A phase II study of oral piritrexim in recurrent high-grade (III, IV) glioma.
Piritrexim is a lipid-soluble drug which is as effective an inhibitor of dihydrofolate reductase as methotrexate. Phase I and II studies have indicated activity in some tumour types. Because of its lipophilicity we have conducted a phase II study in recurrent high-grade malignant glioma (grades III and IV). Twenty-seven patients were treated with 25 mg p.o. three times daily for five consecutive days, repeated weekly, with provision for dose escalation or reduction according to toxicity. Five patients received less than 4 weeks' treatment because of disease progression or death. Twenty-two patients were evaluable for response. One complete and one partial response was seen (duration 262+ and 241+ weeks) and 13 patients had static disease for a median duration of 13 weeks (range 7-35). The major toxicity was myelosuppression. This response rate of 9% of evaluable patients is much lower than that seen for some conventionally used drugs and we conclude that piritrexim is unlikely to be of value in the management of high-grade gliomas.


Quantifying diffuse contamination: Comparing silver and mercury in organogenic and minerogenic soil.
For both, silver (Ag) and mercury (Hg), the median concentrations in an aqua regia extraction of minerogenic top- and subsoil from continental scale geochemical surveys (Australia, China, Europe) are around 0.02 mg/kg. When the soil O horizon is collected as topsoil sample, the concentration of again both elements is higher by about a factor of 10 (range 7-30), with median concentrations around 0.2 mg/kg Ag and Hg. Geochemical maps of top- and subsoil at different scales for both elements display regional patterns which reflect mainly geology, climate and topography. Anthropogenic sources like mines, power plants, or major cities visually occur only as local anomalies. For Ag in organogenic topsoil the maximum possible input due to diffuse contamination is estimated to be in the 0.02 mg/kg range, about 10% of the median concentration in the soil O horizon. For Hg this value is slightly higher at 0.03 mg/kg. In the soil O horizon Hg concentrations show less variability than in the C horizon. Substantial Hg soil contamination should lead to noticeably increased Hg/Ag ratios.


Regulatory T cells in stem cell transplantation: main characters or walk-on actors?
Almost 10 years have passed since the first experiments specifically addressing the role of regulatory T cells (Treg) in stem cell transplantation (SCT). It is now time to try to dissect what is their actual impact in such a therapeutic context. In the present review we will initially remind the preliminary experiments exploring the Treg behavior in murine models of SCT, then moving to the first studies evaluating their influence on graft versus host disease and graft versus leukemia in humans. After focusing on some interesting aspects of Treg mechanisms of action after SCT, we will evaluate their activity after donor lymphocyte infusion as well as after reduced intensity conditioning and autologous SCT. We will conclude by briefly discussing possible therapeutic applications of Treg and highlighting biological and clinical issues which deserve to be further assessed in the next future.


Novel application of continuously variable transmission system using composite recurrent Laguerre orthogonal polynomials modified PSO NN control system.
Because the V-belt continuously variable transmission system spurred by permanent magnet (PM) synchronous motor has much unknown nonlinear and time-varying characteristics, the better control performance design for the linear control design is a time consuming procedure. In order to overcome difficulties for design of the linear controllers, the composite recurrent Laguerre orthogonal polynomials modified particle swarm optimization (PSO) neural network (NN) control system which has online learning capability to come back to the nonlinear and time-varying of system, is developed for controlling PM synchronous motor servo-driven V-belt continuously variable transmission system with the lumped nonlinear load disturbances. The composite recurrent Laguerre orthogonal polynomials NN control system consists of an inspector control, a recurrent Laguerre orthogonal polynomials NN control with adaptation law and a recouped control with estimation law. Moreover, the adaptation law of online parameters in the recurrent Laguerre orthogonal polynomials NN is originated from Lyapunov stability theorem. Additionally, two optimal learning rates of the parameters by means of modified PSO are posed in order to achieve better convergence. At last, comparative studies shown by experimental results are illustrated to demonstrate the control performance of the proposed control scheme.


Colorimetric assay for the quantification of serum iodixanol concentration and its application on estimation of glomerular filtration rate in cattle.
A colorimetric assay used to quantify the non-ionic contrast medium iodixanol in sera was validated and compared with high-performance liquid chromatography. The application of this assay to estimate glomerular filtration rates (GFR) in cattle was examined. Serum iodixanol was de-iodinated by alkaline hydrolysis and the amount of released iodine was subsequently determined using a ceric arsenite method. There was a close correlation between the two methods using identical specimens. In clinically healthy cattle with different body weights, the reference value (166.3-178.8 mL/min/m(2)) based on body surface area was fairly stable as compared with that (2.13-3.63 mL/min/kg) based on body weight. Based on GFR data in healthy and renal-impaired cattle, when the GFR decreased to more than 60% of the reference value, serum urea nitrogen and creatinine concentrations increased. The colorimetric assay is a simple method for the estimation of GFR in cattle and requires no expensive equipment.


Effects of sub-chronic exposure to SO2 on lipid and carbohydrate metabolism in rats.
Sulfur dioxide (SO2) is a ubiquitous air pollutant, present in low concentrations in the urban air, and in higher concentrations in the working environment. While toxicological reports on SO2 have extensively dealt with the pulmonary system, essentially no data are available on the effects of chronic exposure to this pollutant on intermediary metabolism, although some biochemical changes in lipid metabolism have been detected. The present investigation was aimed at evaluating the effects of sub-chronic exposure to SO2 on concentrations of serum lipids/lipoproteins and on glucose metabolism, in animal models of hypercholesterolemia and diabetes. A specially designed control-inert atmosphere chamber was used, where male Sprague-Dawley rats fed on either standard or cholesterol enriched (HC) diets, as well as streptozotocin diabetics, were exposed to SO2 at 5 and 10 ppm, 24 h per day for 14 days. In rats, both on a standard diet and on a HC regimen, SO2 exposure determined a significant dose-dependent increase in plasma triglycerides, up to +363% in the 10 ppm HC exposed animals. This same gas concentration significantly reduced HDL cholesterol levels. In contrast, exposure of diabetic animals to 10 ppm SO2 resulted in a fall (-41%) of plasma and liver triglycerides and in a concomitant increase (+62%) of plasma HDL cholesterol. This discrepancy could apparently be related to diverging effects of SO2 exposure on plasma insulin levels in the different animal groups. Kinetic analyses of triglyceride synthesis carried out in rats on a standard diet revealed, in exposed animals, a significant reduction in the secretory rate, in spite of the concomitant hypertriglyceridemia. These findings suggest that SO2 exposure can markedly modify major lipid and glycemic indices, also indicating a differential response in normo/hyperlipidemic versus diabetic animals.


Pyrrole-Imidazole Polyamides: Automated Solid-Phase Synthesis.
In this unit, the fully automated solid-phase synthetic strategy of hairpin Py-Im polyamides is described using triphosgene (BTC) as a coupling agent. This automated methodology is compatible with all the typical building blocks, enabling the facile synthesis of polyamide libraries in 9% to 20% yield in 3 days.


SHP2 Regulates the Osteogenic Fate of Growth Plate Hypertrophic Chondrocytes.
Transdifferentiation of hypertrophic chondrocytes into bone-forming osteoblasts has been reported, yet the underlying molecular mechanism remains incompletely understood. SHP2 is an ubiquitously expressed cytoplasmic protein tyrosine phosphatase. SHP2 loss-of-function mutations in chondroid cells are linked to metachondromatosis in humans and mice, suggesting a crucial role for SHP2 in the skeleton. However, the specific role of SHP2 in skeletal cells has not been elucidated. To approach this question, we ablated SHP2 in collagen 2α1(Col2α1)-Cre- and collagen 10α1(Col10α1)-Cre-expressing cells, predominantly proliferating and hypertrophic chondrocytes, using "Cre-loxP"-mediated gene excision. Mice lacking SHP2 in Col2α1-Cre-expressing cells die at mid-gestation. Postnatal SHP2 ablation in the same cell population caused dwarfism, chondrodysplasia and exostoses. In contrast, mice in which SHP2 was ablated in the Col10α1-Cre-expressing cells appeared normal but were osteopenic. Further mechanistic studies revealed that SHP2 exerted its influence partly by regulating the abundance of SOX9 in chondrocytes. Elevated and sustained SOX9 in SHP2-deficient hypertrophic chondrocytes impaired their differentiation to osteoblasts and impaired endochondral ossification. Our study uncovered an important role of SHP2 in bone development and cartilage homeostasis by influencing the osteogenic differentiation of hypertrophic chondrocytes and provided insight into the pathogenesis and potential treatment of skeletal diseases, such as osteopenia and osteoporosis.


Impact of a Streamlined Trauma-Focused Smartphone Application on Protocol Compliance and Delivery of Care.
In November 2015, an institution-specific mobile application (app) was created to provide rapid access to trauma protocols. The app was tested, and the results suggested that the app was difficult to use as it linked to web-based databases. In June 2018, the app was redesigned with protocol infographics and algorithms that are available offline, eliminating the need to scroll through web pages. We tested the redesigned app's ability to provide information quickly, in a user-friendly manner. This was a prospective, experimental analysis of a streamlined, institution-specific trauma app. Participants included general surgery residents, advanced practice providers, and attending trauma surgeons. The primary outcomes of measure were time to complete an exam with trauma scenarios and the number of questions answered correctly. The primary exposure of interest was access to the app during the exam. There were 35 study participants: 17 with the 2018 version of the app to complete the quiz and 18 without app access. The group with access scored higher than those without access (70% versus 50%, P = 0.0005) as well as those with the old version of the app in the 2015 study (70% versus 55%, P = 0.0250). App access eliminated a significant difference in exam scores between residents and attendings that was present without the app. A mobile app with offline access to protocol infographics and algorithms gives providers access to recommended practices and may improve delivery of trauma care. The app is helpful to residents and helps bridge the knowledge gap between groups when the app is not available. Level III.


Distinct MAPK pathways are involved in IL-23 production in dendritic cells cocultured with NK cells in the absence or presence of angiotensin II.
Accumulated evidence suggests that the crosstalk between dendritic cells (DCs) and natural killer (NK) cells enhances each other's capacity, and results in the production of a variety of soluble factors. However, little is known about the effect of DC-NK crosstalk in interleukin-23 (IL-23) production. In the present study we show that DC-NK coculture caused a high expression of IL-23, angiotensin II (Ang II) alone moderately increased IL-23 production in DCs, but decreased IL-23 secretion in the DC-NK coculture system. We found that Ang II does not influence DC maturation in DC-NK crosstalk. We next investigated the mitogen-activated protein kinase (MAPK) pathway in DCs. We found that Ang II increased IL-23 production through the extracellular signal-related kinase (ERK) pathway. All three MAPK members c-Jun N-terminal kinase (JNK), ERK and p38 were involved in IL-23 production in the DC-NK coculture system. In the presence of Ang II, only the JNK pathway seems to play a role in IL-23 production in DCs cocultured with NK. These data suggest that distinct MAPK pathways are involved in IL-23 production in DCs in response to different stimuli. This work demonstrates for the first time that IL-23 is produced in the DC-NK coculture system, and that Ang II is involved in DC-NK crosstalk. This data will act as a resource that allows further exploitation of role of immune response in atherosclerosis.


Functional outcome of traumatic spinopelvic instabilities treated with lumbopelvic fixation.
The aim of this study was to assess the functional outcome after lumbopelvic fixation (LPF) using the SMFA (short musculoskeletal functional assessment) score and discuss the results in the context of the existing literature. The last consecutive 50 patients who underwent a LPF from January 1st 2011 to December 31st 2014 were identified and administered the SMFA-questionnaire. Inclusion criteria were: (1) patient underwent LPF at our institution, (2) complete medical records, (3) minimum follow-up of 12 months. Out of the 50 recipients, 22 questionnaires were returned. Five questionnaires were incomplete and therefore seventeen were included for analysis. The mean age was 60.3 years (32-86 years; 9m/8f) and the follow-up averaged 26.9 months (14-48 months). Six patients (35.3%) suffered from a low-energy trauma and 11 patients (64.7%) suffered a high-energy trauma. Patients in the low-energy group were significantly older compared to patients in the high-energy group (72.2 vs. 53.8 years; p = 0.030). Five patients (29.4%) suffered from multiple injuries. Compared to patients with low-energy trauma, patients suffering from high-energy trauma showed significantly lower scores in "daily activities" (89.6 vs. 57.1; p = 0.031), "mobility" (84.7 vs. 45.5; p = 0.015) and "function" (74.9 vs. 43.4; p = 0.020). Our results suggest that patients with older age and those with concomitant injuries show a greater impairment according to the SMFA score. Even though mostly favorable functional outcomes were reported throughout the literature, patients still show some level of impairment and do not reach normative data at final follow-up.


Neurotrophic Factor Receptors trkB and trkC in Experimental Model of Lesion in Rat Brain Structures in Schizophrenia.
The maldevelopmental model of schizophrenia postulates pathological alterations in embryonal neurogenesis as the etiopathogenetic basis of schizophrenic psychoses. The neurotrophic factor hypothesis explains these neuropathological abnormalities as the result of alterations of the neurotrophin system caused by different mechanisms such as a genetic, infectious and traumatic factors. The tyrosine-kinase containing receptors trkB and trkC mediate growth-promoting effects of neurotrophins and respond to changes in neurotrophic factors availability. The aim of the present study was to establish the expression pattern of trkB and trkC in rat brain structures by a developmental model of schizophrenia. On cryostat coronal brain sections of control and lesioned rats (after infusion of ibotenic acid solution bilaterally into the hippocampal formation), immunoreactions for trkB and trkC were performed. We found diminished expression of trkB and trkC in the hippocampal formation of lesioned animals compared to the controls. Quantitative measurements of immunohistochemical reactions intensity and statistical analysis confi rmed the reduced immunoreactivity for antigens under study (trkB and trkC) in the positive hippocampal neurons of 56-day-old lesioned rats compared to the control animals. The observed downregulation of neurotrophic factor receptors expression may compromise the function and plasticity of hippocampal formation in schizophrenic brains.


Effect of heterogeneous radiosensitivity on the optimal fractionation in radiotherapy.
to determine optimal fractionation schedule which provides maximum biologically effective dose (BED) in the targeted tumor in the case of heterogeneous radiosensitivity of malignant cells in combination with a spatially varying sparing factor for the organ at risk. the mathematical framework used in the current study is based on the linear-quadratic (LQ) model with heterogeneous parameters alpha and beta for malignant cells. To determine optimal fractionation, we consider changes in BED in the treatment target (BEDtar) under the condition of fixed BED in the affected normal tissue (BEDnt). we demonstrate both analytically and via numerical calculations that there exists an optimal number of fractions for which biologically effective dose in the uniformly irradiated target is at maximum. It is also shown that dependence of BEDtar on number of fractions is generally non-monotonic and is affected by the variances σα and σβ of the alpha and beta radiosensitivities, respectively. In a particular case when σα and σβ are sufficiently small, expression for the optimal target dose which maximizes BEDtar was derived analytically. the obtained results demonstrate that in the presence of heterogeneous alpha and beta in the tumor, hypofractionation can either increase or decrease BEDtar depending on the variances σα and σβ. Consequently, intratumor heterogeneity is an important factor which can affect radiobiological comparison of different fractionation regimens.


Gemifloxacin is efficacious against penicillin-resistant and quinolone-resistant pneumococci in experimental meningitis.
In experimental rabbit meningitis, gemifloxacin penetrated inflamed meninges well (22 to 33%) and produced excellent bactericidal activity (change in log(10) [Deltalog(10)] CFU/ml/h, -0.68 +/- 0.30 [mean and standard deviation]), even superior to that of the standard regimen of ceftriaxone plus vancomycin (-0.49 +/- 0.09 deltalog(10) CFU/ml/h), in the treatment of meningitis due to a penicillin-resistant pneumococcal strain (MIC, 4 mg/liter). Even against a penicillin- and quinolone-resistant strain, gemifloxacin showed good bactericidal activity (-0.48 +/- 0.16 deltalog(10) CFU/ml/h). The excellent antibacterial activity of gemifloxacin was also confirmed by time-kill assays over 8 h in vitro.


Analysis of sex and regional differences in androgen receptors in fetal rhesus monkey brain.
Cytosolic androgen receptor levels were measured in different brain regions of fetal male and female rhesus monkeys (day 135 post-conception). The hypothalamus-preoptic area, amygdala and cerebellum exhibited higher receptor concentration in comparison to the cerebral cortex (parietal, temporal frontal, and occipital lobes), hippocampus and cingulate gyrus (P less than 0.001). No sexual difference in receptor concentrations was found except in the amygdala where fetal males exhibited slightly higher levels than females. The similarity in androgen receptor levels suggests that the developing brain of both sexes could be influenced by circulating androgens under normal or pathological conditions.


The dynamic of lipid oxidation in human myotubes.
Both endogenous and exogenous lipid levels may be regulators of total lipid oxidation in skeletal muscles. We studied the dynamics of lipid oxidation in human myotubes established from healthy, lean subjects exposed to acutely and chronically increased palmitate concentrations. The intramyocellular triacylglycerol content increased with chronic palmitate exposure. Both, ectopically increased intracellular and extracellular lipid levels were simultaneously oxidized and could partly suppress each other's oxidation. Overall, the highest acute palmitate treatments stimulated fatty acid oxidation whilst the highest chronic treatments decreased total lipid oxidation. Intracellular lipids showed a more complete oxidation than exogenous lipids. Endogenous lipids reduced insulin-mediated glucose oxidation. Thus, both endogenous and exogenous lipid concentrations regulated each other's oxidation and total lipid oxidation in human myotubes. A reduced exogenous lipid oxidation, secondary to increased triacylglycerol levels, may redirect free fatty acids into esterification and oxidation from intracellular stores, thereby protecting myotubes from FFA lipotoxic effects.


Constituents of buriti oil (Mauritia flexuosa L.) like inhibitors of the SARS-Coronavirus main peptidase: an investigation by docking and molecular dynamics.
Statistics show alarming numbers of infected and killed in the world, caused by the Covid-19 pandemic, which still doesn't have a specific treatment and effective in combating all efforts to seek treatments and medications against this disease. Natural products are of relevant interest in the search for new drugs. Thus, Buriti oil (Mauritia flexuosa L.) is a natural product extracted from the fruit of the palm and is quite common in the legal Amazon region, Brazil. In the present work, the anti-Covid-19 biological activity of some constituents of Buriti oil was investigated using in silico methods of Molecular Docking and Molecular Dynamics Simulations. The main results of Molecular Docking revealed favorable interaction energies in the formation of the 2GTB peptidase complex (main peptidase of SARS-CoV) with the 13-cis-β-carotene ligands (ΔGbind = -10.23Kcal mol-1), 9-cis -β-carotene (ΔGbind = -9.82Kcal mol-1), and α-carotene (ΔGbind = -8.34Kcal mol-1). Molecular Dynamics simulations demonstrated considerable interaction for these ligands with emphasis on α-carotene. Such theoretical results encourage and enable a direction for experimental studies in vitro and in vivo, essential in the development of new drugs with enzymatic inhibitory action for Covid-19.Communicated by Ramaswamy H. Sarma.


When to incorporate point-of-care ultrasound (POCUS) into the initial assessment of acutely ill patients: a pilot crossover study to compare 2 POCUS-assisted simulation protocols.
The purpose of this study was to determine the ideal timing for providers to perform point-of-care ultrasound (POCUS) with the least increase in workload. We conducted a pilot crossover study to compare 2 POCUS-assisted evaluation protocols for acutely ill patients: sequential (physical examination followed by POCUS) vs parallel (POCUS at the time of physical examination). Participants were randomly assigned to 2 groups according to which POCUS-assisted protocol (sequential vs parallel) was used during simulated scenarios. Subsequently, the groups were crossed over to complete assessment by using the other POCUS-assisted protocol in the same patient scenarios. Providers' workloads, measured with the National Aeronautics and Space Administration Task Load Index (NASA-TLX) and time to complete patient evaluation, were compared between the 2 protocols. Seven providers completed 14 assessments (7 sequential and 7 parallel). The median (IQR) total NASA-TLX score was 30 (30-50) in the sequential and 55 (50-65) in the parallel protocol (P = .03), which suggests a significantly lower workload in the sequential protocol. When individual components of the NASA-TLX score were evaluated, mental demand and frustration level were significantly lower in the sequential than in the parallel protocol (40 [IQR, 30-60] vs 50 [IQR, 40-70]; P = .03 and 25 [IQR, 20-35] vs 60 [IQR, 45-85]; P = .02, respectively). The time needed to complete the assessment was similar between the sequential and parallel protocols (8.7 [IQR, 6-9] minutes vs 10.1 [IQR, 7-11] minutes, respectively; P = .30). A sequential POCUS-assisted protocol posed less workload to POCUS operators than the parallel protocol.


Stimulation of glycogenolysis in hepatocytes by angiotensin II may involve both calcium release and calcium influx.
The stimulation of [3H]glucose release (a measure of glycogenolysis) from isolated guinea pig hepatocytes by Ca-mobilizing agonists can be resolved into two phases. The initial transient phase is independent of extracellular Ca, and is probably a result of Ca released from an intracellular pool. The second phase occurs only in the presence of extracellular Ca, which suggests that Ca-influx is also involved in the mechanism of Ca-mobilization by these agents in the guinea pig hepatocyte.


Nitrogen induced DOC and heavy metals leaching: Effects of nitrogen forms, deposition loads and liming.
Atmospheric nitrogen (N) deposition is believed to accelerate dissolved organic carbon (DOC) production and could lead to increased heavy metal mobility into water resources. We sampled intact soil cores from the Isle of Skye with low background N deposition history and having Serpentine rock known for its higher heavy metal concentrations including zinc (Zn), copper (Cu), nickel (Ni) and lead (Pb). The effects of 16 (16kgN) and 32 kg N ha-1 year-1 (32kgN), and liming with 32kgN (32kgN+Lime) on soil solution chemistry and heavy metal mobilization were investigated over the 15-month study. Nitrogen in deposition load was added at five ammonium (NH4+) to nitrate (NO3-) ratios of 9:1, 5:1, 1:1, 1:5 and 1:9 along NO3-dominance. We found significant effects of load on Cu and NH4+/NO3- ratio on pH, DOC and Zn in soil solution. However, under lime and ratio experimental factors, liming significantly influenced pH, DOC, Cu and Pb, and NH4+/NO3- ratio pH, DOC, Ni and Zn whereas interactions between lime and ratio was significant for Ni and Cu. pH and DOC increased with N load, liming and NO3- dominance, and both correlated significantly positively. Liming under NH4+ dominance enhanced DOC production due to supply of base cations in lime. Mobilization of Cu, Ni and Pb was driven by DOC concentrations and, therefore, increased with load, liming and NO3- dominance in deposition. However, in contrast, low pH and high NH4+ dominance was associated with Zn mobilization in soil solution. On the contrary, despite of some patterns, heavy metals in soil HNO3 extracts were devoid of any load, lime and NH4+/NO3- ratio effects. Our study suggests that the effects of N load and forms in deposition on sites with high accumulated loads of metals need to be better quantified through soil solution partitioning models.


X-ray induced translocations in bone marrow cells of scid and wild type mice detected by fluorescence in situ hybridization using mouse chromosome specific DNA libraries.
Radiation induced chromosomal aberrations in bone marrow cells of scid and normal mice were studied at different sampling times. Fluorescence in situ hybridization (FISH) with DNA libraries specific for chromosomes 1, 11 and 13 was applied to identify the stable types of chromosomal aberrations in addition to the unstable ones. The results obtained confirm earlier observations on stem cell spermatogonia in that, contrary to the situation in normal mice, only very low levels of translocations could be recovered from scid mice at relatively long sampling times (3 weeks). However, studies at a 24 h sampling period demonstrated substantial induction of translocations in scid mice. This suggests enhanced elimination of translocation carrying cells in scid mice during successive cell proliferation, possibly via falling apart of the translocation at the original points of exchange or due to lethal damage at the translocation break points.


Morphological changes in the midgut of Aedes aegypti L. (Diptera: Culicidae) larvae following exposure to an Annona coriacea (Magnoliales: Annonaceae) extract.
Bioinsecticides are important in the control of disease vectors, but data regarding their physiological effects on target insects are incomplete. This study describes morphological changes that occur in the midgut of third instar Aedes aegypti L. (Diptera: Culicidae) following treatment with a methanolic extract of Annona coriacea (Magnoliales: Annonaceae). Dissected midguts were subdivided into anterior and posterior regions and analyzed by light and scanning electron microscopy. Insects exposed to the extract displayed intense, destructive cytoplasmic vacuolization in columnar and regenerative midgut cells. The apical surfaces of columnar cells exhibited cytoplasmic protrusions oriented toward the lumen, suggesting that these cells could be involved in apocrine secretory processes and/or apoptosis. We report that A. coriacea extracts induced morphological alterations in the midgut of A. aegypti midgut larvae, supporting the use of plant extracts for control of the dengue vector.


Study on injury effect of food additive citric acid on liver tissue in mice.
To investigate the damaging effect and action mechanism of the food additive citric acid (CA) on mouse liver, 40 healthy male Kunming mice were randomly divided into control group (0.9 % saline), low CA dose (120 mg/kg), middle dose (240 mg/kg) and high dose groups (480 mg/kg). All experimental mice have received peritoneal injection of the corresponding reagent each week for 3 weeks. After 7 days since the third injection, morphological changes were observed by light microscope; activities of T-SOD, glutathione peroxidase (GSH-Px), caspase-3, and contents of hydrogen peroxide (H2O2) and malonyldialdehyde (MDA) in the liver were evaluated using the corresponding assay kits; DNA fragmentation was assayed using agarose gel electrophoresis. Microscopical detection showed a series of hispathological changes in mouse livers treated with CA, such as indiscriminate liver cell cord, blood clot in central veins, and lymphocyte infiltrating. Biochemical examination suggested the gradually but moderately reduced T-SOD activity and elevated H2O2 level with the increase of CA dose (P > 0.05), and the gradually reduced GSH-Px activity and increased MDA content depending on graded doses with a significant difference (P < 0.05) between the high dose group and the control group. According to cell apoptosis assays, caspase-3 activity were significantly higher in all treatment groups than in the control (P < 0.05) in a dose-dependent manner. Contrasting to the control, characteristic DNA laddering was observed when injected with any of the three graded doses. It can be concluded that certain concentrations of CA cause oxidative damage of the liver by means of the decrease of antioxidative enzyme activities, thus resulting in MDA level elevation and DNA fragmentation inducing active caspase-3.


Exposure to high levels of oxygen in neonatal rats induce a decrease in hemoglobin levels.
Anemia of prematurity is common in extremely preterm neonates, and oxygen exposure may participate to anemia by inhibiting erythropoietin secretion. We aimed to determine whether hyperoxia exerts an independent role in the occurrence of the anemia of prematurity. Sprague-Dawley pups were exposed to 80% oxygen or room air from days 3 to 10 of life. Main outcome was the difference in hemoglobin and circulating erythropoietin levels in animals exposed to hyperoxia at 10 days of life. We performed a complete blood count analysis using fluorescent laser flow cytometry and measured circulating erythropoietin levels using ELISA. We found lower hemoglobin in the hyperoxia group, compared to the normoxia group, both in males (70 ± 3 versus 78 ± 2 g/l) and in females (71 ± 2 versus 81 ± 3 g/l) at 10 days of life. Reticulocyte count was not increased in the hyperoxia group. Circulating erythropoietin levels were lower at 10 days of life in the animals exposed to hyperoxia, both in males (33 ± 7 versus 73 ± 6 pg/ml) and in females (37 ± 5 versus 66 ± 3 pg/ml), but were similar at 28 days of life. Neonatal exposure to hyperoxia decreases hematopoiesis in rats. Mechanisms leading to anemia of prematurity are not well known and their study in humans is complicated due to multiple confounders. This study shows for the first time that exposure to high concentrations of oxygen in the neonatal period decreases hematopoiesis in rats, providing insight on the pathophysiological mechanisms of the anemia of prematurity. This research paves the way for future therapeutic developments aiming to reduce the burden of anemia of prematurity and the necessity of red blood cell transfusions in extremely preterm neonates.


X-ray structure of the Rhodobacter sphaeroides reaction center with an M197 Phe→His substitution clarifies the properties of the mutant complex.
The first steps of the global process of photosynthesis take place in specialized membrane pigment-protein complexes called photosynthetic reaction centers (RCs). The RC of the photosynthetic purple bacterium Rhodobacter sphaeroides, a relatively simple analog of the more complexly organized photosystem II in plants, algae and cyanobacteria, serves as a convenient model for studying pigment-protein interactions that affect photochemical processes. In bacterial RCs the bacteriochlorophyll (BChl) dimer P serves as the primary electron donor, and its redox potential is a critical factor in the efficient functioning of the RC. It has previously been shown that the replacement of Phe M197 by His strongly affects the oxidation potential of P (E m P/P+), increasing its value by 125 mV, as well as increasing the thermal stability of RC and its stability in response to external pressure. The crystal structures of F(M197)H RC at high resolution obtained using various techniques presented in this report clarify the optical and electrochemical properties of the primary electron donor and the increased resistance of the mutant complex to denaturation. The electron-density maps are consistent with the donation of a hydrogen bond from the imidazole group of His M197 to the C2-acetyl carbonyl group of BChl PB. The formation of this hydrogen bond leads to a considerable out-of-plane rotation of the acetyl carbonyl group and results in a 1.2 Å shift of the O atom of this group relative to the wild-type structure. Besides, the distance between BChl PA and PB in the area of pyrrole ring I was found to be increased by up to 0.17 Å. These structural changes are discussed in association with the spectral properties of BChl dimer P. The electron-density maps strongly suggest that the imidazole group of His M197 accepts another hydrogen bond from the nearest water molecule, which in turn appears to form two more hydrogen bonds to Asn M195 and Asp L155. As a result of the F(M197)H mutation, BChl PB finds itself connected to the extensive hydrogen-bonding network that pre-existed in wild-type RC. Dissimilarities in the two hydrogen-bonding networks near the M197 and L168 sites may account for the different changes of the E m P/P+ in F(M197)H and H(L168)F RCs. The involvement of His M197 in the hydrogen-bonding network also appears to be related to stabilization of the F(M197)H RC structure. Analysis of the experimental data presented here and of the data available in the literature points to the fact that the hydrogen-bonding networks in the vicinity of BChl dimer P may play an important role in fine-tuning the redox properties of the primary electron donor.


Interocular differences in higher-order aberrations on binocular visual performance.
To analyze the influence of higher-order aberrations on binocular visual performance under mesopic conditions. We measured aberrations in both eyes of 35 emmetropic observers with a Wasca aberrometer. Binocular visual performance was checked with both binocular summation for contrast sensitivity function and a parameter that characterizes stereopsis (maximum disparity). Binocular summation and maximum disparity significantly decrease with increasing interocular differences in higher-order aberrations (total, coma, and spherical aberration). At least some aspects of binocular visual performance are less effective for large interocular differences in higher-order eye aberrations.


Integrated palliative care: triggers for referral to palliative care in ICU patients.
Palliative care within intensive care units (ICU) benefits decision-making, symptom control, and end-of-life care. It has been shown to reduce the length of ICU stay and the use of non-beneficial and unwanted life-sustaining therapies. However, it is often initiated late or not at all. There is increasing evidence to support screening ICU patients using palliative care referral criteria or "triggers". The aim of the project was to assess the need for palliative care referral during ICU admission using "trigger" tools. Electronic record review of cancer patients who died in or within 30 days of discharge from oncology ICU, between 2016 and 2018. Patients referred to palliative care before or during ICU admission were identified. Three sets of palliative care referral "triggers" were applied: one that is being tested locally and two internationally derived tools. The proportion of patients who met any of these triggers during their final ICU admission was calculated. Records of 149 patients were reviewed: median age 65 (range 20-83). Most admissions (89%) were unplanned, with the most common diagnoses being haemato-oncology (31%) and gastrointestinal (16%) cancers. Most (73%) were unknown to palliative care pre-ICU admission; 44% were referred between admission and death. The median time from referral to death was 0 day (range 0-19). On ICU admission, 97-99% warranted referral to palliative care using locally and internationally derived triggers. All "trigger" tools identified a high proportion of patients who may have warranted a palliative care referral either before or during admission to ICU. The routine use of trigger tools could help streamline referral pathways and underpin the development of an effective consultative model of palliative care within the ICU setting to enhance decision-making about appropriate treatment and patient-centred care.


Herpes simplex virus type 2 incidence and associated risk factors among female sex workers in a high HIV-prevalence area of China.
Herpes simplex virus type 2 (HSV-2) can contribute to the spread of HIV. From March 2006 to November 2009, female sex workers (FSWs) in Yunnan, China were recruited into an open cohort study to determine incidence and risk factors for HSV-2 acquisition. Participants were interviewed and tested for HSV-2 and other sexually transmitted infections (STIs) every six months. A multivariate Cox proportional hazards regression model with time-dependent variables was used to measure associations with HSV-2 acquisition. In 3.5 years, 83 incident cases of HSV-2 infection were diagnosed, yielding an overall incidence of 21.9 per 100 person years (PY) (95% confidence interval [CI], 17.8-26.3). Working in higher risk commercial sex venues, current Neisseria gonorrhoeae infection, age of sexual debut <18 years and lack of a regular sex partner were independent factors associated with HSV-2 acquisition. The high incidence of HSV-2 suggests that prevention methods for HIV/STI control are urgently needed.


Youth engagement in mental health research: A systematic review.
Patient engagement in youth mental health research has the potential to inform research on the interventions, services and policies that will benefit youth. At present, there is little evidence to guide mental health researchers on youth engagement. This systematic review aims to describe the impacts of youth engagement on mental health research and to summarize youth engagement in mental health research. We searched the following databases: MEDLINE, EMBASE and PsycINFO, using a combination of subject headings, keywords and synonyms for the concepts 'patient engagement', 'youth' and 'mental health'. Articles that described engaging youth in mental health research were included. Two reviewers performed the study selection. Study characteristics, research activities performed by youth, impacts of youth engagement, challenges, and facilitators to engagement and recommendations for youth engagement described by authors were extracted. Quality appraisal involved determining the level of engagement of youth and the stage(s) of research where youth were involved. The database search returned 2836 citations, 151 full-text articles were screened and 16 articles, representing 14 studies, were selected for inclusion. Youth were involved at nearly all stages of the research cycle, in either advisory or co-production roles. Youth engagement impacts included enhancing relevant research findings, data collection and analysis and dissemination to academic and stakeholder audiences. Both youth and academic researchers reported personal development across many domains. One negative impact reported was the increase in funding and resources needed for engagement. We produced a list of 35 recommendations under the headings of training, youth researcher composition, strategy, expectations, relationships, meeting approaches and engagement conditions. This study provides an understanding of the impacts and recommendations of youth engagement in mental health research. The findings from this study may encourage researchers to engage youth in their mental health research and support youth engagement in funding applications. We consulted three youths with experience being engaged in mental health research about the review findings and the discussion. One youth designed a visual representation of the results and provided feedback on the manuscript. All youth's input informed the way the findings were presented and the focus of the discussion.


DNA binding properties of the ecdysteroid receptor in the salivary gland of the female ixodid tick, Amblyomma hebraeum.
Salivary gland degeneration in the female tick, Amblyomma hebraeum Koch (Acari: Ixodidae) is controlled by an ecdysteroid hormone. In an earlier study (Mao, H., McBlain, W.A., Kaufman, W.R., 1995. Some properties of the ecdysteroid receptor in the salivary gland of the ixodid tick, Amblyomma hebraeum. Gen. Comp. Endocrinol. 99, 340-348), we demonstrated that a protein component of a salivary gland extract binds to ponasterone A (Pon A) with high affinity (Kd-1 nM), suggesting a tick ecdysteroid receptor (EcR). In this study, the Pon A binding protein bound to calf thymus DNA; this binding could be dissociated by Drosophila hsp27 EcRE. The binding protein shifted the [32P]hsp27 EcRE band on a gel mobility shift assay; formation of the complex with hsp27 EcRE required KCl (optimal concentration was approximately 75 mM). A number of physiologically effective ecdysteroids enhanced the binding with the following order of potency: Pon A > Mur A > Mak A > 20E > ecdysone, whereas vertebrate steroids (estradiol, cholesterol, corticosterone, progesterone, testosterone) had no such effect. Using monoclonal antibodies against Drosophila EcR and USP, we found that AG 10.2 recognized three bands (90.5, 87.3 and 84 kDa for EcR) and AB11 recognized at least two major bands (50.3 and 47.1 kDa for USP) in the salivary gland extract by western blot analysis. In addition, AB11 supershifted the tick EcR-hsp27 EcRE band on a gel mobility shift assay, indicating that the tick EcR heterodimerized with a USP-like protein for DNA binding. Furthermore, selective mutations to the 15-basepair palindrome of hsp27 EcRE at positions-5, + 2, or adding a base to the spacer, resulted in considerably reduced affinity to the tick EcR/USP. We thus propose a sequence similarity of EcREs between A. hebraeum and its insect counterpart.


Stiffness and shape of the ACL graft affects tunnel enlargement and graft wear.
Tunnel enlargement and graft rupture are common complications associated with ACL reconstruction (ACLR). This study aims to explore how variations in graft stiffness and shape affect the strain energy density (SED) around bone tunnel entrances and stress on the graft and subsequently influencing the level of tunnel enlargement and graft wear. Finite element ACLR models were developed using different graft stiffnesses (323 N/mm, 545 N/mm and 776 N/mm) and shapes (circular and elliptical). The models were subjected to a combined loading of 103 N anterior tibial load, 7.5 Nm internal tibial moment, and 6.9 Nm valgus tibial moment at joint flexion of 30°. SED at tunnel entrances and stresses on the graft was recorded and compared among the different models. Increasing the graft stiffness resulted in greater stress on the graft (17.2, 24.4 and 31.7 MPa for graft stiffnesses of 323 N/mm, 545 N/mm and 776 N/mm), but had little effect on the SED reduction around the tunnel entrances. Changing the cross section of the graft from circular to elliptical caused an additional reduction in SED (56.8 vs 2.8 kJ/m3) at the posterior zone of the femoral tunnel entrance and increased the stress on the graft (31.7 MPa vs 38.9 MPa). This study recommends using ACL grafts with lower stiffness and a circular cross section to reduce tunnel enlargement and graft wear following ACLR.


"Inside Disc Out" Discectomy for the Treatment of Discogenic Lumbar Spinal Canal Stenosis under the Intervertebral Foramen Endoscope.
Conventional posterior-approach decompression surgeries have a higher risk of nerve root injury and dura laceration. We explore the therapeutic strategy and effect of "inside disc out" discectomy under intervertebral foramen endoscope technique for discogenic lumbar spinal canal stenosis (DLSS) treatment. Twenty-nine patients with DLSS in the responsible segment were treated with "inside disc out" discectomy under intervertebral foramen endoscope technique between October 2017 to October 2019. Lower limb and back pain were recorded before operation, and visual analogue scale (VAS) score and Oswestry disability index (ODI) were recorded for lower limb and back pain at 1, 3, 6, and 12 months postoperatively. The postoperative effects were evaluated using the modified MacNab method for all the patients. All 29 patients successfully completed the operation. The operation time was 75-120 min, with an average of 90 ± 17 min. Postoperative lumbar CT examinations of all the patients showed full decompression of the spinal cord with no residual pressure. The average follow-up time for all the patients was 13 ± 3.5 months (12-18 months). The VAS score for lower back and lower limb pain was 7.52 ± 1.25 before the operation, and 1.80 ± 0.63, 1.33 ± 0.88, 1.07 ± 0.89, and 0.81 ± 0.51 at 1, 3, 6, and 12 months after the surgery, respectively. The Oswestry dysfunction index was 59.43 ± 10.04 before surgery and 29.67 ± 10.35, 21.13 ± 9.32, 14.52 ± 5.98, and 9.84 ± 4.68 at 1, 3, 6, and 12 months after the surgery, respectively. The VAS score and ODI index of low back and lower limb pain at different time points after the surgery were significantly improved compared to those before the surgery (P < 0.01). The effect of the modified MacNab was excellent in 26 patients, good in two patients, and fair in one patient. The excellent and good rates were 91.4%. Among them, one patient had symptoms of hyperesthesia in the anterior aspect of the thigh and decreased quadriceps muscle strength after lumbar 4/5 segment endoscopic surgery. After symptomatic and conservative treatment, the symptoms disappeared 4 weeks postoperatively, and there were no other serious surgical complications. Following the "inside disc out" discectomy under intervertebral foramen endoscope protocols, the risk of nerve injury can greatly be reduced, with good postoperative efficacy. Overall, the procedure is safe and feasible for DLSS treatment.


Barefoot walking changed relative timing during the support phase but not ground reaction forces in children when compared to different footwear conditions.
There is a paucity of available biomechanical kinetic data comparing shod and barefoot conditions in children. Do children wearing footwear have comparable gait velocity, ground reaction forces (GRF), spatiotemporal parameters, propulsive and braking impulses when compared to children walking barefoot? Seventy-five children were divided into four groups: Group 1 females aged 4-9 years old (n = 29). Group 2 females aged 3-5 years old (n = 16). Group 3 males aged 6-9 years old (n = 13). Group 4 males aged 4-8 years old (n = 17). Children walked at a self-selected pace over a walkway of force platforms. Each footwear and barefoot represented a separate condition. The order of conditions was randomized. A repeated-measures ANOVA was performed to investigate the effects of the footwear type on gait parameters in each group. Multiple comparisons with Bonferroni corrections were conducted when appropriate. There were no statistical differences in velocity or in vertical and anteroposterior GRF across conditions for all groups. There was a significant effect of the footwear worn on time to loading response peak (p = 0.008), time to midstance force (p = 0.006), and time to propulsive peak (p < 0.001). For Group 3, there was a significant effect of the footwear worn on time to braking peak (p < 0.001) and time to propulsive peak (p < 0.001). Regarding impulses for Group 1, there was a significant effect of the footwear worn on the loading response impulse (p = 0.016) and terminal stance and pre-swing impulse (p = 0.001). For Group 4, there was a significant effect of the footwear worn on the loading response impulse (p = 0.028). There is no influence of the evaluated children's footwear on gait velocity or GRF.


Punctate inner choroidopathy.
Ten moderately myopic women had blurred vision, light flashes, or paracentral scotomas associated with small yellow-white lesions of the inner choroid and pigment epithelium. Most lesions had an overlying serous detachment, were hyperfluorescent, and leaked fluorescein during the acute phase. The lesions healed into atrophic scars and became progressively more pigmented with time. Subretinal neovascular membranes later developed from scars in six patients. Vision was usually only minimally affected unless the lesions were subfoveal or unless choroidal neovascular membranes subsequently occurred. Extensive laboratory studies were noncontributory.


Baseline sensitivity and action mechanism of the sterol demethylation inhibitor flusilazole to Valsa mali.
The apple Valsa canker caused by Valsa mali is a devastating branch disease that has seriously threatened the development of the apple industry worldwide. In current study, a total of 115 V. mali strains collected from different apple orchards in Shaanxi Province of China during 2016 and 2017 were tested for their sensitivity to flusilazole. The average EC50 (effective concentrations causing 50% mycelial growth inhibition) value of all tested strains for flusilazole was 0.0892 (±0.0036) μg/mL and the frequency distribution of the EC50 values was unimodal. Flusilazole exhibited both excellent protective and curative activity on detached apple branches, which was significantly better than the commonly used fungicide thiophanate-methyl. After flusilazole treatment, mycelia twisted with offshoot of top increased, the V. mali strains lost the ability of fruiting body production, and cell membrane permeability of the mycelia increased while ergosterol content and pectinase activity decreased. The expression of pectinase genes involved in virulence down-regulated after flusilazole treatment. This study is the first report on the baseline sensitivity of V. mali to flusilazole. These results indicated that flusilazole has a great potential to play an important role in the management of Valsa canker.


Isolation of quinupristin/dalfopristin-resistant Streptococcus agalactiae from asymptomatic Korean women.
Seven Streptococcus agalactiae isolates were obtained from the vagina of 80 asymptomatic women. Three of these isolates showed multi-drug resistant (MDR) phenotypes: two isolates were resistant to clarithromycin, clindamycin, erythromycin, and tetracycline; and one isolate was resistant to clarithromycin, clindamycin, erythromycin, tetracycline, and quinupristin/dalfopristin. There was no clonal relationship among the MDR isolates. This is the first report of quinupristin/dalfopristin-resistant S. agalactiae.


Inhibition of malodorous gas formation by oral bacteria with cetylpyridinium and zinc chloride.
The antimicrobial efficacy of zinc- (ZnCl2) and cetylpyridinium-chloride (CPC) and their inhibition capacity on volatile sulfur compound (VSC) production by oral bacterial strains were investigated. Minimum inhibitory concentrations (MIC) and growth curves were determined for ZnCl2, CPC, and CPC with ZnCl2 solutions against eight oral microorganisms (Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, Tannerella forsythia, Staphylococcus aureus and Streptococcus mutans) known to be involved in the pathophysiology of both halitosis and periodontal disease. Gas chromatography was applied to measure VSCs (H2S, CH3SH, (CH3)2S) production levels of each strains following exposure to the solutions. ZnCl2 and CPC effectively inhibited growth of all eight strains. ZnCl2 was generally more effective than CPC in suppressing bacterial growth excluding A. actinomycetemcomitans, P. intermedia, and T. forsythia. Synergism between CPC and ZnCl2 was shown in A. actinomycetemcomitans. The MIC for CPC was significantly lower than ZnCl2. VSC production was detected in five bacterial strains (A. actinomycetemcomitans, F. nucleatum, P. gingivalis, T. denticola, and T. forsythia). Each bacterial strain showed unique VSCs production profiles. H2S was produced by F. nucleatum, P. gingivalis, and T. denticola, CH3SH by all five strains and (CH3)2S by A. actinomycetemcomitans, F. nucleatum, P. gingivalis, and T. denticola. Production of CH3SH, the most malodorous component among the three major VSCs from mouth air was evident in F. nucleatum and T. forsythia. Both ZnCl2 and CPC effectively inhibit bacterial growth causative of halitosis and periodontal disease, resulting in a direct decrease of bacterial VSCs production.


Persistence of HIV-1 Env-Specific Plasmablast Lineages in Plasma Cells after Vaccination in Humans.
Induction of persistent HIV-1 Envelope (Env) specific antibody (Ab) is a primary goal of HIV vaccine strategies; however, it is unclear whether HIV Env immunization in humans induces bone marrow plasma cells, the presumed source of long-lived systemic Ab. To define the features of Env-specific plasma cells after vaccination, samples were obtained from HVTN 105, a phase I trial testing the same gp120 protein immunogen, AIDSVAX B/E, used in RV144, along with a DNA immunogen in various prime and boost strategies. Boosting regimens that included AIDSVAX B/E induced robust peripheral blood plasmablast responses. The Env-specific immunoglobulin repertoire of the plasmablasts is dominated by VH1 gene usage and targeting of the V3 region. Numerous plasmablast-derived immunoglobulin lineages persisted in the bone marrow >8 months after immunization, including in the CD138+ long-lived plasma cell compartment. These findings identify a cellular linkage for the development of sustained Env-specific Abs following vaccination in humans.


High molecular weight proteins in cardiac and skeletal muscle junctional sarcoplasmic reticulum vesicles bind calmodulin, are phosphorylated, and are degraded by Ca2+-activated protease.
A unique set of high molecular weight proteins was identified in junctional sarcoplasmic reticulum (SR) vesicles isolated from both cardiac muscle and skeletal muscle. These high Mr proteins were not present in free SR vesicles isolated from either tissue, nor were they observed in purified sarcolemmal fractions. The junctional SR high Mr proteins migrated as doublets in sodium dodecyl sulfate-polyacrylamide gels and exhibited apparent Mr values between 290,000 and 350,000. The high Mr proteins bound calmodulin; they were the principal proteins labeled in the cardiac and skeletal muscle SR subfractions by azido-125I-calmodulin. The high Mr proteins were also substrates for an endogenous Ca2+-calmodulin-dependent protein kinase activity, as well as exogenously added catalytic subunit of cAMP-dependent protein kinase. In addition, the junctional SR high Mr proteins were the major SR proteins degraded by a Ca2+-activated protease purified from smooth muscle. Control experiments verified the separation of junctional SR vesicles and free SR vesicles from both muscle types. Junctional SR vesicles were enriched in calsequestrin, and they exhibited Ca2+ uptake which was stimulated up to 10-fold by either ryanodine or ruthenium red. Free SR vesicles were deficient in calsequestrin and were insensitive to these two agents. Localization of the cardiac and skeletal muscle high Mr proteins to the junctional SR, coupled with demonstration of their nearly identical biochemical properties, suggests that the proteins are homologous and are likely to have similar functions in both types of striated muscle.


Talk Louder So I Can See You.
How does one sense influence the processing of another? In this issue of Neuron, Ibrahim et al. (2016) demonstrate that presence of sound sharpens neural tuning in the primary visual cortex via activation of direct inputs from the primary auditory cortex.


The focal trough of the Autopan panoramic dental x-ray machine.
The focal trough of the Autopan machine was evaluated with a multiline test object. The width of the focal trough varied from 5.5 mm anteriorly to about 23 mm in the midramus area with 1.7 line pairs per millimeter of resolution. The focal trough covers most tooth position areas. The machine is capable of producing clinically acceptable radiographs in most clinic populations.


Comparison of phenolic composition and sensory quality among pear beverages made using Saccharomyces cerevisiae and Torulaspora delbrueckii.
The effects of Saccharomyces cerevisiae and Torulaspora delbrueckii on phenolic composition and sensory quality were characterized in the production of alcoholic beverages from selected pear cultivars with diverse biochemical characteristics. The fermentation process generally affected the phenolic composition by increasing the contents of hydroxycinnamic acids and flavan-3-ols and reducing the levels of hydroxybenzoic acids, procyanidins, and flavonols. Although the phenolic compositions and sensory properties of pear beverages depended primarily on pear cultivar selection, the applied yeast strains also played important roles in beverage quality. Fermentation with T. delbrueckii resulted in higher caffeoylquinic acid and quercetin-3-O-glucoside contents, higher rated intensities of 'cooked pear' and 'floral' odors and a sweeter taste than fermentation with S. cerevisiae. Moreover, higher concentrations of hydroxybenzoic acids, hydroxycinnamic acids, and flavonols correlated closely with astringency perception. Applying T. delbrueckii strains and breeding novel pear cultivars are important approaches to produce fermented beverages of high quality.


Reduced-force closed trocar entry technique: analysis of trocar insertion force using a mechanical force gauge.
Trocar insertion injury has a high morbidity, mortality, and cost. The purpose of this study was to compare standard trocar entry with our reduced-force closed trocar entry technique by measuring trocar insertion force using a mechanical force gauge. In the operating room, the force gauge was inserted into a sterile glove and connected to the proximal portion of the trocar to measure insertion force. Through one incision, we used a standard closed trocar entry, while through the other incision, we used our reduced-force closed trocar entry technique. After making the skin incision and before trocar entry, we spread and dilated the skin, subcutaneous tissue, fascia, and muscle with a hemostat. Twenty-five patients entered the trial and none were excluded. Median trocar insertion force was 3.3lb (range, 1.6 to 5.4) with our reduced-force trocar entry technique versus 6.5lb (range, 2.0 to 14.0) with the standard trocar entry (P=.001). No complications occurred with the reduced-force trocar entry technique. Our reduced-force trocar entry technique decreases trocar insertion force by 50%, requires no additional instruments or cost and is fast and safe. Reduced-entry force pressure may decrease the risk of trocar insertion injury.


Peroxynitrite decreases rabbit tissue factor activity in vitro.
Tissue factor (TF) is a primary initiator of physiological coagulation in vivo. Peroxynitrite (OONO(-)), a molecule formed from nitric oxide (NO) and superoxide (O(2). (-)), decreases human TF activity in vitro. Coagulopathy has been associated with hepatoenteric ischemia-reperfusion known to involve formation of OONO(-). Further, circulating TF activity decreases in rabbits after hepatoenteric ischemia-reperfusion. We hypothesized that exposure of rabbit TF to OONO(-) would result in a decrease in activity. OONO(-) generation was performed with 3-morpholinosydnonimine (SIN-1), a molecule that produces both nitric oxide and superoxide. Rabbit brain TF was incubated at 37 degrees C for 90 min with 1) 0 mM SIN-1, 2) 5 mM SIN-1, 3) 5 mM SIN-1 and 2000 U/mL recombinant human superoxide dismutase (hSOD1), or 4) 2000 U/mL hSOD1 (n = 8 per condition). TF activity was assessed by addition of TF samples to human plasma and measuring clot formation kinetics with a thrombelastograph(R). TF exposure to SIN-1 resulted in a 48% decrease in activity that was significantly different from the other three conditions (P < 0.001). There were no significant differences between the other conditions. We conclude that rabbit TF is inhibited by OONO(-), and further investigation to determine the role of OONO(-) in coagulopathies associated with hepatoenteric ischemia-reperfusion is warranted. Tissue factor (TF) initiates physiological coagulation in vivo. Hepatoenteric ischemia-reperfusion injury is associated with peroxynitrite (OONO(-)) formation, coagulopathy and decreased TF activity in rabbits. We determined that OONO(-) decreased rabbit TF activity in vitro via thrombelastography(R).


Thrombotic Microangiopathy as a Cause of Chronic Kidney Transplant Dysfunction: Case Report Demonstrating Successful Treatment with Eculizumab.
Atypical hemolytic uremic syndrome is a rare disease associated with genetic or acquired defects in complement regulation which frequently leads to renal failure. Disease often recurs early after kidney transplantation, leading to a rapid irreversible loss of function. Extrarenal features, such as hemolysis and thrombocytopenia, may not always occur, and diagnosis is made by demonstrating the classic features of thrombotic microangiopathy on renal biopsy. Eculizumab, a terminal complement inhibitor, has been used successfully to treat fulminant early recurrent disease after transplantation. We describe a case of disease recurrence presenting in the second year after transplantation with a gradual decline in function and the first report of eculizumab treatment for chronic thrombotic microangiopathy in a transplanted kidney. The resultant diagnostic challenges and successful response to eculizumab in this setting are discussed.


State and community-based efforts to foster interoperability.
The MidSouth eHealth Alliance is developing a comprehensive health information infrastructure supporting providers in three Tennessee counties. Success in the alliance's first year is the result of sustained leadership, a systematic assessment of regional needs and capabilities, a flexible technical architecture, and a critical review of best practices from four different data exchange models already operating in other states. Long-term evolution to a truly interoperable health information infrastructure will depend on the extent to which the alliance demonstrates value to consumers and practitioners.


Effect of topical dexamethasone and ciprofloxacin on bacterial flora of healthy conjunctiva.
To investigate the effects of topical dexamethasone and ciprofloxacin, alone and in combination, on the colony counts of conjunctival bacterial flora of healthy subjects. A total of 100 healthy subjects were randomly divided into four groups, consisting of 25 subjects each. Group 1 was treated with dexamethasone phosphate 0.1% (Maxidex). Group 2 was treated with ciprofloxacin 0.3% (Ciloxan) and Group 3 with a combination of these drugs. Group 4 received artificial tear solution (Tears Naturale) and served as control. The drops were administered one drop every 1 min. A pretreatment culture and recultures at 30, 90, and 180 min after application of final drops were performed on all subjects. The bacterial growth was evaluated in a quantitative manner. All cultures were performed in a double-masked fashion. ANOVA test was used for statistical analyses. While there was no significant difference among mean number of pretreatment colonies between the groups (P=0.85); the differences at 30, 90, and 180 min were statistically significant (P<0.001). During the study there was no statistically significant change in colony counts in Groups 1 and 4 (P=0.66 and 0.55, respectively). The colony count numbers decreased significantly at 30 and 90 min in Group 2 (P<0.001 and P=0.004) and at 30 min in Group 3 (P=0.002). Topically applied dexamethasone did not cause a significant change in colony counts of the healthy conjunctiva. Both ciprofloxacin and a combination of ciprofloxacin and dexamethasone were effective in the reduction of bacterial ocular flora.


Effects of gastroesophageal reflux on esophageal motility.
Esophageal characteristics during swallowing in individuals with reflux are not well known. This study aimed to compare manometric esophageal characteristics between a group of individuals with gastroesophageal reflux and a group without these symptoms. A stationary esophageal manometry and a questionnaire of gastrointestinal symptoms were performed on 41 individuals, of whom 13 (31.7%) complained of gastroesophageal reflux. The following data were obtained in cases of non-reflux vs. reflux: mean wave amplitude, 53.4 +/- 17.9 mm Hg vs. 48.6 +/- 11.8 mm Hg; similar mean upstroke; and lower esophageal sphincter pressure of 16.7 +/- 6.4 mm Hg vs. 17.9 +/- 4.9 mm Hg (p = 0.5). The relaxing degree and duration were similar. In the analysis according to the severity of the symptoms, we verified the following differences between cases of slight and severe reflux: amplitude in proximal esophagus, 40.75 +/- 13.1 mm Hg sec vs. 23.0 +/- 9.2 mm Hg sec (p = 0.02); mean average upstroke, 36.6 +/- 8.2 mm Hg sec vs. 24.8 +/- 7.3 mm Hg sec (p = 0.02); mean maximum upstroke, 61.4 +/- 10.4 mm Hg sec vs. 47.0 +/- 12.4mm Hg sec (p = 0.04); and relaxing duration, 5.36 +/- 2.0 sec vs. 8.76 +/- 1.6 sec (p = 0.01). 1. No differences in the manometric characteristics of the esophagus were found between individuals with and without reflux. 2. The wave amplitude and the upstroke were significantly higher in the proximal esophagus of patients with less severe complaints. 3. The mean and maximum upstroke of the esophageal wave were lower in individuals with severe reflux. 4. The relaxation duration was higher in patients with severe complaints.


Flow-mediated vasodilatation of the brachial artery in children with chronic kidney disease.
We sought to determine flow-mediated vasodilatation (FMD) of the brachial artery and to assess the relationship of FMD with multiple demographic, clinical and biochemical parameters and cardiac and vascular structure and function in children with chronic kidney disease (CKD) stages 2-4. Forty-three patients, aged 6-20 years, with CKD [mean glomerular filtration rate (GFR) 47 +/- 21 ml/min per 1.73 m2 body surface area, range 16-89 ml/min per 1.73 m2] and 34 healthy age-matched controls were included and studied cross-sectionally between 2001 and 2005. The peak FMD was similar in the CKD and control subjects (mean 6.3% vs 6.7%, P = 0.85). However, abnormally low FMD (< 1.1%) was found in ten (23%) children with CKD. Among children with CKD, those with low FMD were younger, shorter, lighter, and had lower body mass index (BMI) than children with normal FMD, but the difference reached statistical significance only for weight and BMI. Serum triglyceride levels were significantly lower in those with low FMD; otherwise, the two groups were similar with respect to multiple clinical and biochemical parameters. Cardiac and vascular structure was similar in children with normal and low FMD. In conclusion, children with CKD stage 2-4 appear to have increased prevalence of decreased FMD of the brachial artery. However, our study identified few significant factors associated with low FMD in children with CKD.


Risk Factors for Choroidal Detachment After Ahmed Valve Implantation in Glaucoma Patients.
To assess the incidence and risk factors related to choroidal detachment after glaucoma drainage device (Ahmed valve) implantation. Retrospective case-control study. A total of 188 eyes of 188 glaucoma patients were enrolled who underwent Ahmed valve implantation surgery. Patients were divided into 2 groups according to the presence or absence of choroidal detachment. The data were analyzed for factors associated with choroidal detachment. Separately, we divided eyes with choroidal detachment into 2 subgroups according to severity and conducted a subanalysis. In addition, we also analyzed the factors associated with chamber collapse. The incidence of choroidal detachment was 35.1% according to wide-field fundus photography and 16.9% according to 45-degree fundus photography. The current study showed that age, central corneal thickness, axial length, etiology of glaucoma, history of cataract or glaucoma, hypertension, diabetes, and severity of the visual field (MD) were different between the choroidal detachment and nonchoroidal detachment groups. A multivariate analysis showed significant differences in age (P = .035), etiology of glaucoma (pseudoexfoliation; PEX) (P = .028), lens status (pseudophakia) (P = .011), and hypertension (P = .011). The greater the intraocular pressure difference before and after surgery, the greater the size of the choroidal detachment. Chamber collapse risk was associated with only short axial length. The detection of choroidal detachment after Ahmed valve implantation can be increased according to the introduction of wide fundus photography. The risk of choroidal detachment is associated with the etiology of glaucoma (PEX), older age, pseudophakia (lens status), and hypertension.


Process of aerenchyma formation and reactive oxygen species induced by waterlogging in wheat seminal roots.
The development and regulation of aerenchyma in waterlogged conditions were studied in the seminal roots of wheat. Evans blue staining and the first cell death position indicated that the cortical cell death began at the root mid-cortex cells in flooding conditions. Continuous waterlogging treatment caused the spread of cell death from the mid-cortex to the neighboring cells and well-developed aerenchyma was formed after 72 h. Meanwhile, the formation of radial oxygen loss barrier was observed in the exodermis owing to the induction of Casparian bands and lignin deposition. Analysis of aerenchyma along the wheat root revealed that aerenchyma formed at 10 mm from the root tip, significantly increased toward the center of the roots, and decreased toward the basal region of the root. In situ detection of radial oxygen species (ROS) showed that ROS accumulation started in the mid-cortex cells, where cell death began indicating that cell death was probably accompanied by ROS production. Further waterlogging treatments resulted in the accumulation of ROS in the cortical cells, which were the zone for aerenchyma development. Accumulation and distribution of H₂O₂ at the subcellular level were revealed by ultracytochemical localization, which further verified the involvement of ROS in the cortical cell death process (i.e., aerenchyma formation). Furthermore, gene expression analysis indicated that ROS production might be the result of up-regulation of genes encoding for ROS-producing enzymes and the down-regulation of genes encoding for ROS-detoxifying enzymes. These results suggest that aerenchyma development in wheat roots starts in the mid-cortex cells and its formation is regulated by ROS.


Simulation of laser-induced tunnel ionization based on a curved waveguide.
The problem of tunneling ionization and the associated questions of how long it takes for an electron to tunnel through the barrier, and what the tunneling rate has fascinated scientists for almost a century. In strong field physics, tunnel ionization plays an important role, and accurate knowledge of the time-dependent tunnel rate is of paramount importance. The Keldysh theory and other more advanced related theories are often used, but their accuracy is still controversial. In previous work, we suggested using a curved waveguide as a quantum simulator to simulate the tunnel ionization process. Here we implemented for the first time such a curved waveguide and observed the simulated tunneling ionization process. We compare our results with the theory.


An update to "The cost-effectiveness of rotavirus vaccination: comparative analyses for five European countries and transferability in Europe".
A cost-effectiveness analysis of rotavirus vaccination in Belgium, England and Wales, Finland, France and the Netherlands published in 2009 was updated based on recent studies on rotavirus burden of disease and vaccine efficacy. All the qualitative conclusions in the previous study were found to remain valid. Vaccination remains cost-effective in Finland only when using plausible tender prices.


Concentrations of histamine in the hypothalamus of the rat: effect of extraction volume and interpretation of the effects of acutely-administered morphine.
The effect of varying the ratio of extraction volume to tissue weight (EVR) on the apparent concentration of histamine (HA) in the hypothalamus of the rat was examined. Increasing the weight of tissue (by pooling 1, 2 or 3 hypothalami), in a constant extraction volume, resulted in progressive decreases in apparent concentration of histamine in the hypothalamus. These concentrations were 642, 450 and 282 ng/g, respectively. Morphine (10 mg/kg, i.p.) significantly reduced the concentration of histamine in the hypothalamus. Expressed as percentages of the saline-control values (obtained for the extraction volume to tissue weight of 35.7, 57.2 and 118.4 ml/g), treatment with morphine resulted in 24, 17 and 11% reductions in the concentration of histamine in the hypothalamus, respectively. However, expressed in terms of ng/g, the reductions in histamine induced by morphine were 68, 75 and 69 ng/g, respectively. It is concluded that morphine may consistently affect a single pool of histamine. The possibility that de novo histamine is formed in the homogenate during the extraction process is discussed.


Porous titanium and Ti-35Nb alloy: effects on gene expression of osteoblastic cells derived from human alveolar bone.
Tests on titanium alloys that possess low elastic modulus, corrosion resistance and minimal potential toxicity are ongoing. This study aimed to evaluate the behavior of human osteoblastic cells cultured on dense and porous Titanium (Ti) samples comparing to dense and porous Ti-35 Niobium (Ti-35Nb) samples, using gene expression analysis. Scanning electronic microscopy confirmed surface porosity and pore interconnectivity and X-ray diffraction showed titanium beta-phase stabilization in Ti-35Nb alloy. There were no differences in expression of transforming growth factor-β, integrin-β1, alkaline phosphatase, osteopontin, macrophage colony stimulating factor, prostaglandin E synthase, and apolipoprotein E regarding the type of alloy, porosity and experimental period. The experimental period was a significant factor for the markers: bone sialoprotein II and interleukin 6, with expression increasing over time. Porosity diminished Runt-related transcription factor-2 (Runx-2) expression. Cells adhering to the Ti-35Nb alloy showed statistically similar expression to those adhering to commercially pure Ti grade II, for all the markers tested. In conclusion, the molecular mechanisms of interaction between human osteoblasts and the Ti-35Nb alloy follow the principal routes of osseointegration of commercially pure Ti grade II. Porosity impaired the route of transcription factor Runx-2.


Cytology in surgical practice.
Early cytological diagnosis in a patient presenting with acute abdominal pain averted laparotomy and expedited successful management. The place of cytological diagnosis in patient management is discussed.


WITHDRAWN: A synchronization method using heparin for the in vitro culture of Plasmodium falciparum.
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Tinzaparin sodium for thrombosis treatment and prevention during pregnancy.
This study was undertaken to assess the pharmacodynamic profile, safety, and efficacy of tinzaparin during pregnancy. Fifty-four pregnant women, 12 for treatment of thrombosis and 42 for thromboprophylaxis, received tinzaparin by once daily injection. Four-hour postdose anti-Xa results were analyzed by use of repeated measures statistical methods. One woman (3.4%) on the 175 anti-Xa U/kg dose and three women (20%) on the 50 anti-Xa U/kg dose required a dose increase during the initial dose titration phase to achieve target anti-Xa activity. No thrombotic events occurred. The 175 anti-Xa U/kg dose is appropriate for treatment and for high-risk thromboprophylaxis throughout pregnancy. In pregnant women at moderate risk of thrombosis, a higher tinzaparin dose is required than in the nonpregnant state and 75 anti-Xa U/kg appears to be appropriate. The majority of women do not need a dose increase with advancing gestation.


Structural Racism and Impact on Sickle Cell Disease: Sickle Cell Lives Matter.
Wealth begets health: the health care system in the United States is run by and benefits the groups that have traditionally held power. Systems of structural racism and health care disparities persist. Patients with sickle cell disease (SCD) remain particularly vulnerable to disparities. They suffer from stigmas, lack of well-trained providers, and from misalignment of their needs with the priorities of their health care teams. These critically important burdens may actually be worsening rather than improving mortality for individuals living with SCD. Changes must be made at the federal, state, and local levels in order to address these systems of inequity and save vulnerable lives.


Detection of multiple cardiac papillary fibroelastomas using transesophageal echocardiography.
Papillary fibroelastomas are rare, benign cardiac tumors that may be associated with embolization, angina, and sudden death. We report a case of multiple papillary fibroelastomas diagnosed during life by transesophageal echocardiography. Surgical resection during mitral valve replacement for rheumatic mitral stenosis prevented the development of any of the life-threatening complications sometimes associated with this tumor.


Erector Spinae Plane Block and Chronic Pain: An Updated Review and Possible Future Directions.
Chronic pain is a common, pervasive, and often disabling medical condition that affects millions of people worldwide. According to the Global Burden of Disease survey, painful chronic conditions are causing the largest numbers of years lived with disability worldwide. In America, more than one in five adults experiences chronic pain. Erector spinae plane block is a novel regional anesthesia technique used to provide analgesia with multiple possible uses and a relatively low learning curve and complication rate. Here, we review the erector spinae plane block rationale, mechanism of action and possible complications, and discuss its potential use for chronic pain with possible future directions for research.


Plasma proteomic profiling reveals KRT19 could be a potential biomarker in patients with anti-MDA5+ dermatomyositis.
To investigate the immune response-related protein profiling in plasma of patients with idiopathic inflammatory myopathies (IIMs), especially in anti-MDA5+ dermatomyositis (DM). A total of 166 IIM patients and 107 healthy controls (HCs) were enrolled in our study. Ninety-two plasma immune response-related proteins were detected by Olink proteomics in 36 IIM patients and 25 HCs. The expression of plasma KRT19 was validated in another 130 IIM patients, 82 HCs, and 55 other rheumatic diseases. A total of 46 differentially expressed proteins were detected, including 12 upregulated proteins and 34 downregulated proteins in IIM patients compared with HCs. Pathway analysis revealed lactoferrin danger signal response pathway, TLR4 signaling and tolerance, infection, and IL-10 signaling pathway were activated. The immune response-related protein profiling significantly altered in anti-MDA5+ DM patients, with LAMP3, HSD11B1, and KRT19 significantly increased, while SH2D1A, ITGA11, TRIM21, CD28, ITGB6, and HEXIM1 tremendously decreased. In addition, KRT19 was significantly increased in IIM patients, especially in anti-MDA5+ DM patients with the diagnostic value of a significant area under the ROC curve of 0.881. Immune response-related proteins are significantly altered in patients with anti-MDA5+ DM patients. KRT19 could be a potential biomarker for anti-MDA5+ DM patients. Key Points • What is already known on this topic? Anti-MDA5+ DM is a distinctive subtype of IIM. Plasma immune response-related proteins panel needs to be investigated. • What this study adds? Plasma protein profiling of immune response-related proteins significantly altered in patients with idiopathic inflammatory myopathies (IIM), especially in anti-MDA5+ DM patients. • How this study might affect research, practice, or policy? KRT19 could be a potential biomarker in patients with anti-MDA5+ dermatomyositis.


Antipsychotics and the Risk of Mortality or Cardiopulmonary Arrest in Hospitalized Adults.
Prior studies in outpatient and long-term care settings demonstrated increased risk for sudden death with typical and atypical antipsychotics. To date, no studies have investigated this association in a general hospitalized population. We sought to evaluate the risk of death or nonfatal cardiopulmonary arrest in hospitalized adults exposed to antipsychotics. Retrospective cohort study. Large academic medical center in Boston, Massachusetts. All hospitalizations between 2010 and 2016 were eligible for inclusion. We excluded those admitted directly to the intensive care unit (ICU), obstetric and gynecologic or psychiatric services, or with a diagnosis of a psychotic disorder. Typical and atypical antipsychotic administration, defined by pharmacy charges. The primary outcome was death or nonfatal cardiopulmonary arrest during hospitalization (composite). Of 150 948 hospitalizations in our cohort, there were 691 total events (515 deaths, 176 cardiopulmonary arrests). After controlling for comorbidities, ICU time, demographics, admission type, and other medication exposures, typical antipsychotics were associated with the primary outcome (hazard ratio [HR] = 1.6; 95% confidence interval [CI] = 1.1-2.4; P = .02), whereas atypical antipsychotics were not (HR = 1.1; 95% CI = .8-1.4; P = .5). When focusing on adults age 65 years and older, however, both typical and atypical antipsychotics were associated with increased risk of death or cardiopulmonary arrest (HR = 1.8; 95% CI = 1.1-2.9; and HR = 1.4; 95% CI = 1.1-2.0, respectively). Sensitivity analyses using a propensity score approach and a cohort of only patients with delirium both yielded similar results. In hospitalized adults, typical antipsychotics were associated with increased mortality or cardiopulmonary arrest, whereas atypical antipsychotics were only associated with increased risk among adults age 65 years and older. Providers should be thoughtful when prescribing antipsychotic medications, especially to older adults in settings where data regarding benefit are lacking. J Am Geriatr Soc 68:544-550, 2020.


Alcohol use, anxiety, and insomnia in older adults with generalized anxiety disorder.
To examine alcohol consumption among older primary care patients with generalized anxiety disorder (GAD); its relationship to demographic variables, insomnia, worry, and anxiety; and its moderating role on the anxiety-insomnia relationship. We expected alcohol use to be similar to previous reports, correlate with higher anxiety and insomnia, and worsen the anxiety-insomnia relationship. Baseline data from a randomized controlled trial. Michael E. DeBakey VA Medical Center and Baylor College of Medicine. 223 patients, 60 years and older, with GAD. Frequency of alcohol use, insomnia (Insomnia Severity Index), worry (Penn State Worry Questionnaire - Abbreviated, Generalized Anxiety Disorder Severity Scale), and anxiety (State-Trait Anxiety Inventory - Trait subscale, Structured Interview Guide for the Hamilton Anxiety Rating Scale [SIGH-A]). Most patients endorsed alcohol use, but frequency was low. Presence and frequency were greater than in previous reports of primary care samples. Alcohol use was associated with higher education, female gender, less severe insomnia, and lower worry (Generalized Anxiety Disorder Severity Scale) and anxiety (State-Trait Anxiety Inventory-Trait subscale; SIGH-A). Whites reported more drinks/week than African-Americans. More drinks/week were associated with higher education and lower anxiety (SIGH-A). Weaker relationships between worry/anxiety and insomnia occurred for those drinking. Drink frequency moderated the positive association between the Penn State Worry Questionnaire-Abbreviated and insomnia, which was lower with higher frequency of drinking. Older adults with GAD use alcohol at an increased rate, but mild to moderate drinkers do not experience sleep difficulties. A modest amount of alcohol may minimize the association between anxiety/worry and insomnia among this group.


Reductions in convictions for violent crime during opioid maintenance treatment: a longitudinal national cohort study.
Although opioid maintenance treatment (OMT) has been found to reduce crime, less is known about its associations with violent crime. This study investigates changes in violent crime convictions prior to, during, and after OMT, and examines the relationship between violent crime convictions prior to OMT with the risk of violent and non-violent crime convictions during treatment. The cohort comprised all who started OMT (n=3221) in Norway between 1997 and 2003. Treatment data were cross linked with the national Crime Registry. Convictions for violent crime 3 years prior to, during, and after treatment were studied. Violent crime rates were significantly reduced during OMT compared with before treatment, for both men and women. The rate of convictions for violent crime during OMT was halved amongst those who remained in treatment. The reduction was less pronounced for those who left treatment: for this group, the rate of violent convictions after OMT was higher than before treatment. The risk of convictions for violent and non-violent crime during OMT was highest for those with violent convictions prior to treatment. Violent crime is reduced during OMT. Screening for violent behaviour and violence risk assessment should be implemented in the treatment system.


Vegetation-Rainfall interactions reveal how climate variability and climate change alter spatial patterns of wildland fire probability on Big Island, Hawaii.
The area burned annually by wildland fire in Hawaii has increased fourfold in recent decades. The archipelago's novel fuel types and climatic heterogeneity pose significant challenges for fire risk assessment and fire management. Probability-based fire occurrence models using historical wildfire records provide a means to assess and attribute fire risk in regions of the world like Hawaii where investment in fire science is limited. This research used generalized additive models to 1) assess the relative contribution of vegetation, climate, and human-caused ignitions to the probability of fire in the northwest quadrant of Hawaii Island and 2) compare how landscape flammability varies due to interannual rainfall variability versus projected changes in mean annual rainfall (MAR) and temperature. Annual fire probability was highest for grasslands and peaked at drier conditions (0.04 at 450 mm MAR) when compared with shrublands (0.03 at 650 mm MAR) and forest (0.015 at 600 mm MAR). Excess rainfall the year prior to fire occurrence increased fire risk across grasslands, and thus overall fire probability, more so than drought the year that fire occurred. Drying and warming trends for the region under projected climate change increased maximum values of fire probability by as much as 375% and shifted areas of peak landscape flammability to higher elevation. Model predictions under future climate also indicate the largest changes in landscape flammability will happen by mid-Century. The influence of antecedent wet years on fire risk can improve near-term predictions of fire risk in Hawaii while climate projections indicate that fire management will need to be prioritized at upper elevations where high value natural resources are concentrated.


Development and evaluation of matrix and two layered sustained release suppositories of theophylline.
Theophylline loaded conventional suppositories, sustained release matrix suppositories and sustained release two layered suppositories were prepared using polyethylene glycol 4000 and eudragit RS-100 and their characteristics were evaluated both in-vitro and in-vivo. In comparison to conventional suppositories, the release of the drug from sustained release matrix suppositories was gradual and extended over a period of time. On the other hand two layered suppositories produced an initial quick release followed by extended release of the drug. The in-vivo results were found to correlate with the in-vitro results.


The problem of confounding social support and depressive symptoms: a brief report on a college sample.
The problem of confounding social support and depressive symptoms was addressed by examining the convergent and discriminant validity of interview and questionnaire measures of social support and depression using the multitrait-multimethod matrix approach. Participants were 40 late-adolescent college students with half the sample selected on the basis of mild to moderate scores on self-reported depressive symptoms. Measures of depression displayed excellent convergent and discriminant validity, and measures of objective features of social networks were found to have moderate convergent and discriminant validity. However, the subjective measures of satisfaction with social support used were found to have neither adequate convergent nor discriminant validity. Implications for the conceptualization and assessment of social support are highlighted.


Neonatal treatment of male rats with a gonadotropin-releasing hormone antagonist impairs ejaculation and fertility.
Pituitary-gonadal suppression of neonatal male rats with a gonadotropin-releasing hormone antagonist N-Ac-D-Nal(2)1,D-p-Cl-Phe2,D-Trp3,D-hArg(Et2)6,D-Ala10 -GnRH (RS 68439; Syntex; 2 mg/kg/day) during days 1-10 of life resulted in infertility of adult animals, when studied at the age of 90, 115 and 150 days. Numbers of fertile animals per rats tested at these ages were 1/10, 2/14 and 4/14, respectively, in the antagonist treated animals (vs. 8/10, 9/13 and 9/13 in controls; p less than 0.01-0.05). The numbers of mounts and intromissions were unaffected by the antagonist treatment, but none of the treated animals (n = 10) ejaculated in four subsequent behavior tests. However, if the vaginal smears were checked in a group of rats after caging the males separately with a normal female for 8 days before the behavior tests, each male had ejaculated but the females were not fertilized. When the neonatally GnRH antagonist-treated rats were followed in the long-term, fertility slowly recovered, and at the age of 220 and 350 days, the number of successful pregnancies was similar to that of age-matched controls. It is concluded that short-term neonatal pituitary-gonadal suppression with GnRH antagonist results in impaired ejaculation and infertility of adult male rats, but fertility slowly recovers within a year.


PIM: phase integrated method for normal mode analysis of biomolecules in a crystalline environment.
In this study, a normal mode analysis, named phase integrated method (PIM), is developed for computing modes of biomolecules in a crystalline environment. PIM can calculate low-frequency modes on one or a few asymmetric units (AUs) and generate exact modes of a whole unit cell according to space group symmetry, while the translational symmetry between unit cells is maintained via the periodic boundary condition. Therefore, the method can dramatically reduce computational cost in mode calculation in the presence of crystal symmetry. PIM also has an option to map modes onto a single AU to form an orthonormalized mode set, which can be directly applied to normal-mode-based thermal parameter refinement in X-ray crystallography. The performance of PIM was tested on all 65 space groups available in protein crystals (one protein for each space group) and on another set of 83 ultra-high-resolution X-ray structures. The results showed that considering space group symmetry in mode calculation is crucial for accurately describing vibrational motion in a crystalline environment. Moreover, the optimal inter-AU packing stiffness was found to be about 60% of that of intra-AU interactions (non-bonded interaction only).


Road traffic crashes among farm vehicle drivers in southern China: A cross-sectional survey.
The objective of this study was to identify the prevalence and potential risk factors of farm vehicle-related road traffic crashes among farm vehicle drivers in southern China. A cross-sectional study was used to interview 1,422 farm vehicle drivers in southern China. Farm vehicle-related road traffic crashes that occurred from December 2013 to November 2014 were investigated. Data on farm vehicle-related road traffic crashes and related factors were collected by face-to-face interviews. The prevalence of farm vehicle-related road traffic crashes among the investigated drivers was 7.2%. Farm vehicle-related road traffic crashes were significantly associated with self-reported vision problem (adjusted odds ratio [AOR] = 6.48, 95% confidence interval [CI], 3.86-10.87), self-reported sleep disorders (AOR = 10.03, 95% CI, 6.28-15.99), self-reported stress (AOR = 20.47, 95% CI, 9.96-42.08), reported history of crashes (AOR = 5.40, 95% CI, 3.47-8.42), reported history of drunk driving (AOR = 5.07, 95% CI, 2.97-8.65), and reported history of fatigued driving (AOR = 5.72, 95% CI, 3.73-8.78). The number of road traffic crashes was highest in the daytime and during harvest season. In over 96% of farm vehicle-related road traffic crashes, drivers were believed to be responsible for the crash. Major crash-causing factors included improper driving, careless driving, violating of traffic signals or signs, and being in the wrong lane. Findings of this study suggest that farm vehicle-related road traffic crashes have become a burgeoning public health problem in China. Programs need to be developed to prevent farm vehicle-related road traffic crashes in this emerging country.


catena-Poly[barium(II)-μ2-(dimethyl sulfoxide)-κ2 O:O-bis-(μ2-2,4,6-tri-nitro-phenolato-κ4 O 2,O 1:O 1,O 6)].
The asymmetric unit of the title barium coordination polymer, [Ba(C6H2N3O7)2(C2H6OS)] n , consists of a barium cation (site symmetry m) and a dimethyl sulfoxide (DMSO) ligand (point group symmetry m) and a 2,4,6-tri-nitro-phenolate anion located in general positions. The S atom and the methyl group of DMSO are disordered over two sets of sites. The DMSO ligand bridges a pair of BaII atoms resulting in a chain extending parallel to the a axis. The unique 2,4,6-tri-nitro-phenolate anion also bridges a pair of BaII ions via the phenolic oxygen atom, with each BaII being additionally bonded to an oxygen atom of an adjacent nitro group. The μ 2-monoatomic bridging binding mode of both types of ligands results in the formation of an infinite chain of face-sharing {BaO10} polyhedra flanked by the remaining parts of the 2,4,6-tri-nitro-phenolato and DMSO ligands. In the one-dimensional coordination polymer, parallel chains are inter-linked with the aid of C-H⋯O hydrogen bonds.


Effects of the 5-HT3 receptor antagonist, alosetron, in a rat model of somatic and visceral hyperalgesia.
Conflicting results exist regarding the role of 5-HT3 receptors in somatic and visceral nociceptive processing. We aimed to investigate the effects of the 5-HT3 receptor antagonist, alosetron, in a rat model of somatic and visceral hyperalgesia. Two injections (100 microl) of either pH 4.0 or 7.2 saline were given unilaterally in the gastrocnemius (GN) muscle. In all groups, the paw withdrawal thresholds (PWT) to von Frey filaments and the visceromotor responses (VMR) to colorectal distension (CRD) were recorded before the saline injections and 72 h, and 1 week after the second injection. Intrathecal (i.t.) (25 nmol) or intravenous (i.v.) (100 microg/kg/day) alosetron was given daily following the second injection and compared to either i.v. or i.t. saline (vehicle). There was a significant decrease in the mean PWT bilaterally in all groups following pH 4.0 injections (p<0.05). Intravenous alosetron resulted in a significant increase in the PWT bilaterally on days 2 and 3. Intrathecal alosetron resulted in significant increase in the PWT starting at day 3 and was significantly higher than baseline on days 4-7 (p<0.05). At CRD pressures 30 mmHg, the VMR of pH 4.0 injected rats was significantly increased at 72 h and 1 week (p<0.05). Both i.v. and i.t. alosetron treated rats failed to demonstrate any alteration in the VMR. Control rats (pH 7.2) failed to show any alteration in the VMR and were unaffected by alosetron. Both, systemically and centrally administered alosetron, reversed the mechanical somatic hypersensitivity and prevented the development of visceral hyperalgesia, suggesting a centrally mediated effect.