptors with retromer-associated sorting nexin 1. The resulting re-routing of active receptors increased their recycling to the plasma membrane and altered the repertoire of signalling-competent TrkB isoforms and p75(NTR) available for ligand binding on the neuronal surface. This resulted in attenuated, but more sustained, AKT activation in response to BDNF stimulation. These data, together with our observation that Bicd1 expression is restricted to the developing nervous system when neurotrophin receptor expression peaks, indicate that BICD1 regulates neurotrophin signalling by modulating the endosomal sorting of internalised ligand-activated receptors.


Evolutionary origin of the segmental duplication encompassing the wheat GLU-B1 locus encoding the overexpressed Bx7 (Bx7OE) high molecular weight glutenin subunit.
Sequencing of a BAC clone encompassing the Glu-B1 locus in Glenlea, revealed a 10.3 Kb segmental duplication including the Bx7 gene and flanking an LTR retroelement. To better understand the evolution of this locus, two collections of wheat were surveyed. The first consisted of 96 diploid and tetraploid species accessions while the second consisted of 316 Triticum aestivum cultivars and landraces from 41 countries. The genotypes were first characterized by SDS-PAGE and a total of 40 of the 316 T. aestivum accessions were found to display the overexpressed Bx7 phenotype (Bx7OE). Three lines from the 96 diploid/tetraploid collection also displayed the stronger intensity staining characteristic of the Bx7(OE) subunit. The relative amounts of the Bx7 subunit to total HMW-GS were quantified by RP-HPLC for all Bx7OE accessions and a number of checks. The entire collection was assessed for the presence of four DNA markers namely an 18 bp indel of the coding region of Bx7 variant alleles, a 43 bp indel of the 5'-region and the left and right junctions of the LTR retrotransposon borders and the duplicated segment. All 43 accessions found to have the Bx7OE subunit by SDS-PAGE and RP-HPLC produced the four diagnostic PCR amplicons. None of the lines without the Bx7OE had the LTR retroelement/duplication genomic structure. However, the 18 and 43 bp indel were found in accessions other than Bx7OE. These results indicate that the overexpression of the Bx7 HMW-GS is likely the result of a single event, i.e., a gene duplication at the Glu-B1 locus mediated by the insertion of a retroelement. Also, the 18 and 43 bp indels pre-date the duplication event. Allelic variants Bx7*, Bx7 with and without 43 bp insert and Bx7OE were found in both tetraploid and hexaploid collections and shared the same genomic organization. Though the possibility of introgression from T. aestivum to T. turgidum cannot be ruled out, the three structural genomic changes of the B-genome taken together support the hypothesis of multiple polyploidization events involving different tetraploid progenitors.


[Awareness of the issues of HIV infection in the dwellers of the Central Administrative District of Moscow].
To study the awareness of HIV infection in the dwellers of the Central Administrative District of Moscow. A continuous cross-sectional survey was made in all the citizens who applied to the V.A. Gilyarovsky Mental Hospital Three, Branch Four, for information on the day of the survey and gave their consent to participate in this survey that was performed in 4 steps; a total of 414 persons were questioned. Their knowledge and ideas were anonymously assessed using a specially developed questionnaire. After analyzing their replies, the respondents were divided into 3 groups: 1) representatives of the so-called general population; 2) draft-age youngsters; 3) health care workers. The draftees (34%) gave the largest number of wrong answers to the question whether human immunodeficiency virus (HIV) could be transmitted through mosquito bites (p=0.0001). Among the healthcare workers, 81% of the respondents indicated that HIV could not be transmitted through mosquito bites; the proportion of right answers among the general population was 64.3%. The statement that a condom reliably protects against HIV infection was considered to be true by 52.4% of the health care workers, 56% of the draftees, and 62.2% of the representatives of the general population. The HIV/AIDS topic was not relevant for 43.4% of the general population and 58.3% of the health care workers; 98.7% of the respondents of the general population pointed that blood should be sampled for testing for HIV antibodies to find out whether a person had HIV (AIDS); this answer was chosen by 87.5% of the surveyed health care workers. Low knowledge about HIV infection particularly among the draft-age youngsters is evidence for the insufficient efficiency of performed preventive measures among both the general population and the organized young people. Attention is drawn to the opinion of the respondent health care workers as to the reliability of using the condom to prevent HIV transmission. The findings will be kept in mind when elaborating the teaching programs.