Thalidomide down-regulates transcript levels of GC-rich promoter genes in multiple myeloma.
Thalidomide (Thd), a potent teratogen, was shown to have therapeutic potential in cancer, primarily in multiple myeloma (MM), yet its mechanism of action has not been elucidated. It was recently suggested that its teratogenicity is derived from interference in expression of genes regulated by GC-rich promoters by blocking the binding of SP1 transcription factor to its motif. We explored the validation of the proposed model by focusing on potential molecular targets associated with MM pathogenesis. Cell lines RPMI 8226, U266, and ARH-77 were exposed for 24 h to racemic Thd and analyzed for apoptosis, membranal expression of CD29 and CD63, transcript level of hTERT, CD63, and IGFI-R (characterized by GC-rich motifs) and telomerase activity. Analysis of an hTERT core promoter reporter gene expression [enhanced green fluorescent protein (EGFP)] in transiently transfected RPMI 8226 incubated with racemic and steric (+/-)-enantiomers of Thd was performed. A consistent reduction ( approximately 10-40%) in transcript levels of all three assayed genes in all three cell lines was demonstrated in the presence of racemic Thd. Significant reduction of EGFP was demonstrated in cells transfected with hTERT reporter gene and treated with racemic and (S)-Thd. Our results show that Thd's antimyeloma activity can be ascribed to the same mechanism responsible for its teratogenic effect and that the inhibition of GC-rich promoter genes is mostly attributed to the S-racemate. Indeed, this selectivity delineates GC-rich promoter genes as a unique group eligible for specific drug targeting.


Menaquinone as the Secondary Electron Acceptor in the Type I Homodimeric Photosynthetic Reaction Center of Heliobacterium modesticaldum.
The type I photosynthetic reaction center (RC) of heliobacteria (hRC) is a homodimer containing cofactors almost analogous to those in the plant photosystem I (PS I). However, its three-dimensional structure is not yet clear. PS I uses phylloquinone (PhyQ) as a secondary electron acceptor (A1), while the available evidence has suggested that menaquinone (MQ) in hRC has no function as A1. The present study identified a new transient electron spin-polarized electron paramagnetic resonance (ESP-EPR) signal, arising from the radical pair of the oxidized electron donor and the reduced electron acceptor (P800(+)MQ(-)), in the hRC core complex and membranes from Heliobacterium modesticaldum. The ESP signal could be detected at 5-20 K upon flash excitation only after prereduction of the iron-sulfur center, F(X), and was selectively lost by extraction of MQ with diethyl ether. MQ was suggested to be located closer to F(X) than PhyQ in PS I based on the simulation of the unique A/E (A, absorption; E, emission) ESP pattern, the reduction/oxidation rates of MQ, and the power saturation property of the static MQ(-) signal. The result revealed the quinone usage as the secondary electron acceptor in hRC, as in the case of PS I.


Head-to-Head Comparison of 2 Paclitaxel-Coated Balloons for Femoropopliteal Lesions.
There is a scarcity of published head-to-head comparisons between different paclitaxel-coated angioplasty balloons. More prospective safety data to support the health care economic reimbursement processes are needed. The aim of this study was to report the safety and efficacy of the Passeo-18 Lux drug-coated balloon (DCB) (Biotronik AG) for the treatment of symptomatic peripheral artery disease caused by stenosis, restenosis, or occlusion of the femoral and/or popliteal arteries. A total of 302 patients were randomized 1:1 and assigned to the Passeo-18 Lux DCB (study device) group or the IN.PACT Admiral DCB (control device, Medtronic Vascular) group for testing of noninferiority. The primary efficacy endpoint was freedom from clinically driven target lesion revascularization at 12 months. The primary safety endpoint was a composite of freedom from device-/procedure-related death through 30 days postindex procedure, major target limb amputation, and clinically driven target vessel revascularization at 12 months. At 12 months, 130 of 134 patients in the IN.PACT Admiral group had freedom from clinically driven target lesion revascularization (97.0%) compared with 137 of 141 patients in the Passeo-18 Lux group (97.2%). The primary safety endpoint showed 96.3% in the control group vs 95.7% in the study device group. The null hypothesis of inferiority on both efficacy and safety was rejected. The Kaplan-Meier estimate of primary patency at 1 year was 88.7% in the control arm vs 91.5% in the study device arm. The Passeo-18 Lux and the IN.PACT Admiral DCBs demonstrate comparable results with excellent effectiveness and safety through 12 months for femoropopliteal interventions.


Insulin therapy in neonatal diabetes mellitus: a review of the literature.
Neonatal diabetes mellitus (NDM) is a rare disorder, and guidance is limited regarding its optimal management. We reviewed insulin usage in NDM, with a focus on continuous subcutaneous insulin infusion (CSII). A PubMed search identified 40 reports of patients with NDM treated with insulin published between 1994 and 2016. Data concerning treatment of NDM are limited. CSII resolves some of the issues associated with insulin therapy in neonates. No clinical trials of CSII in NDM have been reported. Case reports suggest that CSII is a safe and effective means of treating NDM. CSII was initiated to improve glycaemic control, for practicality and convenience, and to overcome difficulties associated with the maintenance of long-term intravenous catheters. CSII can provide better glycaemic control than multiple daily injections, with few hypoglycaemic events. Continuous glucose monitoring integrated with the pump helps provide more precise control of blood glucose levels. CSII generally uses short-acting insulin or rapid-acting insulin analogues, and those that are approved for use in neonates appear to be appropriate for the treatment of NDM using an insulin pump. Information from case reports indicates that CSII is safe and effective for the management of NDM.


Computing 2D constrained delaunay triangulation using the GPU.
We propose the first graphics processing unit (GPU) solution to compute the 2D constrained Delaunay triangulation (CDT) of a planar straight line graph (PSLG) consisting of points and edges. There are many existing CPU algorithms to solve the CDT problem in computational geometry, yet there has been no prior approach to solve this problem efficiently using the parallel computing power of the GPU. For the special case of the CDT problem where the PSLG consists of just points, which is simply the normal Delaunay triangulation (DT) problem, a hybrid approach using the GPU together with the CPU to partially speed up the computation has already been presented in the literature. Our work, on the other hand, accelerates the entire computation on the GPU. Our implementation using the CUDA programming model on NVIDIA GPUs is numerically robust, and runs up to an order of magnitude faster than the best sequential implementations on the CPU. This result is reflected in our experiment with both randomly generated PSLGs and real-world GIS data having millions of points and edges.


Ambrisentan therapy in patients with pulmonary arterial hypertension who discontinued bosentan or sitaxsentan due to liver function test abnormalities.
Some endothelin receptor antagonists (ERAs) are associated with liver function test (LFT) result abnormalities. However, ambrisentan has an incidence of serum aminotransferase levels more than three times the upper limit of normal (ULN), similar to that observed in PAH patients who are not receiving ERAs. Because ambrisentan may provide benefits in PAH patients who have discontinued ERA therapy due to LFT abnormalities, we evaluated the safety and efficacy of ambrisentan in this patient population. Patients who previously discontinued bosentan and/or sitaxsentan due to LFT abnormalities received ambrisentan, 2.5 mg qd, for 4 weeks followed by 5 mg/d for 8 weeks. The primary end point was the incidence of aminotransferase levels more than three times ULN considered by the investigator to be related to ambrisentan and resulting in drug discontinuation. Secondary end points included aminotransferase levels more than five times ULN requiring drug discontinuation and more than three times ULN requiring dose reduction, as well as changes in 6-min walk distance (6MWD), Borg dyspnea index, World Health Organization functional class, and Short Form-36 health survey score. Patients continued treatment beyond the 12-week end point with monthly monitoring of LFTs. Thirty-six patients who previously discontinued bosentan (n = 31), sitaxsentan (n = 2), or both (n = 3) were enrolled. At baseline, 69.4% of patients were receiving prostanoid and/or sildenafil therapy. No patient had an aminotransferase level more than three times ULN that required ambrisentan discontinuation. One patient had a transient aminotransferase level more than three times ULN that resolved following a temporary dose reduction. No additional aminotransferase levels more than three times ULN were observed with long-term treatment (median exposure, 102 weeks), despite dose increases to 10 mg qd in more than half of the patients. Significant improvements in 6MWD and other efficacy assessments were observed. Ambrisentan treatment may be an option for patients who have discontinued bosentan and/or sitaxsentan therapy due to LFT result abnormalities. Clinicaltrials.gov Identifier NCT00423592.


The structure of adenovirus chromatin in infected cells.
The structure of adenovirus chromatin in infected cells was studied by micrococcal nuclease digestion and hybridization with virus-specific probes. In the early phase of infection (5 h) a significant proportion of viral molecules was organized like actively transcribed cellular chromatin. As expected for a transcriptionally active population of molecules, even at high multiplicity of infection the nucleosomal repeating pattern was less distinct than in a transformed cell which contained the corresponding but less active genomic region. The observed repeating pattern in infected cells was unlikely to be due to integrated molecules since less than 0.07% of input genomes became associated with cellular DNA. After the onset of viral DNA replication, the pool of viral chromatin organized like cellular chromatin rapidly increased. In addition, newly replicated molecules also maintained the cellular chromatin-like organization as measured by [3H]thymidine incorporation after the cessation of cellular DNA synthesis. These data suggest that newly replicated viral molecules are organized by histones into cell-like chromatin throughout the infection cycle. Coincident with the peak of viral DNA and core protein synthesis, and the decline of histone synthesis, the late, core-like non-repeating viral chromatin became dominant, increasingly obscuring the underlying repeating pattern. Experiments suggest that this late chromatin is destined for encapsidation, that the early chromatin persists and that viral core proteins do not displace histones on viral DNA. A model is proposed suggesting that transcription and type I replication occur on histone-condensed templates, while type II replication products late in infection are condensed by core proteins and are destined for encapsidation.


Chlamydia trachomatis secretion of hypothetical protein CT622 into host cell cytoplasm via a secretion pathway that can be inhibited by the type III secretion system inhibitor compound 1.
Using antibodies raised with C. trachomatis fusion proteins, we localized a hypothetical protein encoded by the ORF ct622 in the cytoplasm of C. trachomatis-infected mammalian cells. The detection was specific since the antibody labelling of CT622 protein was removed by preabsorption with CT622 but not other fusion proteins. We similarly confirmed that CT621, a known secretion protein encoded by a hypothetical ORF downstream of ct622, was secreted into host cell cytosol. Proteins CT622 and CT621 displayed a similar secretion pattern, with both intra-inclusion and host cell cytosol localization, that was distinct from that of CPAF (chlamydial protease/proteasome-like activity factor). However, the expression and secretion kinetics differed significantly between CT622 and CT621: CT622 mRNA was detected at 2 h, protein at 6 h and secretion of protein into host cell cytoplasm at 36 h post-infection, while CT621 mRNA was detected at 8 h, protein at 16 h and secretion at 24 h. The secretion of both CT622 and CT621 was blocked by N'-(3,5-dibromo-2-hydroxybenzylidene)-4-nitrobenzohydrazide (compound 1), an inhibitor known to target the type III secretion system of bacteria. These results suggest that CT621 and CT622 may fulfil different functions during chlamydial intracellular growth. Further characterization of these proteins may generate important information for understanding chlamydial pathogenesis.


Dry and wet interfaces: influence of solvent particles on molecular recognition.
We present a coarse-grained lattice model to study the influence of water on the recognition process of two rigid proteins. The basic model is formulated in terms of the hydrophobic effect. We then investigate several modifications of our basic model showing that the selectivity of the recognition process can be enhanced by considering the explicit influence of single solvent particles. When the number of cavities at the interface of a protein-protein complex is fixed as an intrinsic geometric constraint, there typically exists a characteristic fraction that should be filled with water molecules such that the selectivity exhibits a maximum. In addition, the optimum fraction depends on the hydrophobicity of the interface so that one has to distinguish between dry and wet interfaces.


Overt attention toward oriented objects in free-viewing barn owls.
Visual saliency based on orientation contrast is a perceptual product attributed to the functional organization of the mammalian brain. We examined this visual phenomenon in barn owls by mounting a wireless video microcamera on the owls' heads and confronting them with visual scenes that contained one differently oriented target among similarly oriented distracters. Without being confined by any particular task, the owls looked significantly longer, more often, and earlier at the target, thus exhibiting visual search strategies so far demonstrated in similar conditions only in primates. Given the considerable differences in phylogeny and the structure of visual pathways between owls and humans, these findings suggest that orientation saliency has computational optimality in a wide variety of ecological contexts, and thus constitutes a universal building block for efficient visual information processing in general.


[Damage to the liver DNA of rats during the endogenous synthesis of N-nitrosodimethylamine].
The damage of liver DNA formation during endogenic synthesis of N-nitrosodimethylamine (NDMA) have been studied after introduction of its precursors, dimethylamine, amidopyrine and sodium nitrite, into the rat stomach. A combined administration of various doses of dimethylamine and nitrite increased the amount of single-strand DNA from 3.0 to 11.3%. The maximum DNA damage after administration of the precursors was observed after 24 h, and after 48 h it decreased to the control level. Pretreatment of rats with dimethylamine or nitrite increased the DNA damage induced by NDMA formation (37.4% and 41.6%, respectively).


EFFECT OF BIOTIN ON FATTY ACID DISTRIBUTION IN ESCHERICHIA COLI.
Gavin, John J. (Rutgers, The State University, New Brunswick, N.J.), and Wayne W. Umbreit. Effect of biotin on fatty acid distribution in Escherichia coli. J. Bacteriol. 89:437-443. 1965.-Biotin deficiency causes changes in the composition and distribution of the fatty acids in cell wall-cell membrane fractions of Escherichia coli T 94A. Most notable among the fatty acid changes are decreased amounts of unsaturated fatty acids, the presence of unsaponifiable lipid material, and the lack of a lipopolysaccharide fraction in the cell wall-cell membrane. Also, though the hexane-extractable material from the lipoprotein fraction of biotin-adequate cells will transfer glucose from water to hexane, the same material from biotin-deficient cells will not.


Hydrothermal synthesis of Bi2WO6 with a new tungsten source and enhanced photocatalytic activity of Bi2WO6 hybridized with C3N4.
Bi2WO6 nanosheets were synthesized by a hydrothermal method with H2WO4 for the first time. The band structure of Bi2WO6 was investigated on the basis of density functional theory calculations. Bi2WO6 photocatalysts showed photocatalytic activity for the degradation of methylene blue under visible light irradiation. Kinetic studies using radical scavenger technologies suggested that holes were the dominant photo-oxidants. After hybridization with C3N4, the photocatalytic activity of Bi2WO6 was obviously enhanced. The enhanced photocatalytic activity of the C3N4/Bi2WO6 photocatalysts could be attributed to the effective separation of photogenerated e-/h+ pairs. The photogenerated holes on the valence band of Bi2WO6 can transfer to the highest occupied molecular orbital of C3N4via the well-developed interface, causing a reduction in the probability of e-/h+ recombination; consequently, large numbers of photogenerated holes led to the enhancement of the photocatalytic activity.


[Effect of distraction by various forces on the elbow joint in rabbits].
The elbow joints of 115 adult live rabbits have been subjected to experimental distraction by various forces and for different intervals. The forces applied were one tenth and one half, respectively, of the mean body weights; thus, a calculated reduction of one eleventh and five elevenths, respectively, of the force transmitted through the articulating joint surfaces was achieved. The distraction was performed for periods of 1, 2, 4 and 8 weeks. The forces were administered by means of an extraarticular device which allowed motion of the joints. Controls had been provided for to prove the noneffectiveness of the distraction device per se to the joint structures under study. Both upper limbs--one side always served as control--were subjected to radiological, histological/histochemical, angiographic and cytological examination; cartilage in addition was treated by vital staining or, alternatively, by producing splitting lines. The results were as follows: (1) Extensive local and more generalized hyperemia involving the whole limb in question was produced regardless of strength and duration of distraction. (2) Under all experimental conditions subsynovial hemorrhage and hemarthrosis developed. (3) Subsynovial hemorrhage caused the development of granulomatous and, subsequently, fibrous synovitis with simultaneously demonstrable hemosiderin depots. (4) Hemarthrosis was persistent during the entire period of observation. (5) Articular cartilage revealed moderate signs of degeneration and also irregularities of the usual pattern of splitting lines after continuous distraction for 8 weeks. At the same time, subchondral bone atrophy appeared. Vital staining revealed increased cartilage staining under mild distraction; moderate and marked distraction caused definitively less staining. Subsynovial hemorrhage and hemarthrosis are explained as partial vacuum effects. Concerning the moderate cartilage changes, a multifactorial genesis is presumed; the possible role of chemical, nutritional and mechanical factors is discussed. The widespread hyperemia most likely is caused by mechanical stimulation going along with joint distraction; capsular hyperemia might be a phenomenon immediately related to synovitis. Finally, the experimental results are discussed relative to observations made during clinical traction therapy.


[The origin of the eukaryotic cell. IV. The general hypothesis of the autogenous origin of eukaryotes].
The general hypothesis of autogenous (non-symbiotic) origin of the eukaryotic cell summarises some hypotheses explaining possible ways of the origin of main components and organelles of such a cell (the primary unicellular protist). Six hypothesises are suggested. Arising of the eukaryotic surface membrane of protist (cell) as a result of modification of its lipidoacidic composition, when most of synblocks and ensembles of eukaryotic enzymes sink into the cytoplasm (due to membrane vesiculation). Establishment of eukaryotic cytoplasm on the basis of successive formation of two locomotory-supporting apparates: the primary one (microtrabecular system), and the second one (cytoskeleton). Arising of the nucleus from a polyheteronomous nucleoid of proeukaryotes. A combinatorical hypothesis of mitosis formation. Polyheteronucleoid hypothesis of the origin of the mitochondria and chloroplasts. Arising of the flagellum from the contractile tentacle-like organelle, whose axoneme is made of single microtubules. A close interrelation and interaction in the process of evolution is noted between surface membranes, the cytoplasm and the nucleus. In accord a principles of block-construction and heterochrony (see: Seravin, 1986r), the author explains the preservation of prokaryotic signs of organization in some components (and organelles) of eukaryotic cell (and protists).


Activity, adiposity and weight change in Jamaican adults.
Populations in developing countries are particularly vulnerable to the development of obesity in the period of rapid transition to a more modernized lifestyle. We sought to determine the relationship between activity energy expenditure (AEE), adiposity and weight change in an adult population undergoing rapid socio-economic transition. Total daily energy expenditure (TDEE) was measured using the doubly labelled water method, resting energy expenditure (REE) using indirect calorimetry and AEE calculated as the difference between TDEE and REE, in adults from a working class community in Spanish Town, Jamaica. During six years of follow-up, weight was measured between one and four times. Mixed effects regression modelling was used to test for association between components of the energy budget and weight change. Men (n = 17) weighed more but women (n = 18), had significantly more body fat, 38.5% vs 24.5%, respectively (p < 0.01). Men had higher levels of EE, particularly AEE after adjustment for body weight, 66.3 versus 46.4 kJ/kg.d for men and women, respectively (p < 0.001). At baseline, adjusted AEE was inversely associated with body fat in men and women, r = -0.46 and r = -0.48, respectively (p < 0.05). Mean rate of weight change was + 1.1 and + 1.2 kg/year for men and women, respectively. No component of EE, ie TDEE, REE or AEE, significantly predicted weight change in this small sample. These results suggest an important role for AEE in maintaining low levels of adiposity. The lack of association between EE and weight change, however, suggests populations in transition are at risk of obesity from environmental factors (eg dietary) other than simply declining physical activity levels.


[Scientific Department of Gerontological Nursing of the Brazilian Nursing Association].
This paper aimed to consider the creation of the Scientific Department of Gerontological Nursing within the Brazilian Nursing Association, considering the context of population ageing, and the development and consolidation of this specialty in the country. In the reflexive process, it was possible to rely on the historical analysis of the revised literature and authors' reports. The results showed the movement of nurses, in recent decades, to the production of knowledge, as well as their incorporation by the entity, and the commitment of its members to achieve the goals proposed to the Scientific Department of Gerontological Nursing. It is concluded that its creation represents a milestone to the scientific and political organization of the nursing professionals who seek to qualify themselves for an autonomous and competent care of the elderly and their families.


Door-to-needle times in patients treated by on-site and off-site on-call neurologists. PRISA study.
Hospital on-call neurology shifts are frequently on-site, but some on-call services may be off-site or mixed. Intravenous tissue plasminogen activator (tPA) is one of the main reperfusion treatments for acute ischaemic stroke (AIS). This study assesses door-to-needle times (DNT) when the neurologist is on-site or off-site. We performed a prospective, observational study from 2012 to 2017, including patients with AIS and treated with tPA. Data were collected on sex, age, door-to-scan time, scan-to-needle time, and DNT. The on-duty neurologist was on-site from 08:00 to 20:00, and on call but off-site from 20:00 to 8:00. Three groups were formed: on-site, off-site, and off-site with resident present. Our sample included 138 patients. The mean age was 69.7 years, and 45.7% of patients were women. Ninety-six patients were admitted during the on-site shift, 25 during the off-site shift, and 17 during the off-site-resident present shift. Patients admitted during the on-site and off-site shifts presented DNTs of 59 and 72 minutes, respectively (P = .003). DNTs were 59, 74, and 68 minutes (P = .001), respectively, for the on-site, off-site, and off-site-resident present shifts; the difference between DNTs for on-site and off-site shifts was statistically significant. No differences were observed between DNTs according to time of day (morning, afternoon, or night), or between weekdays and weekends. DNT is influenced by whether the on-duty neurologist is on- or off-site at the time of code stroke activation. The presence of a neurology resident can reduce DNT.


Temporal dynamic of parasite-mediated linkages between the forest canopy and soil processes and the microbial community.
Parasitic plants are important drivers of community and ecosystem properties. In this study, we identify different mechanisms by which mistletoe (Viscum album subsp. austriacum) can affect soil chemical and biological properties at different temporal stages of parasitism. We quantified the effect of parasitism on host growth and the number of frugivorous mutualists visiting the host canopy. Then we collected, identified, and weighed the organic matter input underneath tree canopies and analyzed its nutrient content. Simultaneously, we analyzed soil samples under tree canopies and examined the chemical properties, microbial abundance, and functional evenness of heterotrophic microbial communities. Mistletoe increased the amount, quality, and diversity of organic matter input beneath the host canopy, directly through its nutrient-rich litter and indirectly through a reduction in host litterfall and an increase in bird-derived debris. All these effects gave rise to enriched hotspots able to support larger and more functionally even soil microbial communities beneath parasitized hosts, the effects of which were accentuated after host death. We conclude that mistletoe, together with the biotic interactions it mediates, plays a key role in intensifying soil resource availability, regulating the functional evenness, abundance, and spatial distribution of soil microbial communities.


Pancytopenia: a rare complication of Graves' disease.
A 27-year-old male patient who presented to the emergency room with complaints of sweating, palpitations, heat intolerance, insomnia and weight loss for the last 3 months. His medical history was significant for hypertension. On examination, he was tachycardic, hypertensive, had tremors of the upper extremities and a smooth goitre with a thyroid bruit. Laboratory assessment revealed a suppressed thyroid-stimulating hormone, high free thyroxine and positive thyroid receptor antibodies. Complete blood count showed pancytopenia. As part of the work-up for pancytopenia, haptoglobin, ferritin, Coombs test, reticulocyte count hepatitis B and C antibodies were done, all of which were normal. Patient was started on methimazole, propranolol and hydrocortisone. His symptoms improved through the hospital course and he was subsequently discharged. Thyroidectomy was done once the patient's hyperthyroidism was controlled. Levothyroxine was started for the control of postsurgical hypothyroidism. Six months after thyroidectomy, the patient was euthyroid and the pancytopenia resolved.


Helicobacter pylori induces cell migration and invasion through casein kinase 2 in gastric epithelial cells.
Chronic infection with Helicobacter pylori (H. pylori) is causally linked with gastric carcinogenesis. Virulent H. pylori strains deliver bacterial CagA into gastric epithelial cells. Induction of high motility and an elongated phenotype is considered to be CagA-dependent process. Casein kinase 2 plays a critical role in carcinogenesis through signaling pathways related to the epithelial mesenchymal transition. This study was aimed to investigate the effect of H. pylori infection on the casein kinase 2-mediated migration and invasion in gastric epithelial cells. AGS or MKN28 cells as human gastric epithelial cells and H. pylori strains Hp60190 (ATCC 49503, CagA(+)) and Hp8822 (CagA(-)) were used. Cells were infected with H. pylori at multiplicity of infection of 100 : 1 for various times. We measured in vitro kinase assay to examine casein kinase 2 activity and performed immunofluorescent staining to observe E-cadherin complex. We also examined β-catenin transactivation through promoter assay and MMP7 expression by real-time PCR and ELISA. H. pylori upregulates casein kinase 2 activity and inhibition of casein kinase 2 in H. pylori-infected cells profoundly suppressed cell invasiveness and motility. We confirmed that casein kinase 2 mediates membranous α-catenin depletion through dissociation of the α-/β-catenin complex in H. pylori-infected cells. We also found that H. pylori induces β-catenin nuclear translocation and increases MMP7 expressions mediated through casein kinase 2. We show for the first time that CagA(+) H. pylori upregulates cellular invasiveness and motility through casein kinase 2. The demonstration of a mechanistic interplay between H. pylori and casein kinase 2 provides important insights into the role of CagA(+) H. pylori in the gastric cancer invasion and metastasis.


Entomopathogenic nematodes as a model system for advancing the frontiers of ecology.
Entomopathogenic nematodes (EPNs) in the families Heterorhabditidae and Steinernematidae have a mutualistic-symbiotic association with enteric γ-Proteobacteria (Steinernema-Xenorhabdus and Heterorhabditis-Photorhabdus), which confer high virulence against insects. EPNs have been studied intensively because of their role as a natural mortality factor for soil-dwelling arthropods and their potential as biological control agents for belowground insect pests. For many decades, research on EPNs focused on the taxonomy, phylogeny, biogeography, genetics, physiology, biochemistry and ecology, as well as commercial production and application technologies. More recently, EPNs and their bacterial symbionts are being viewed as a model system for advancing research in other disciplines such as soil ecology, symbiosis and evolutionary biology. Integration of existing information, particularly the accumulating information on their biology, into increasingly detailed population models is critical to improving our ability to exploit and manage EPNs as a biological control agent and to understand ecological processes in a changing world. Here, we summarize some recent advances in phylogeny, systematics, biogeography, community ecology and population dynamics models of EPNs, and describe how this research is advancing frontiers in ecology.


Eplerenone is not superior to older and less expensive aldosterone antagonists.
Eplerenone is publicized to be extremely effective in reducing mortality from heart failure, with a reasonable side-effect profile. However, it is much more expensive compared with older aldosterone antagonists. We reviewed available evidence to assess whether increased expense was justified with outcomes data. The authors searched the PubMed, CENTRAL, CINAHL, and EMBASE databases for randomized controlled trials from 1966 through July 2011. Interventions included aldosterone antagonists (Aldactone [Pfizer, NY, NY], canrenone, eplerenone) in systolic heart failure. The comparator included standard medical therapy or placebo, or both. Outcomes assessed were mortality in the intervention versus the comparator groups, and rates of adverse events at the end of at least 8 weeks of follow-up. Event rates were compared using a forest plot of relative risk (RR) (95% confidence interval [CI]) using a random-effects model (Mantel-Haenszel) between the aldosterone antagonists and controls. We included 13 studies for aldosterone antagonists other than eplerenone, and 3 studies for eplerenone. There was significant reduction of mortality with all aldosterone antagonists, but eplerenone (15% mortality relative reduction; RR 0.85; 95% CI, 0.77-0.93; P=.0007) was outperformed by other aldosterone antagonists, namely, spironolactone and canrenone (26% mortality relative reduction; RR 0.74; 95% CI, 0.66-0.83; P <.0001). Reduction in cardiovascular mortality with eplerenone was 17% (RR 0.83; 95% CI, 0.75-0.92; P=.0005), while that with other aldosterone antagonists was 25% (RR 0.75; 95% CI, 0.67-0.84, P <.0001), without contributing significantly to an improved side-effect profile. Eplerenone does not appear to be more effective in reducing clinical events compared with older, less expensive aldosterone antagonists.


Lactobacillus rhamnosus septicaemia in a patient with a graft in the inferior vena cava.
A case of septicaemia that repeatedly showed growth of Lactobacillus rhamnosus in blood cultures is reported. The patient improved after removal of a Goretex patch in the inferior vena cava that was the focus of the infection. Lactobacilli can, in certain settings, be the cause of clinically important infections.


Protective Effect of Silibinin on Learning and Memory Impairment in LPS-Treated Rats via ROS-BDNF-TrkB Pathway.
Silibinin, a flavonoid derived from the herb milk thistle (Silybum marianum), has been used as a hepato-protectant in the clinical treatment of liver disease. In the present study, the effect of silibinin on lipopolysaccharide (LPS)-induced neuroinflammatory impairment in rats is investigated. Injection of LPS into lateral ventricle caused learning and memory impairment. Rats were treated with silibinin to see the effect in comparison with resveratrol as a positive control. Y-maze and Morris water maze tests showed that silibinin significantly attenuated memory damage caused by LPS treatment. At the molecular analysis, the levels of IL-1β and of IL-4 in the hippocampus were decreased and enhanced, respectively, by the treatment with silibinin. NF-κB expression was attenuated by silibinin treatment. Furthermore, generation of total reactive oxygen species (ROS) in the hippocampus was elevated in silibinin-treated groups, and so were the expressions of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB). At the same time, LPS-induced reduction of neurons in hippocampus was reversed by silibinin. In conclusion, silibinin ameliorated the impairment of learning and memory of LPS-injection rats, possibly due to the activation of ROS-BDNF-TrkB pathway in the hippocampus as well as the suppression of inflammatory response. This study gives an insight on the beneficial consequences of ROS in central nervous system. Silibinin might be a potential candidate drug for neurodegenerative diseases.


Pharmacodynamics and onset of action of esmolol in anesthetized dogs.
The pharmacodynamics and onset of action of esmolol, a novel, cardioselective beta adrenergic receptor antagonist with an ultra short duration of action, were studied in anesthetized dogs. Steady-state levels of beta blockade were attained within 10 min after initiation of esmolol infusion or when changing infusion rates. Similarly, steady-state blood levels of esmolol were attained within 30 min (the earliest sampling point) after starting an infusion and new steady-state blood levels were re-established again within 30 min after changing the infusion rates. Rapid recovery from beta blockade after termination of the esmolol infusion was paralleled by a rapid decline in blood levels of esmolol. The duration of action and elimination half-life both averaged less than 15 min. Excellent linear correlations were obtained between dose and steady-state blood concentration and the logarithm of the steady-state blood concentration and percentage of beta blockade. In a separate study, the onset of beta blockade with esmolol was observed within 15 sec of initiating a 60-sec infusion of 500 micrograms/kg/min. Peak beta blockade occurred at 30 to 45 sec after switching to a maintenance dose of 12.5, 25 or 50 micrograms/kg/min. The duration of peak effect was dependent on the maintenance dose. Peak blood levels of esmolol occurred immediately after stopping the loading dose and decreased to steady-state blood levels at 20 and 10 min after maintenance doses of 25 and 50 micrograms/kg/min, respectively. The results of these studies indicate that the onset, time to steady state and termination of beta blockade with esmolol are rapid and that an excellent correlation exists between the blood level of the drug and degree of beta blockade both during and after an esmolol infusion.


Mitral valve prolapse and coronary artery disease. Clinical, hemodynamic, and angiographic correlations.
Among 95 patients with angina pectoris and angiographically documented coronary artery disease (CAD), prolapse of the scallops of the posterior leaflet of the mitral valve (PLMV) was noted in 30 patients. Left ventriculograms in the right anterior oblique (RAO) projection revealed isolated prolapse of the posteromedial commissural scallop (PMCS) in 12 patients and the anterolateral commissural scallop (ALCS) in two patients. Seven patients had prolapse of both PMCS and ALCS, three had prolapse of the PMCS and middle scallop (MS), and six had prolapse of all three scallops of the PLMV. Left ventricular dilatation with increase trabeculations was observed in 19 patients. Contractility determined in a quantitative fashion by segmental motion analysis was markedly impaired in 29 patients. None of the patients had angiographic evidence of mitral insufficiency. Left ventricular dysfunction was documented in 28 patients by either elevated left ventricular end-diastolic pressure (LVEDP), low cardiac index (CI) or decreased ejection fraction (EF). In two patients in whom left ventricular contractility improved after aortocoronary by pass, previously prolapsed scallops could not be identified in the postoperative ventriculogram. Prolapsed PLMV is a frequent angiographic finding in patients with angiographically observed CAD. Impaired contractility of the ventricular myocardium and papillary muscles, left ventricular dilatation, and hypertrophy appear to play a significant role in the pathogenesis of this abnormality through distortion of the directional axis of the papillary muscles, asynergic contraction of the related free wall of the left ventricle, and changes in the normal spatial alignment necessary for mitral valve closure. The syndrome of papillary muscle dysfunction in patients with coronary artery disease represents a wider clinical spectrom than previously described.


Growth Characteristics of Bacillus cereus in Sake and during Its Manufacture.
Sake (Japanese rice wine) has been recognized as being low risk in terms of its microbiological safety. However, a confirmation of the food safety aspects of sake based on scientific evidence is important for establishing consumer confidence, in part because consumer concerns regarding food safety have increased. The presence of Bacillus cereus spores in refined rice wine has been reported, and in light of consumers' growing concern over food safety, the establishment of food and beverage safety is important for consumers' reassurance. Herein, to confirm the microbiological safety of sake, we investigated the content and growth of B. cereus. We conducted a spore addition test to determine whether B. cereus spores grow during sake production, and we observed no growth or germination of B. cereus spores during the manufacturing process. We also observed that processes such as solid-liquid separation and filtration help remove the risk posed by B. cereus. We then conducted a survey to assess the density of B. cereus in various commercial sake products. We analyzed 162 samples of commercial sake and observed that 11 of the products had ≥1 CFU of living cells in 1 mL of sake (detection rate, 6.8%). There was no product in which ≥100 CFU of living cells per 1 mL of sake was detected. Our findings confirmed that the density of these bacteria in sake is lower than that in other foods and that the probability of infection is very low. The emetic toxin produced by B. cereus was not detected in any of the sake samples. This is the first study based on experimental data demonstrating that B. cereus is not able to grow in sake or during the sake manufacturing process. We, thus, conclude that the safety risk of B. cereus in sake is negligible. Our findings indicating that B. cereus is not a significant hazard in the sake brewing process will contribute to food hygiene management based on scientific evidence in sake breweries.


Outer membrane protein P of Pseudomonas aeruginosa: regulation by phosphate deficiency and formation of small anion-specific channels in lipid bilayer membranes.
A new major outer membrane protein, P, was induced in Pseudomonas aeruginosa PAO1 upon growth in medium containing 0.2 mM or less inorganic phosphate. Studies with media containing different levels of phosphate and with mutants of PAO1 suggested that protein P was coregulated with alkaline phosphatase and phospholipase C. Protein P was substantially purified and shown to form sodium dodecyl sulfate-resistant oligomers on polyacrylamide gels. The incorporation of purified protein P into artificial lipid bilayers resulted in an increase of the membrane conductance by many orders of magnitude. Single-channel experiments demonstrated that protein P channels were substantially smaller than all previously studied porins from P. aeruginosa and enteric bacteria, with an average single-channel conductance in 1 M NaCl of 0.25 nS. The protein P channel was apparently not voltage induced or regulated. The results of single-channel conductance experiments, using a variety of different salts, allowed a minimum channel diameter estimate of 0.7 nm. Furthermore, from these results it was concluded that the protein P channel was highly specific for anions. Zero-current potential measurements confirmed that protein P was at least 30-fold more permeable for Cl- than for K+ ions. The possible biological role of the small, anion-specific protein P channels in phosphate uptake from the medium is discussed.


Prevalence of conditions potentially associated with lower urinary tract symptoms in men.
To estimate the frequency of conditions associated with lower urinary tract symptoms (LUTS, typically included when assessing benign prostatic hyperplasia, BPH), as other causes of LUTS should be excluded when diagnosing BPH, using data from the Olmsted County Study of Urinary Symptoms and Health Status among Men. During 1989-91, Caucasian men aged 40-79 years were randomly selected from the Olmsted County population. Before contact, eligibility was determined by reviewing the community medical records. Baseline exclusion criteria included comorbid pre-existing conditions or treatments, e.g. prostate, bladder or lower back surgery, bladder neck contracture or cancer, diabetes with lower extremity amputation, and neurological diseases, including Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, tabes dorsalis and stroke. Men with these conditions were excluded from the Olmsted County Study at baseline, because these conditions are potentially associated with LUTS. Of the 5100 randomly sampled men, 13.4% met at least one of the pre-existing exclusion criteria. Individually, the frequency of exclusions was 7.8% for prostate cancer or surgery, 4.8% for back surgery, 1.3% for bladder surgery and 1.4% for neurological conditions. All other conditions represented <1.0% of the study exclusions. Older men were more likely to meet at least one of the exclusion criteria, with men in their fifth to eighth decade having a total exclusion frequency of 1.4%, 5.4%, 8.5% and 32.8%, respectively. The most common reason for men in their fifth decade to be excluded was lower back surgery (0.9%), whereas the most common reason in the eighth was prostate surgery (21.8%). In men, conditions that may contribute to LUTS, other than BPH, are prevalent in the community and increase in frequency with age. It is important that other conditions associated with LUTS be excluded before a definitive diagnosis of BPH. Any oversight in this initial evaluation can potentially result in misclassification bias, misdiagnosis and incorrect treatment of patients.


An evaluation of operative outcome in patients with funnel chest diagnosed by means of the computed tomogram.
A questionnaire survey of 66 patients with funnel chest who underwent corrective surgical procedures by the sternal elevation method, with or without the application of metal strut, demonstrated that the operative result was good in 60.6% and fair in 39.4%. None of the patients rated the result as unsatisfactory. A computed tomogram of the chest wall was performed to study the depression (b/c), asymmetry (b'/b), and flatness (a/b) of the chest wall, where a was the maximum transverse distance of the chest wall, b and b' were the maximum distance from the anterior to the posterior chest wall at the left and right sides (b greater than b'), and c was the perpendicular distance from the point of the anterior chest wall at its greatest deformity to the level of the anterior tip of the spine. In patients with a good result, b/c and b'/b were well corrected, while in patients with a fair postoperative result, they were still significantly different from those in subjects with normal chest walls. Moreover, 85.7% of the patients (6/7) with b/c over 3.0 before operation had a fair postoperative result. The degree of a/b was not corrected in patients with either good or fair postoperative results. We conclude that an operative approach to lengthen ribs would be necessary to improve the degree of a/b, that in patients with severely depressed funnel chest, expressed as a b/c value over 3.0 by computed tomography, a transient support with struts should be applied, and finally, that a more careful approach for correction of asymmetry should be undertaken to improve the operative results.


Acetylcholine Protects against Candida albicans Infection by Inhibiting Biofilm Formation and Promoting Hemocyte Function in a Galleria mellonella Infection Model.
Both neuronal acetylcholine and nonneuronal acetylcholine have been demonstrated to modulate inflammatory responses. Studies investigating the role of acetylcholine in the pathogenesis of bacterial infections have revealed contradictory findings with regard to disease outcome. At present, the role of acetylcholine in the pathogenesis of fungal infections is unknown. Therefore, the aim of this study was to determine whether acetylcholine plays a role in fungal biofilm formation and the pathogenesis of Candida albicans infection. The effect of acetylcholine on C. albicans biofilm formation and metabolism in vitro was assessed using a crystal violet assay and phenotypic microarray analysis. Its effect on the outcome of a C. albicans infection, fungal burden, and biofilm formation were investigated in vivo using a Galleria mellonella infection model. In addition, its effect on modulation of host immunity to C. albicans infection was also determined in vivo using hemocyte counts, cytospin analysis, larval histology, lysozyme assays, hemolytic assays, and real-time PCR. Acetylcholine was shown to have the ability to inhibit C. albicans biofilm formation in vitro and in vivo. In addition, acetylcholine protected G. mellonella larvae from C. albicans infection mortality. The in vivo protection occurred through acetylcholine enhancing the function of hemocytes while at the same time inhibiting C. albicans biofilm formation. Furthermore, acetylcholine also inhibited inflammation-induced damage to internal organs. This is the first demonstration of a role for acetylcholine in protection against fungal infections, in addition to being the first report that this molecule can inhibit C. albicans biofilm formation. Therefore, acetylcholine has the capacity to modulate complex host-fungal interactions and plays a role in dictating the pathogenesis of fungal infections.


Topochemical Design of Cellulose-Based Carriers for Immobilization of Endoxylanase.
Xylooligosaccharides (XOSs) gained much attention for their use in food and animal feed, attributed to their prebiotic function. These short-chained carbohydrates can be enzymatically produced from xylan, one of the most prevalent forms of hemicellulose. In this work, endo-1,4-β-xylanase from Thermotoga maritima was immobilized on cellulose-based beads with the goal of producing xylooligosaccharides with degrees of polymerization (DPs) in the range of 4-6 monomeric units. More specifically, the impact of different spacer arms, tethers connecting the enzyme with the particle, on the expressed enzymatic activity and oligosaccharide yield was investigated. After surface functionalization of the cellulose beads, the presence of amines was confirmed with time of flight secondary ion mass spectrometry (TOF-SIMS), and the influence of different spacer arms on xylanase activity was established. Furthermore, XOSs (DPs 2-6) with up to 58.27 mg/g xylan were obtained, which were greatly enriched in longer oligosaccharides. Approximately 80% of these XOSs displayed DPs between 4 and 6. These findings highlight the importance of topochemical engineering of carriers to influence enzyme activity, and the work puts forward an enzymatic system focusing on the production of longer xylooligosaccharides.


Biofabrication of osteochondral tissue equivalents by printing topologically defined, cell-laden hydrogel scaffolds.
Osteochondral defects are prone to induce osteoarthritic degenerative changes. Many tissue-engineering approaches that aim to generate osteochondral implants suffer from poor tissue formation and compromised integration. This illustrates the need for further improvement of heterogeneous tissue constructs. Engineering of these structures is expected to profit from strategies addressing the complexity of tissue organization and the simultaneous use of multiple cell types. Moreover, this enables the investigation of the effects of three-dimensional (3D) organization and architecture on tissue function. In the present study, we characterize the use of a 3D fiber deposition (3DF) technique for the fabrication of cell-laden, heterogeneous hydrogel constructs for potential use as osteochondral grafts. Changing fiber spacing or angle of fiber deposition yielded scaffolds of varying porosity and elastic modulus. We encapsulated and printed fluorescently labeled human chondrocytes and osteogenic progenitors in alginate hydrogel yielding scaffolds of 1×2 cm with different parts for both cell types. Cell viability remained high throughout the printing process, and cells remained in their compartment of the printed scaffold for the whole culture period. Moreover, distinctive tissue formation was observed, both in vitro after 3 weeks and in vivo (6 weeks subcutaneously in immunodeficient mice), at different locations within one construct. These results demonstrate the possibility of manufacturing viable centimeter-scaled structured tissues by the 3DF technique, which could potentially be used for the repair of osteochondral defects.


Distribution and kinetics of membrane dielectric polarization. II. Frequency domain studies of gating currents.
We have studied the admittance of the membrane of squid giant axon under voltage clamp in the absence of ionic conductances in the range of 0-12 kHz for membrane potentials (V) between --130 and 70 mV. The admittance was measured at various holding potentials (HP) or 155 ms after pulsing from a given holding potential. Standard P/4 procedure was used to study gating currents in the same axons. We found that the membrane capacity Cm (omega) is voltage as well as frequency dependent. For any given V, the voltage-dependent part of the membrane capacitance has a maximum as the frequency approaches zero and requires at least a two-time constant equivalent circuit to be described. When the holding potential is varied, the voltage-dependent capacitance follows a bell-shaped curve with a maximum change of 0.15 muF/cm2 at about --60 mV. With the pulse method, the maximum is at --40 mV for HP = --70 and it shifts to --70 mV for HP = 0. The shift in the maximum of the voltage-dependent capacitance is consistent with the shift in the charge (Q) vs. V curve observed in our experiments with regular P/4 procedure when the HP is varied. Our data can be explained qualitatively by a four-state model for the sodium channel gating, where a charged particle can move within the field and interact with another particle not affected by the field.


Continued synthesis of bacterial DNA after infection by bacteriophage T4.
Early in infection by bacteriophage T4, before replication has commenced, one can detect the presence of newly synthesized DNA which cosediments with parental phage DNA on sucrose gradients. As shown earlier (R. E. Murray and C. K. Mathews, 1969), some of this represents covalent attachment of new material to parental phage DNA molecules. However, as shown herein, most of it is bacterial DNA, which is synthesized after infection and presumably degraded to T4 DNA-sized pieces. The small amount of phage-specific DNA synthesis which occurs is apparently a repair process, for its extent is greatly increased if the phage are irradiated with ultraviolet light prior to infection. Analysis by means of pulse labeling with [(3)H]thymidine and DNA-DNA hybridization shows that host DNA synthesis continues at a significant rate (40 to 80% of the preinfection rate) as late as 10 min after infection at 37 C. Very early in infection this is primarily replicative synthesis, but later a repair process predominates. Presumably this represents attempted repair of damage being inflicted on host DNA by phage-coded nucleases.


Comparison of antifungal activity of essential oils from different plants against three fungi.
The antifungal activity of plant essential oils (EOs) extracted by steam distillation from seven different species (Cinnamon, Anise, Clove, Citronella, Peppermint, Pepper, and Camphor) was investigated. Three common fungi were isolated from moldy wheat bread, which were identified as Aspergillus niger, A. oryzae, and A. ochraceus. The antifungal activity of anise, peppermint, clove, cinnamon, pepper, citronella, and camphor EOs from seven different spices was confirmed by agar diffusion assay against three fungi. Among all the EOs, the cinnamon EO showed the highest antifungal activity for all the fungi strains with the largest inhibition zone at the concentration of 800 mg/mL and lowest MIC ranging from 0.0625 to 0.125 mg/mL, followed by clove EO. The remaining EOs exerted moderate inhibitory effects. Further research indicated the substantial inhibitory activities of cinnamon and clove EOs on mycelial growth and spore germination in a dose-dependent manner. Further, the in vivo inhibitory activity of selected EOs on naturally infected bread demonstrated that cinnamon and clove EOs can as be used as natural antifungal agents.


Noise can speed convergence in Markov chains.
A new theorem shows that noise can speed convergence to equilibrium in discrete finite-state Markov chains. The noise applies to the state density and helps the Markov chain explore improbable regions of the state space. The theorem ensures that a stochastic-resonance noise benefit exists for states that obey a vector-norm inequality. Such noise leads to faster convergence because the noise reduces the norm components. A corollary shows that a noise benefit still occurs if the system states obey an alternate norm inequality. This leads to a noise-benefit algorithm that requires knowledge of the steady state. An alternative blind algorithm uses only past state information to achieve a weaker noise benefit. Simulations illustrate the predicted noise benefits in three well-known Markov models. The first model is a two-parameter Ehrenfest diffusion model that shows how noise benefits can occur in the class of birth-death processes. The second model is a Wright-Fisher model of genotype drift in population genetics. The third model is a chemical reaction network of zeolite crystallization. A fourth simulation shows a convergence rate increase of 64% for states that satisfy the theorem and an increase of 53% for states that satisfy the corollary. A final simulation shows that even suboptimal noise can speed convergence if the noise applies over successive time cycles. Noise benefits tend to be sharpest in Markov models that do not converge quickly and that do not have strong absorbing states.


iPads and the Use of "Apps" by Children with Autism Spectrum Disorder: Do They Promote Learning?
The advent of electronic tablets, such as Apple's iPad, has opened up the field of learning via technology, and the use of electronic applications ("apps") on these devices continues to dramatically rise. Children with communication and social impairment, specifically those with Autism Spectrum Disorder (ASD), often use educational and recreational apps within the context of their home and school settings. Here we examine in which contexts learning via this medium may be beneficial, and outline recommendations for the use of electronic tablets and the design features for apps to promote learning in this population that is characterized by a unique profile of needs and heterogeneous ability levels.


Nitric oxide: a multitasked signaling gas in plants.
Nitric oxide (NO) is a gaseous reactive oxygen species (ROS) that has evolved as a signaling hormone in many physiological processes in animals. In plants it has been demonstrated to be a crucial regulator of development, acting as a signaling molecule present at each step of the plant life cycle. NO has also been implicated as a signal in biotic and abiotic responses of plants to the environment. Remarkably, despite this plethora of effects and functional relationships, the fundamental knowledge of NO production, sensing, and transduction in plants remains largely unknown or inadequately characterized. In this review we cover the current understanding of NO production, perception, and action in different physiological scenarios. We especially address the issues of enzymatic and chemical generation of NO in plants, NO sensing and downstream signaling, namely the putative cGMP and Ca(2+) pathways, ion-channel activity modulation, gene expression regulation, and the interface with other ROS, which can have a profound effect on both NO accumulation and function. We also focus on the importance of NO in cell-cell communication during developmental processes and sexual reproduction, namely in pollen tube guidance and embryo sac fertilization, pathogen defense, and responses to abiotic stress.


Focusing on the brighter side of Sevoflurane: Realizing true potential of an anesthetic agent as a regulator of cell signaling pathways and microRNAs in different cancers.
Reconceptualization of different anesthetics as anticancer agents has opened new horizons for a better and sharper analysis of true potential of Sevoflurane as a promising and frontline candidate in the pipeline of anticancer agents. Sevoflurane mediated regulation of cell signaling pathways and non-coding RNAs has leveraged our understanding to another level. There have been remarkable advancements in unraveling mechanistic insights related to the ability of sevoflurane to modulate microRNAs in different cancers. Astonishingly, sevoflurane mediated regulation of miRNAs and long non-coding RNAs have been more comprehensively addressed in ischemia-reperfusion injuries. However, researchers yet have to gather missing pieces of premium research-work to uncover mechanistic regulation of long non-coding RNAs by sevoflurane in various cancers. Sevoflurane modulated control of miRNAs have been reported in glioma, colorectal cancer, breast cancer and hepatocellular carcinoma. In this review we have attempted to summarize most recent cutting edge and high-impact experimental researches which have elucidated myriad of underlying mechanisms modulated by sevoflurane to inhibit cancer development and progression. Despite some of the amazing pharmacological properties of sevoflurane, it has been shown to possess darker side because of its involvement in positive regulation of metastasis. In accordance with this notion we have also summarized how sevoflurane enhanced migratory potential of different cancer cells in a separate section. Therefore, these aspects have to be tested in better designed experimental models to identify most relevant types of cancers which can be therapeutically targeted by sevoflurane.


How to identify and prioritize procedures suitable for simulation-based training: Experiences from general needs assessments using a modified Delphi method and a needs assessment formula.
Simulation-based training (SBT) is a revolutionary addition to the education of residents in different specialties. However, the selection of training programs is often reliant on commercially available equipment or on experiential notions, local interests or coincidence. The first step to developing training programs should be problem identification and general needs assessment to ensure that these are aligned with current trainee needs. We describe a stepwise approach to performing a needs assessment following the Delphi process and using a needs assessment formula (NAF) to prioritize technical procedures for simulation training. This technique relies on a panel of experts to gather information and achieve a convergence of opinion. We used three rounds of survey iterations. Round 1: A brainstorming phase to gather all procedures that a newly qualified resident should be able to perform. Round 2: Rating and preliminary prioritization with a NAF including frequency of the procedure, number of doctors, impact, and feasibility. Round 3: Elimination and final prioritization of procedures. The needs assessment identifies and prioritizes procedures for simulation training. It can guide medical educators in the planning of SBT programs to address current trainee needs with the aim of improving the education and training of future doctors.


Does the panoramic radiography have the power to identify the gonial angle in orthodontics?
The objective of this study was to assess gonial angle under the angle classification by comparing panoramic radiograph and lateral cephalometric radiograph. 49 patients (25 males, 24 females) with an age range of 12-29 years participated in the present study. Subjects were retrospectively selected among those categorised as skeletal and dental Class I, II, and III malocclusion group. Using lateral cephalometric radiograph, mandibular and ramal planes were drawn and based on these planes. Gonial angle was determined from two tangents which were drawn from the inferior border of the mandible and posterior borders of the condyle and ramus of both sides in the panoramic radiographs. Multiple comparison tests (ANOVA) were used to determine differences between the three angle groups. There were no significant differences between Class I, II, and III malocclusion group values of gonial angles determined by lateral cephalometric radiograph and panoramic radiographs (P > 0.05). Panoramic radiograph results were shown to be as reliable as lateral cephalometric radiograph in all angle classifications. Panoramic radiography can be used as an alternative radiographic technique to detect gonial angle in orthodontic patients.


Hepatitis B Virus Reactivation Associated With Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus: A Review of Cases Reported to the U.S. Food and Drug Administration Adverse Event Reporting System.
Direct-acting antiviral agents (DAAs) are used increasingly to treat hepatitis C virus (HCV) infection. Reports were published recently on hepatitis B virus (HBV) reactivation (HBV-R) in patients with HBV-HCV co-infection. Hepatitis B virus reactivation, defined as an abrupt increase in HBV replication in patients with inactive or resolved HBV infection, may result in clinically significant hepatitis. To assess whether HBV-R is a safety concern in patients receiving HCV DAAs. Descriptive case series. U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). 29 patients with HBV-R receiving HCV DAAs. Clinical and laboratory data. The FDA identified 29 unique reports of HBV-R in patients receiving DAAs from 22 November 2013 to 15 October 2016. Two cases resulted in death and 1 case in liver transplantation. Patients in whom HBV-R developed were heterogeneous regarding HCV genotype, DAAs received, and baseline HBV characteristics. At baseline, 9 patients had a detectable HBV viral load, 7 had positive results on hepatitis B surface antigen (HBsAg) testing and had an undetectable HBV viral load, and 3 had negative results on HBsAg testing and had an undetectable HBV viral load. For the remaining 10 patients, data points were not reported or the data were uninterpretable. Despite provider knowledge of baseline HBV, HBV-R diagnosis and treatment were delayed in 7 cases and possibly 7 others. The quality of information varied among reports. Because reporting is voluntary, HBV-R associated with DAAs likely is underreported. Hepatitis B virus reactivation is a newly identified safety concern in patients with HBV-HCV co-infection treated with DAAs. Patients with a history of HBV require clinical monitoring while receiving DAA therapy. Studies would help determine the risk factors for HBV-R, define monitoring frequency, and identify patients who may benefit from HBV prophylaxis and treatment. DAAs remain a safe and highly effective treatment for the management of HCV infection. None.


Guttation Fluid: Effects on Growth of Claviceps purpurea in vitro.
In laboratory inoculation experiments, Rosen rye seedlings were more susceptible, Genesee wheat seedlings were less susceptible, and Trail barley seedlings were not susceptible to Claviceps purpurea. Guttation fluids from these plants were used as media for the growth of germinating spores of C. purpurea. Growth experiments consisted of spores which were germinated in thin agar films on microscope slides. Germ tube growth was determined by counting the tubes that crossed the perimeter of a square in the microscope field, counting the conidia in the square, and computing the number of crosses per conidium. Rye guttation fluid produced the most growth and barley fluid the least. Thus the degree of susceptibility is correlated with the amount of growth of the parasite in vitro.


Maturation of ovarian follicles in the prepubertal gilt.
The processes of follicle development and puberty are closely related, and both are associated with maturation of the hypothalamic-pituitary-ovarian axis. Prenatal development of the ovary is independent of gonadotrophic stimulation. Beyond 60 days of age (postnatally), tertiary follicles develop and gonadotrophins begin to influence ovarian follicular development. Negative feedback regulation of pituitary gonadotrophins by ovarian secretions develops between 60 and 100 days of age. In the prepubertal gilt, no consistent changes in peripheral FSH, oestrogen or progesterone concentrations have been identified which are associated with recruitment of the first set of preovulatory follicles. Whether LH secretion increases before this recruitment remains equivocal. Few details are available on how gonadotrophic hormones stimulate ovarian function in the prepubertal gilt. On the basis of a follicular maturation model that has been described for the rat, the actions of FSH, LH and oestrogens on follicular cell receptors and the regulation of aromatase activity seem paramount. Aromatization of androgens to oestrogens has been proposed as a central regulator for follicular maturation. In the prepubertal gilt, a selective increase in peripheral FSH concentration occurs on Day 1 after unilateral ovariectomy, followed by significant increases in ovarian venous concentrations of oestradiol and inhibin on Days 2 and 4 and compensatory growth as measured by follicular fluid volume on Days 2, 4 and 8. Administration of pig follicular fluid to the prepubertal gilt during and after unilateral ovariectomy suppresses compensatory ovarian hypertrophy by mechanisms yet to be determined. In pigs a number of intraovarian factors have been identified, but there is little information on how these factors regulate follicular recruitment and growth. The factor(s) that prevents ovarian follicles in the prepubertal gilt from progressing to ovulation after acquiring the ability to ovulate in response to exogenous gonadotrophins remains unknown.


Nearly a decade-long repeatable seasonal diversity patterns of bacterioplankton communities in the eutrophic Lake Donghu (Wuhan, China).
Uncovering which environmental factors govern community diversity patterns and how ecological processes drive community turnover are key questions related to understand the community assembly. However, the ecological mechanisms regulating long-term variations of bacterioplankton communities in lake ecosystems remain poorly understood. Here we present nearly a decade-long study of bacterioplankton communities from the eutrophic Lake Donghu (Wuhan, China) using 16S rRNA gene amplicon sequencing with MiSeq platform. We found strong repeatable seasonal diversity patterns in terms of both common (detected in more than 50% samples) and dominant (relative abundance >1%) bacterial taxa turnover. Moreover, community composition tracked the seasonal temperature gradient, indicating that temperature is a key environmental factor controlling observed diversity patterns. Total phosphorus also contributed significantly to the seasonal shifts in bacterioplankton composition. However, any spatial pattern of bacterioplankton communities across the main lake areas within season was overwhelmed by their temporal variabilities. Phylogenetic analysis further indicated that 75%-82% of community turnover was governed by homogeneous selection due to consistent environmental conditions within seasons, suggesting that the microbial communities in Lake Donghu are mainly controlled by niche-based processes. Therefore, dominant niches available within seasons might be occupied by similar combinations of bacterial taxa with modest dispersal rates throughout different lake areas.


The pathological basis for skeletal scintigraphy.
Skeletal scintigraphy, which has now been established as a useful and accurate method of detecting early skeletal metastases and assessing their response to treatment, has been investigated for its pathological basis. Histological examination of several hyndred necropsy specimens, from sixty-eight patients who died from malignant disease, showed a significant increase of osteoid and immature woven bone in the presence of metastatic cancer. Tumour-cell suspensions of the VX2 carcinoma were injected into the medullary cavity or on to the periosteal surface of the ilia or tibiae of New Zealand white rabbits. A combination of bone destruction and new bone formation, similar to the autopsy material, was seen. There were at least two mechanisms for the new bone production. Initially, intramembranous ossification was seen in the fibrous stroma surrounding the tumour. Once the cortex was involved and cortical bone destruction had occurred, large amounts of woven bone resembling fracture callus were laid down. The new bone had a markedly increased avidity for bone-seeking isotopes, indicating why skeletal scintigraphy was useful. A further twenty rabbits, in whose ilia the VX2 carcinoma was growing, were treated by local irradiation. When treatment was successful the tumour was destroyed, the production of new bone ceased, and the lesion lost its increased avidity for bone-seeking isotopes, indicating that skeletal scintigraphy could be used to assess the response of skeletal metastases to therapy.


Effect of maternal iodine supplementation on thyroid function and birth outcome in goiter endemic areas.
The study was undertaken to examine the clinical and endocrine parameters of thyroid in a total of 460 pregnant women belonging to non-goiter areas (group 1; n = 156) and endemic areas without (group 2; n = 154) and with iodine supplementation (group 3; n = 150), and their respective newborns. Women of group 3 with visible goiter were administered two capsules of iodized oil orally each containing 200 mg of iodine, from weeks 6--8 of pregnancy. Blood samples were obtained from all groups during each trimester, at parturition (umbilical cord blood) and after delivery. Serum triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) levels were measured by specific enzyme immunoassays. In group 2, serum T4 concentrations were low while T3 and TSH levels were high which showed hypothyroidism in the women of endemic areas. Goiter size decreased in most of the subjects who received a single dose of iodized oil and resulted in increase in serum concentrations of thyroid hormones; whereas, TSH levels decreased. Iodine supplementation also resulted in raised T4 and low TSH levels in the cord blood of neonates. During the course of study, two abortions, three still births and one cretin were reported in group 2; none was reported in group 3; and one still birth was reported in group 1. The oral administration of a single dose of iodized oil is capable of correcting iodine deficiency both clinically and endocrinologically in mothers and neonates. Iodine supplementation has the potential to positively impact the birth weight of newborns.


13C NMR chemical shift of single-wall carbon nanotubes.
We compute the magnetic shielding tensor within the London approximation and estimate the Knight shift of single-wall carbon nanotubes. Our results indicate that high resolution 13C NMR should be able to separate the metallic and insulator character of the nanotubes since a 11 ppm splitting is predicted from the respective resonances. As a model for disorder, bending, and defects in these structures, we investigate the magnetic response of nanotubes with finite size. We get a small line broadening coming from an intrinsic length dependent resonance effect. The nanotube packing is also studied and leads to a 20 ppm broadening which disappears under experimental high-resolution conditions.


Hydrogen Peroxide-induced Cell Death in Mammalian Cells.
Hydrogen peroxide (H2O2) is an important intra- and extra-cellular signaling molecule that can determine cell fate. At low concentrations, H2O2 plays roles in proliferation, immunity, and metabolism. Cellular exposure to higher non-physiologic concentrations of H2O2 can result in oxidative stress. If the stress is not alleviated, cell death can ensue. In the past, few studies were done to study the key mediators of H2O2-induced cell death. The advancement of genetic screening technology with CRISPR/Cas9 tools has allowed for in depth genome-wide studies to identify key mediators in different cell types. Here, we briefly explore the role of H2O2 in the cell and the essential mediators of H2O2-induced cell death with a focus on riboflavin, an unexpected essential mediator of H2O2-induced cell death.


High lithium levels in tobacco may account for reduced incidences of both Parkinson's disease and melanoma in smokers through enhanced β-catenin-mediated activity.
Parkinson's disease (PD) patients have higher rates of melanoma and vice versa, observations suggesting that the two conditions may share common pathogenic pathways. β-Catenin is a transcriptional cofactor that, when concentrated in the nucleus, upregulates the expression of canonical Wnt target genes, such as Nurr1, many of which are important for neuronal survival. β-Catenin-mediated activity is decreased in sporadic PD as well as in leucine-rich repeat kinase 2 (LRRK2) and β-glucosidase (GBA) mutation cellular models of PD, which is the most common genetic cause of and risk for PD, respectively. In addition, β-catenin expression is significantly decreased in more aggressive and metastatic melanoma. Multiple observational studies have shown smokers to have significantly lower rates of PD as well as melanoma implying that tobacco may contain one or more elements that protect against both conditions. In support, smoker's brains have significantly reduced levels of α-synuclein, a pathological intracellular protein found in PD brain and melanoma cells. Tobacco contains very high lithium levels compared to other plants. Lithium has a broad array of neuroprotective actions, including enhancing autophagy and reducing intracellular α-synuclein levels, and is effective in both neurotoxin and transgenic preclinical PD models. One of lithium's neuroprotective actions is enhancement of β-catenin-mediated activity leading to increased Nurr1 expression through its ability to inhibit glycogen synthase kinase-3 β (GSK-3β). Lithium also has anti-proliferative effects on melanoma cells and the clinical use of lithium is associated with a reduced incidence of melanoma as well as reduced melanoma-associated mortality. This is the first known report hypothesizing that inhaled lithium from smoking may account for the associated reduced rates of both PD and melanoma and that this protection may be mediated, in part, through lithium-induced GSK-3β inhibition and consequent enhanced β-catenin-mediated activity. This hypothesis could be directly tested in clinical trials assessing lithium therapy's ability to affect β-catenin-mediated activity and slow disease progression in patients with PD or melanoma.


Visual Tracking via Dynamic Graph Learning.
Existing visual tracking methods usually localize a target object with a bounding box, in which the performance of the foreground object trackers or detectors is often affected by the inclusion of background clutter. To handle this problem, we learn a patch-based graph representation for visual tracking. The tracked object is modeled by with a graph by taking a set of non-overlapping image patches as nodes, in which the weight of each node indicates how likely it belongs to the foreground and edges are weighted for indicating the appearance compatibility of two neighboring nodes. This graph is dynamically learned and applied in object tracking and model updating. During the tracking process, the proposed algorithm performs three main steps in each frame. First, the graph is initialized by assigning binary weights of some image patches to indicate the object and background patches according to the predicted bounding box. Second, the graph is optimized to refine the patch weights by using a novel alternating direction method of multipliers. Third, the object feature representation is updated by imposing the weights of patches on the extracted image features. The object location is predicted by maximizing the classification score in the structured support vector machine. Extensive experiments show that the proposed tracking algorithm performs well against the state-of-the-art methods on large-scale benchmark datasets.


[Structure and venous vascular bed of the rectum in Stavropol breed sheep].
This investigation was aimed at the study of macromorphology of the rectum, including its intramural and extraorgan venous vascular bed in 18-month-old sheep of Stavropol breed. The methods used included anatomical preparation, morphometry, contrast mass intravascular injection, separation of an intestinal wall into the individual layers and preparation of total samples. The thickness of rectal muscular coat in 18-month-old sheep was found to increase in the caudal direction which is interpreted as an adaptation of the intestine for the evacuation of condensed fecal masses through the anal canal lumen. Intramural rectal venous vascular bed included three plexuses: submucosal, muscular and subserosal. The prevalence of the veins of wide-field type with an index of 90-120 in the rectal wall of a sheep results in the deceleration of the venous blood flow in the organ. At the same time, rectal intramural venous vascular bed possesses higher adaptive capacity in the cases of occlusion of the basic roots due to the well developed collateral network located between the roots of wide-field veins. The major extraorgan venous vessel of sheep rectum is a cranial rectal vein. Presence of its terminoterminal anastomoses with caudal rectal and left colonic veins may provide a bypass rectal venous blood flow in the cases of a the obstruction of one of its major vessels of various etiology.


[The diagnosis of ghost cell glaucoma with methyl violet stain].
The diagnosis in 30 cases of ghost cell glaucoma was confirmed by the method of 1% methyl violet staining, which was simple, convenient and pathognomonic. The authors believed that ghost cells could develop both in the anterior chamber and in the vitreous. Since the hypotensive effect was marked, treatment should not be neglected even for cases with no light perception.


Effects of Helicobacter pylori Infection on the Prognosis of Chronic Atrophic Gastritis by Inducing the Macrophage Polarization.
Recently, the effects of Helicobacter pylori (H. pylori) infection on the prognosis of chronic atrophic gastritis (CAG) are still unclear. The aim of our study was to discuss the role of H. pylori infection on the prognosis of CAG by inducing the M1/M2 macrophage polarization. A total of 180 subjects as control (group 1), CAG patients without H. pylori infection (group 2) and H. pylori-associated CAG patients (group 3) were respectively recruited for this cross-sectional investigation in Daqing Oilfield General Hospital from May 2019 to July 2020. Their serum samples were collected to determine the concentrations of pro-inflammatory and anti-inflammatory cytokines. Meanwhile, the gastric mucosa was excised to determine the related gene expressions on the M1/M2 macrophage polarization. Then the prognosis of CAG was evaluated according to the status of clinical manifestations and endoscopic examination after the follow-up. Notably, it was proved that compared with the control group, the expressions and concentrations of pro-inflammatory cytokines (M1 macrophage: inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-6 (IL-6)) were significantly higher, while the anti-inflammatory cytokines (M2 macrophage: arginase-1 (Arg-1), IL-4 and IL-10) were apparently reduced in the group 2 and group 3 (P < 0.05). Moreover, more days were needed for the prognosis of CAG in group 3 than those in group 2, which was accompanied by higher expressions of pro-inflammatory and lower anti-inflammatory cytokines at the baseline (P < 0.05). Furthermore, negative correlations were shown between the concentrations of iNOS, TNF-α, IFN-γ and IL-6, and the prognosis of CAG (P < 0.05), while positive correlations were observed between the contents of IL-4 and IL-10, and prognosis of CAG (P < 0.05). These above results indicated that H. pylori infection-induced disorders of M1/M2 macrophage polarization could affect the prognosis of CAG.


Asbestos between science and myth. A 6,000-year story.
Asbestos was used in making pottery in Eastern Finland from around 4000 B.C. In the ancient era and in the Middle Ages, magic properties were frequently attributed to this mineral. In the first century A.D., the Latin encyclopaedist Pliny the Elder reported in his Historia Naturalis that asbestos protects against all poisonings, particularly that of magicians. Moreover, asbestos was often found in places of worship, in Rome as well as in Athens and in Jerusalem. In the Middle Ages asbestos was identified with some animals, such as the salamander and certain white rodents. With such appearance, the mineral had a huge success in Western as well as in Eastern literature and the fine arts. Marco Polo (1254-1324) in the Milione tried to deny that asbestos was a salamander. Despite its noxious effects, asbestos continues to be used in much of the world. In the 21st century it seems to be maintaining its quality as a magic stone.


[Alpha-lipoic--dihydrolipoic acids--active bioantioxidant and bioregulatory system].
alpha-Lipoic (LA) acid (thioctic acid) is an intramolecular disulfide that may be simply endogenically turned into dithiol. Dihydrolipoic acid (DHLA)/ LA and DHLA are bioantioxidants. They are synthesized in the body and taken with diet. Water- and lipide-soluble LA is highly-effective against the reactive oxygen species. LA (DHLA) protect the biomembranes, mitochondria from oxidative stresses of various kinds. LA, DHLA and lipoamide function as cofactors of polyenzyme mitochondrial complexes of 2-oxoacid dehydrogenases, of glycin decarboxylases and of some other enzymes. LA (DHLA) is ubiquinone reactivator and synergist by vitamin A, C, E. LA optimizes glucose metabolism, it is effective in insulin-resistant diabetes and its complications, in neutopathies and neurodegenerative diseases.


Tyr115, gln165 and trp209 contribute to the 1, 2-epoxy-3-(p-nitrophenoxy)propane-conjugating activity of glutathione S-transferase cGSTM1-1.
We investigated the epoxidase activity of a class mu glutathione S-transferase (cGSTM1-1), using 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) as substrate. Trp209 on the C-terminal tail, Arg107 on the alpha4 helix, Asp161 and Gln165 on the alpha6 helix of cGSTM1-1 were selected for mutagenesis and kinetic studies. A hydrophobic side-chain at residue 209 is needed for the epoxidase activity of cGSTM1-1. Replacing Trp209 with histidine, isoleucine or proline resulted in a fivefold to 28-fold decrease in the k(cat)(app) of the enzyme, while a modest 25 % decrease in the k(cat)(app) was observed for the W209F mutant. The rGSTM1-1 enzyme has serine at the correponding position. The k(cat)(app) of the S209W mutant is 2. 5-fold higher than that of the wild-type rGSTM1-1. A charged residue is needed at position 107 of cGSTM1-1. The K(m)(app)(GSH) of the R107L mutant is 38-fold lower than that of the wild-type enzyme. On the contrary, the R107E mutant has a K(m)(app)(GSH) and a k(cat)(app) that are 11-fold and 35 % lower than those of the wild-type cGSTM1-1. The substitutions of Gln165 with Glu or Leu have minimal effect on the affinity of the mutants towards GSH or EPNP. However, a discernible reduction in k(cat)(app) was observed. Asp161 is involved in maintaining the structural integrity of the enzyme. The K(m)(app)(GSH) of the D161L mutant is 616-fold higher than that of the wild-type enzyme. In the hydrogen/deuterium exchange experiments, this mutant has the highest level of deuteration among all the proteins tested. We also elucidated the structure of cGSTM1-1 co-crystallized with the glutathionyl-conjugated 1, 2-epoxy-3-(p-nitrophenoxy)propane (EPNP) at 2.8 A resolution. The product found in the active site was 1-hydroxy-2-(S-glutathionyl)-3-(p-nitrophenoxy)propane, instead of the conventional 2-hydroxy isomer. The EPNP moiety orients towards Arg107 and Gln165 in dimer AB, and protrudes into a hydrophobic region formed by the loop connecting beta1 and alpha1 and part of the C-terminal tail in dimer CD. The phenoxyl ring forms strong ring stacking with the Trp209 side-chain in dimer CD. We hypothesize that these two conformations represent the EPNP moiety close to the initial and final stages of the reaction mechanism, respectively.


Back to the future: The intimate and evolving connection between telomere-related factors and genotoxic stress.
The conversion of circular genomes to linear chromosomes during molecular evolution required the invention of telomeres. This entailed the acquisition of factors necessary to fulfill two new requirements: the need to fully replicate terminal DNA sequences and the ability to distinguish chromosome ends from damaged DNA. Here we consider the multifaceted functions of factors recruited to perpetuate and stabilize telomeres. We discuss recent theories for how telomere factors evolved from existing cellular machineries and examine their engagement in nontelomeric functions such as DNA repair, replication, and transcriptional regulation. We highlight the remarkable versatility of protection of telomeres 1 (POT1) proteins that was fueled by gene duplication and divergence events that occurred independently across several eukaryotic lineages. Finally, we consider the relationship between oxidative stress and telomeres and the enigmatic role of telomere-associated proteins in mitochondria. These findings point to an evolving and intimate connection between telomeres and cellular physiology and the strong drive to maintain chromosome integrity.


[The relationship of the inferior mesenteric vein with arteries].
The investigation was based on the results of roentgen-anatomical study of 155 digestive tract complexes obtained from 155 cadavers of humans of both genders aged 17-90 years. It was established that in 91% (in 141 of 155) of the cases the trunk of the inferior mesenteric vein (IMV) was accompanied by the arteries only in the lower part (by inferior mesenteric artery) and in the middle part (by the left colic artery). The terminal part of IMV was separated from the artery. In 9% of (in 14 of 155) cases the trunk of the IMV is accompanied along the whole extent by different arteries (from down upwards): by inferior mesenteric artery and left colic artery from inferior mesenteric artery, and in its terminal part either by an additional anastomosis between the superior and inferior mesenteric arteries (in 5 of 14 cases), or by an additional anastomosis between superior and inferior mesenteric arteries and the branch or trunk of the proximal colic artery from the superior mesenteric artery (in 9 of 14 cases).


Treatment of an autoimmune encephalomyelitis mouse model with nonmyeloablative conditioning and syngeneic bone marrow transplantation.
Hematopoietic stem cell transplantation (HSCT) has been proposed as a novel therapy for multiple sclerosis (MS). CD4 + CD25 + regulatory T cells (Tregs) expressing Foxp3 play an important role in the maintenance of immune tolerance to self. Our study was conducted to confirm the efficiency of nonmyeloablative conditioning and syngeneic bone marrow transplantation (BMT) on experimental autoimmune encephalomyelitis (EAE) mice and to determine whether Tregs plays a role in the underlying mechanism. EAE were induced in C57BL/6 mice and were randomly divided into 4 groups: the Conditioning group received the conditioning regimen, the Normal-EAE BMT group received conditioning and bone marrow (BM) grafts from normal mice, the EAE-EAE BMT group received conditioning and BM grafts from EAE mice and the EAE control group received no further therapy. The cumulative clinical score was used to assess the efficacy of the different treatments, and the proportion of Tregs in the spleen was measured by flow cytometry on day 40, 80 and 120 after BMT. Foxp3 mRNA expression was assessed by real-time PCR, and the expression of Foxp3 protein was tested by western blot on day 120 after BMT. Conditioning and conditioning with BMT led to a significant clinical improvement on day 80 after BMT compared with EAE without further treatment. On day 120 after BMT, the clinical score of the Conditioning group showed no significant difference from that of the EAE control group, whereas BMT led to a further amelioration of the disease score. On day 80 and day 120 after BMT, the proportions of Tregs of the two BMT groups were significantly higher than that in EAE control group, whereas no statistically significant difference was found between the Conditioning group and the EAE control group. On day 120 after BMT, the Foxp3 mRNA level and Foxp3 protein expression was higher in the two BMT groups than in EAE control group or Conditioning group. Nonmyeloablative conditioning could temporarily reverse already established EAE, but it was not sufficient for the induction of long-term EAE remission. Transplantation by BM cells from healthy or diseased donors was necessary and responsible for complete and long-time remission of EAE, and these beneficial effects may be the result of the induction of Tregs and the Treg-related factor Foxp3.


Physicochemical characteristics and pollen spectra of organic and non-organic honey samples of Apis mellifera L.
The aim of this research was to analyze and compare 17 honey samples, 11 organic and six non-organic Apis mellifera honey. The samples were analyzed concerning moisture, hydroxymethylfurfural, diastase index, water activity, color, total sugar, reducing sugar, sucrose, ash, viscosity, electrical conductivity, pH, acidity, and formol index. With the exception of acidity, reducing sugar and diastase index, the averages of other parameters were different between the two groups. All samples of organic honey presented moisture values between 23.50 and 24.40%. Among the nonorganic honey samples, two presented apparent sucrose amount upper the maximum limit established by the Brazilian Legislation. According to the quantitative analysis of pollen sediments in the honey samples and frequency of pollen types in 17 honey samples, 41.20% were classified as unifioral, and the remainder as polifioral.


ANALYSIS OF DEFECTS IN THE FORENSIC MEDICAL ASSESSMENT OF CHANGES DISCOVERED DURING THE EXAMINATION OF PERSONS WHO DIED FROM TRAUMATIC BRAIN INJURY.
The aim: To identify the main groups of expert defects that arise during the forensic assessment of changes detected during the examination of persons who died from a traumatic brain injury (TBI). Materials and methods: A total of 102 repeated commission forensic medical examinations with changed conclusions in corpses with TBI were analyzed. Data processing and analysis were conducted using statistical methods. Results: The examined forensic medical assessments of TBI with changed conclusions in corpses were categorized into the following groups: defects in estab¬lishing the diagnosis of TBI - 17.65±7.4%; defects in establishing the mechanism of TBI - 35.3±9.3%; defects in establishing the duration of TBI - 39.22±9.5%: sober - 20±12.4%; with alcohol intoxication - 80±12.4%. A combination of defects was found in 7.83±5.2% of cases. Defects that directly affected the experts' incorrect establishment of the diagnosis, mechanism, and duration of TBI were also identified. Conclusions: The largest number of changed conclusions during the forensic medical examination of corpses in cases of TBI was due to the wrongly established duration of the trauma, accounting for 39.2±9.5%, with the vast majority of cases (80±12.4%) observed against the background of alcohol intoxication. The mechanism of trauma accounted for 35.3±9.3% of the changed conclusions. The main defects were incomplete collection of material for histological examination (90.2±5.8%) and incorrect interpretation of the results of histological examination (76.48±8.2%), along with the violation of the method of sectional examination (68.6±9.0%). Different groups of expert defects predominated in the cases with an incorrectly established diagnosis of TBI, duration of trauma, and mechanism.


Circadian and photic regulation of phosphorylation of ERK1/2 and Elk-1 in the suprachiasmatic nuclei of the Syrian hamster.
In this study we investigated the circadian and photic regulation of phosphorylation of the extracellular signal-related kinase (ERK) 1/2, and the transcription factor Elk-1 in the suprachiasmatic nuclei of the Syrian hamster. We report that levels of phosphorylated ERK (P-ERK) are rhythmic, peaking during the mid subjective day, whereas phosphorylated Elk-1 (P-Elk-1) shows no distinct rhythm. Light pulses during the subjective night rapidly, but transiently, induce P-ERK, whereas P-Elk-1 is also induced, albeit with a slower time course. Application of the ERK pathway inhibitor U0126 attenuates photic induction of both P-ERK and P-Elk-1 and phase advances of wheel-running behavior. The NMDA receptor channel blocker, MK-801, also significantly attenuates photic induction of P-ERK and P-Elk-1. Taken together, these results indicate a role of the ERK cascade in the regulation of free-running circadian rhythms and of photic-resetting of these rhythms and suggest that in the mammalian suprachiasmatic nuclei, Elk-1 represents a novel molecular component of the photic-induction pathway.


Effect of chronic high-dose exogenous cortisol on hippocampal neuronal number in aged nonhuman primates.
Chronic exposure to increased glucocorticoid concentrations appears to lower the threshold for hippocampal neuronal degeneration in the old rat. It has been proposed that increased brain exposure to glucocorticoids may lower the threshold for hippocampal neuronal degeneration in human aging and Alzheimer's disease. Here, we asked whether chronic administration of high-dose cortisol to older nonhuman primates decreases hippocampal neuronal number as assessed by unbiased stereological counting methodology. Sixteen Macaca nemestrina (pigtailed macaques) from 18 to 29 years of age were age-, sex-, and weight-matched into pairs and randomized to receive either high-dose oral hydrocortisone (cortisol) acetate (4-6 mg/kg/d) or placebo in twice daily palatable treats for 12 months. Hypothalamic-pituitary-adrenal activity was monitored by measuring plasma adrenocorticotropin and cortisol, 24 hr urinary cortisol, and CSF cortisol. Urinary, plasma, and CSF cortisol were elevated, and plasma adrenocorticotropin was reduced in the active treatment group. Total hippocampal volume, subfield volumes, subfield neuronal density, and subfield total neuronal number did not differ between the experimental groups. These findings suggest that chronically elevated cortisol concentrations, in the absence of stress, do not produce hippocampal neuronal loss in nonhuman primates.