The health beliefs, dengue knowledge and control behaviors among internally displaced persons versus local residents in Kachin Special Region II, Myanmar.
Dengue fever (DF) is one of main public health problems along the China-Myanmar border, however, data about DF is still lacking in Kachin Special Region II (KSR2), Myanmar. To understand health beliefs in general, and knowledge and treatment-seeking and prevention behaviors related to DF among the neglected population, the study was carried out by using a combination of quantitative household questionnaire surveys (HHSs) and qualitative semi-structured in-depth interviews (SDIs). The HHS questionnaire was administered to a total of 258 household heads. The 215 (83.3%) HHS respondents believed in Christianity and Catholicism. However, the 141 (54.7%,) of the total respondents thought that people with evil practices might be punished by diseases. More respondents believed that too rainy weather and water were more related to disease in the internally displaced person (IDP) camp than the local community (P<0.01). Most of the HHS respondents had sound knowledge of dengue symptoms, causes, vectors, transmission and prevention. The 257 (99.6%) HHS respondents reported that their families went to the public health facilities first to seek treatment. The 210 (84.1%) respondents reported that they turned containers upside down within five days. The key informants (n = 18) identified that the appropriate knowledge and behaviors were attributable to formal school education and specific health education campaign during the outbreak response in 2017, and that Kachin people enjoy conversing with each other, neighbors talked about the dengue information they received. The study results indicated that Kachin people have a good knowledge and behaviors of dengue control. The actual situation of dengue is still not clear due to lacking data of laboratory test. In the context of resources shortage, more international assistance is still needed to promote local dengue control and prevention efforts.


EVOLUTION OF RESISTANCE IN CULEX PIPIENS: ALLELE REPLACEMENT AND CHANGING ENVIRONMENT.
Fixation of adaptive mutations in populations is often constrained by pleiotropic fitness costs. The evolutionary pathways that compensate such fitness disadvantages are either the occurrence of modifier genes or replacement of the adaptive allele by less costly ones. In this context, 23 years of evolution of insecticide resistance genes in the mosquito Culex pipiens from southern France are analyzed. The aim of this study is to answer the following points. Is there a fitness cost associated with these resistance genes in natural populations? Does evolution proceed through allele replacement or through selection of modifiers? And finally, how do environmental changes affect the evolution of resistance genes? Samples from the same transect, crossing the boundary between an insecticide-treated and a nontreated area, are analyzed. Clinal analyses indicate a variable fitness cost among the resistance genes and show that allele replacement has been the primary mechanism of resistance evolution in this area. It is also shown that replacement was probably due to environmental changes corresponding to modification in pesticide-treatment intensity.


Arterial stiffness in normal pregnancy at 11-13 weeks of gestation and risk of late-onset hypertensive disorders of pregnancy.
We evaluated the possible correlation between pulse wave analysis (PWA) parameters measured during the first trimester of pregnancy in normotensive, low-risk women, and the development of hypertensive disorders later in pregnancy. Our hypothesis was that a still asymptomatic increase in arterial stiffness may potentially precede the onset of overt hypertension in pregnancy and that PWA could detect it. The study population (n = 1648) was recruited at the time of prenatal screening for chromosomal abnormalities (11-12 weeks of gestation). The radial pressure waveform was obtained with an applanation tonometer (Sphygmocor, Atcor Medical, West Ryde, Australia) on pregnant women in recumbent position. Arterial stiffness was evaluated using arterial PWA. The aortic systolic pressure (aSp), aortic diastolic pressure, and aortic mean pressure, the aortic pulse pressure, the augmentation pressure, and the augmentation index were calculated. The main outcome measure was the development of hypertensive disorders later in pregnancy. The values of aSp (P < 0.0001), aortic diastolic pressure (P < 0.0001), aortic mean pressure (P < 0.0001), aortic pulse pressure (P = 0.0140), and augmentation index-75 (P < 0.0001) measured in the first trimester of pregnancy were significantly higher in the women who later developed hypertensive disorders of pregnancy than in those who remained normotensive. The aSp (sensitivity 72.6%; specificity 59.6%) was found to be the best predictor for the later development of hypertension. In normotensive, low-risk pregnant women, PWA may be useful for the early detection of risk for the development of hypertensive disorders of pregnancy.


Ruthenium catalysts for water oxidation involving tetradentate polypyridine-type ligands.
A series of Ru(II) complexes that behave as water oxidation catalysts were prepared involving a tetradentate equatorial ligand and two 4-substituted pyridines as the axial ligands. Two of these complexes were derived from 2,9-di-(pyrid-2'-yl)-1,10-phenanthroline (dpp) and examine the effect of incorporating electron-donating amino and bulky t-butyl groups on catalytic activity. A third complex replaced the two distal pyridines with N-methylimidazoles that are more electron-donating than the pyridines of dpp and potentially stabilize higher oxidation states of the metal. The tetradentate ligand 2-(pyrid-2'-yl)-6-(1'',10''-phenanthrol-2''-yl)pyridine (bpy-phen), possessing a bonding cavity similar to dpp, was also prepared. The Ru(II) complex of this ligand does not have two rotatable pyridines in the equatorial plane and thus shows different flexibility from the [Ru(dpp)] complexes. All the complexes showed activity towards water oxidation. Investigation of their catalytic behavior and electrochemical properties suggests that they may follow the same catalytic pathway as the prototype [Ru(dpp)pic2](2+) involving a seven-coordinated [Ru(IV)(O)] intermediate. The influence of coordination geometry on catalytic performance is analyzed and discussed.


The accuracy of SpaceLabs 90207 in blood pressure monitoring in patients with atrial fibrillation.
Irregular heart rhythm in the course of atrial fibrillation (AFib) results in lower blood pressure (BP) measurements reproducibility which is further limited by various BP-monitors used. Therefore the aim of our study was to estimate accuracy of oscillometric BP measurement (SpaceLabs 90207) with reference to mercury manometer-based readings. Study was performed in 47 hemodynamically stable patients aged 63 ± 12 yo with paroxysmal or persistent AFib, at baseline. Patients were reassessed within one week after effective cardioversion (SR; n = 29). BP was measured using Y-tube connection allowing for simultaneous measurements on the same arm with SpaceLabs 90207 and referral method. Mean values were tested with paired t-tests. Additionally, concordance correlation coefficient (ρc) and Bland-Altman plots were assessed. Results were confronted with AAMI, and ESH-IP criteria. Both during arrhythmia and sinus rhythm diastolic BP differed significantly (Δ = 4.6 ± 6.0 mm Hg, p < .001 and 2.1 ± 4.0 mm Hg, p < .001; for AFib, and SR, respectively), which was not the case for systolic BP. The ρc during arrhythmia equaled 0.89, and 0.75 for systolic and diastolic BP, respectively, which further improved while SR (0.96 and 0.89, respectively). Results confronted against AAMI and ESH-IP showed that all criteria were met except for one (60% vs. required 65% of paired differences of less than 5 mm Hg) during AFib. The direct comparisons of BP readings allowed to conclude that diastolic blood pressure tended to be slightly overestimated when assessed with SpaceLabs 90207 in patients with both, AFib and SR, which was not a case for systolic BP. When the results were confronted with available validation protocols requirements, all referral criteria were met except for one. Taken together, our results suggest acceptable BP readings dispersion of SpaceLabs 90207 in BP monitoring of patients with both AFib and SR.


[Exhaled nitric oxide in patients with obstructive sleep apnea syndrome].
Exhaled nitric oxide has been extensively investigated as a non-invasive marker of airway inflammation. Some authors have suggested that morning FE(NO) in obstructive sleep apnea syndrome (OSAS) patients is elevated due to inflammation of upper airways, while others have not found any differences between patients and healthy subjects. The purpose of this study was to analyze concentration of exhaled nitric oxide (FE(NO)) in OSAS patients. 119 (99 M, 20 F) consecutive patients of sleep laboratory participated in this study. Standard overnight sleep studies with polysomnography or portable screening device were carried out in the whole group: OSAS was diagnosed in 66 patients and 53 no-OSAS served as controls. FE(NO) was measured on-line with a flow rate kept at 0.045 - 0.055 l/s, according to the recommendations of ATS using a chemiluminescence analyzer twice: before the sleep study (8-10 p.m.) and after termination of data collection (6 - 8 a.m.). There were no differences in age between patients and controls. Respiratory disturbance index (RDI) was 40.3+/-24.9 in patients and 3.7+/-2.8 in controls (p<0.001). In OSAS patients both evening and morning FE(NO) was significantly higher compared to controls (23.1+/-14.8 ppb vs. 16.8+/-9.8 ppb and 22.4+/-13.2 ppb vs. 15.3+/-8.1 ppb respectively, p<0.05). Weak but statistically significant correlations for the whole group between morning FE(NO) and mean and minimum arterial oxygen saturation (SaO2) during sleep and number of study minutes with SaO2<90% were observed. Lower evening FE(NO) in OSAS patients with coexisting arterial hypertension when compared to normotensive OSAS patients was also noticed (19.1+/-10.8 ppb vs. 27.1+/-19.1 ppb; p<0.05). The increase in FE(NO) in OSAS patents may be caused by repetitive apneas and hypoxemia during sleep.


[Scientific bases and technological principles of the production of gerodietetic canned milk].
It is well known that aging is the natural growing multisection biological process inevitably leading to limitation of body adaptive capabilities. The body ageing is the result of self-regulation mechanism limitation, reduction of their potential capabilities at molecular-genetic, energetic, cellular and general-regulatory levels. It should be noted that due to lack of the unified theory of aging the importance of nutrition factor has been acknowladged particularly initiation and intensity of the process, and the role of antioxidants is discussed much in detail. As the result of long term investigations at model and natural objects the technologies of powder and condensed sterilized gerodietetic milk based preserved foods have been developed. The multicomponent receipts modules balanced by fatty-acid and amino-acid composition as well as enriched with lycopene have been theoretically substantiated and realized. The new gerodietetic products are characterized by the following coefficients of RL3/RL6 not less than for the products: powdered - 0.871/0.615 and condensed sterilized - 0.883/0.648. The following amino-acid balance of Rp/σ protein for the products: powdered - 0.46/15.00, condensed -0.44/15.76 has been obtained. The obtained velues of the balanced criteria of the protein-lipid composition of the product are higher comparing to similar values for milk fat and protein. Two lycopene dosages in the products are provided: prophylactic - 5 mg and antioxidant - 1.5 mg in 400 ml of the reconstituted milk. On the basis of the carried out studies two technologies of the manufacture of condensed milk gerodietetic products adapted to actual conditions of concentrated milk factories have been developed.


MR Venous Flow in Sigmoid Sinus Diverticulum.
Case reports demonstrate that coiling of a sigmoid sinus diverticulum can treat pulsatile tinnitus. We hypothesized that MR imaging 4D flow and computational fluid dynamics would reveal distinct blood flow patterns in the venous outflow tract in these patients. Patients with pulsatile tinnitus of suspected venous etiology underwent MR imaging at 3T, using venous phase contrast-enhanced MR angiography, 4D flow, and 2D phase contrast. The contrast-enhanced MRA contours were evaluated to determine the presence and extent of a sigmoid sinus diverticulum. Computational fluid dynamics analysis was performed using the 4D flow inlet flow and the luminal contours from contrast-enhanced MRA as boundary conditions. In addition, computational fluid dynamics was performed for the expected post treatment conditions by smoothing the venous geometry to exclude the sigmoid sinus diverticulum from the anatomic boundary conditions. Streamlines were generated from the 4D flow and computational fluid dynamics velocity maps, and flow patterns were examined for the presence of rotational components. Twenty-five patients with pulsatile tinnitus of suspected venous etiology and 10 control subjects were enrolled. Five (20%) of the symptomatic subjects had sigmoid sinus diverticula, all associated with an upstream stenosis. In each of these patients, but none of the controls, a stenosis-related flow jet was directed toward the opening of the sigmoid sinus diverticulum with rotational flow patterns in the sigmoid sinus diverticulum and parent sigmoid sinus on both 4D flow and computational fluid dynamics. Consistent patterns of blood flow can be visualized in a sigmoid sinus diverticulum and the parent sinus using 4D flow and computational fluid dynamics. Strong components of rotational blood flow were seen in subjects with sigmoid sinus diverticula that were absent in controls.


Fluorometric Biosniffer Camera "Sniff-Cam" for Direct Imaging of Gaseous Ethanol in Breath and Transdermal Vapor.
Various volatile organic compounds can be found in human transpiration, breath and body odor. In this paper, a novel two-dimensional fluorometric imaging system, known as a "sniffer-cam" for ethanol vapor released from human breath and palm skin was constructed and validated. This imaging system measures ethanol vapor concentrations as intensities of fluorescence through an enzymatic reaction induced by alcohol dehydrogenase (ADH). The imaging system consisted of multiple ultraviolet light emitting diode (UV-LED) excitation sheet, an ADH enzyme immobilized mesh substrate and a high-sensitive CCD camera. This imaging system uses ADH for recognition of ethanol vapor. It measures ethanol vapor by measuring fluorescence of nicotinamide adenine dinucleotide (NADH), which is produced by an enzymatic reaction on the mesh. This NADH fluorometric imaging system achieved the two-dimensional real-time imaging of ethanol vapor distribution (0.5-200 ppm). The system showed rapid and accurate responses and a visible measurement, which could lead to an analysis of metabolism function at real time in the near future.


Caring behaviours directly and indirectly affect nursing students' critical thinking.
The purpose of this study was to determine the effect of caring behaviours on critical thinking and to examine whether self-reflection mediates the effect of caring on critical thinking. We also tested whether caring behaviours moderated the relationship between self-reflection and critical thinking. For this descriptive, correlational, cross-sectional study, we recruited 293 fifth-year nursing students from a junior college in southern Taiwan. Data were collected in 2014 on critical thinking, caring behaviours and self-reflection with insight using the Taiwan Critical Thinking Disposition Inventory, a Chinese version of the Caring Assessment Report Evaluation Q-sort, and a Chinese version of the Self-Reflection and Insight Scale, respectively. Relationships among variables were analysed by structural equation modelling, with the partial least squares method and Sobel test. The results showed that caring behaviours significantly positively affected critical thinking (β = 0.56, t = 12.37, p < 0.001) and self-reflection with insight (β = 0.54, t = 11.99, p < 0.001). Self-reflection and insight significantly positively affected critical thinking (β = 0.34, t = 6.48, p < 0.001). Further, self-reflection and insight mediated the relationship between caring behaviours and critical thinking. Caring behaviours did not, however, moderate the relationship between self-reflection (β = 0.001, t = 0.021, p > 0.05) and critical thinking. Caring behaviours directly affect self-reflection with insight and critical thinking. In addition, caring behaviours also indirectly affect critical thinking through self-reflection and insight.


Resting-state Electroencephalography Microstates Correlate with Pain Intensity in Patients with Complex Regional Pain Syndrome.
Objective: Severe pain and other symptoms in complex regional pain syndrome (CRPS), such as allodynia and hyperalgesia, are associated with abnormal resting-state brain network activity. No studies to date have examined resting-state brain networks in CRPS patients using electroencephalography (EEG), which can clarify the temporal dynamics of brain networks. Methods: We conducted microstate analysis using resting-state EEG signals to prospectively reveal direct correlations with pain intensity in CRPS patients (n = 17). Five microstate topographies were fitted back to individual CRPS patients' EEG data, and temporal microstate measures were subsequently calculated. Results: Our results revealed five distinct microstates, termed microstates A to E, from resting EEG data in patients with CRPS. Microstates C, D and E were significantly correlated with pain intensity before pain treatment. Particularly, microstates D and E were significantly improved together with pain alleviation after pain treatment. As microstates D and E in the present study have previously been related to attentional networks and the default mode network, improvement in these networks might be related to pain relief in CRPS patients. Conclusions: The functional alterations of these brain networks affected the pain intensity of CRPS patients. Therefore, EEG microstate analyses may be used to identify surrogate markers for pain intensity.


Molecular approaches to the genetic analysis of specific reading disability.
Specific reading disability is a complex phenotype that is under both genetic and environmental influences. There is evidence for at least one major gene, which may be detectable by parametric linkage analysis, but detection of other quantitative trait loci may require nonparametric methods. Phenotype definition may also be critical in identifying genes that affect different components of the reading process. Current research from two separate laboratories supports the localization of one gene influencing reading disability to the histocompatibility region of chromosome 6p and suggests that another gene may be located on chromosome 15. Actual identification of these and similar genes is complicated by reduced penetrance and phenocopies in families, so that delineation of the critical region using crossover analysis is problematic. This difficulty can result in the identification of many candidate genes that need to be evaluated through combinations of association analysis, functional analysis, and mutation assays.


[Cerebral blood flow and depression].
Regional cerebral blood flow is an index of cerebral metabolism. We have studied with the Xenon 113 inhalation method, regional cerebral blood flow (CBF) in patients with various types of depression and in remission. A left frontal hypervascularisation and a right posterior hypovascularisation have been found in primary major depression, but not in minor depression and bipolar depression in remission. These results confirm and complete results from other authors who have studied the physiopathology of depression with other technics.


Evaluation of Four Biomarkers in Patients Chronically Infected with Trypanosoma cruzi and Their Relationship with Disease Progression.
This study evaluated four biomarkers of inflammation or fibrosis as progression indicators for heart disease in patients with Chagas disease. We compared values of these markers at the time of the first sample collection of blood (first time point) and at the time of the last collection of blood (second time point) for 103 individuals positive for Trypanosoma cruzi antibodies. They were split into two clinical groups: 52 individuals with the indeterminate form of the disease at the first time point and 51 controls that already had either cardiac involvement (N = 25) or megaviscera (megaesophagus and/or megacolon; N = 26) at that time. All individuals had an electrocardiogram performed both at the first and second time point (mean time between time points: 11 years). All samples were blind tested for galectin-3, brain natriuretic peptide (NT-proBNP), lysyl oxidase-like protein 2 (LOXL2), and troponin. Differences in concentrations between samples were analyzed using the months between samples as the covariate. This analysis showed that values for all markers, except troponin biomarkers had a significative increase at the second time point for the 91 patients without progression. A similar result was obtained for NT-proBNP and LOXL2 with sera from 12 patients that progressed with cardiac disease. The single marker that showed a significative difference between groups (P = 0.01) was galectin-3. We concluded that galectin-3 was the only marker with a prognostic value in relation to the progression or worsening of heart disease in patients with Chagas disease.


A Theoretical Study on the Mechanism of the Oxidative Deborylation/C-C Coupling Reaction of Borepin Derivatives.
One-electron oxidation of borepin derivatives that consists of a boron-containing seven-membered ring has been reported to cause deborylation/C-C coupling, yielding aromatic compounds. The reaction can be achieved not only by transition metal compounds but also by oxidants without transition metal such as O2 and other organic compounds. Despite numerous experimental attempts, the mechanism of this peculiar reaction as well as the fate of the BCl part eliminated from borepin remain unclear to date. Based on theoretical approaches using the artificial force induced reaction method, here we address the mechanism of the unusual boron-mediated C-C coupling. For this purpose, two borepin derivatives (1 and 35), bearing ethyl and phenyl groups, respectively, were used as reactants, and FeCl3/MeNO2 and O2 were chosen as oxidants. The calculations revealed reaction pathways that provided an overall picture of the mechanism of the target reaction, which features four key steps, namely, (i) quaternization of the boron atom by the coordination of oxidant, (ii) intersystem crossing, (iii) skeletal rearrangement to form a six-membered ring, and (iv) elimination of a boron moiety. The intrinsic nature of boron, i.e., a strong tendency to accept a coordination ligand even under oxidative conditions, is responsible for the oxidative deborylation/C-C coupling of borepin.


Single-Surgery Co-Implantation of Autologous Primary Articular Chondrocytes with Bone Marrow Cells in the Treatment of Articular Cartilage Lesions: Observations from the Operating Room on Tissue Input and Cell Output.
Single-surgery variants of autologous chondrocyte implantation to repair cartilage are emerging, but practical data on such procedures are scarce. We set out to describe a 1-stage autologous chondrocyte co-implantation procedure and include quantitative characteristics of the biopsy tissues collected and of the cells obtained from those tissues in the operating room. Data concerning patient age, articular cartilage lesion size and location, as well as measurements of cartilage biopsy mass, bone marrow aspirate volume, and the cell yields harvested from those biopsies were intraoperatively collected for 141 patients. The mean patient age was 35.7 ± 9.8 years, and the mean total lesion size was 4.0 ± 3.1 cm2. Cartilage biopsy mass ranged from 0.19 to 2.0 gram and provided a mean yield of 1.23 × 106 chondrocytes/gram. Bone marrow aspirate volume ranged from 7.2 to 62 milliliters and provided a mean yield of 7.18 × 106 mononuclear cells/mL. The cell yields did not correlate with patient age, which ranged from 12 to 57 years. The mean primary chondrocyte supply was 272 thousand per cm2 of lesion, ranging from 10.4 thousand to 1.07 million per cm2. The total cell supply was kept at 9 million cells per cm2 of lesion by adding mononuclear cells to the chondrocytes. The mean tissue processing time was 100 ± 19 minutes, which was frequently used to perform concurrent interventions. Single-surgery co-implantation of clinically relevant numbers of autologous primary articular chondrocytes and bone marrow cells is feasible for a wide range of ages and lesion sizes.


Recent Advances in Aggregation-Induced Emission Materials and Their Biomedical and Healthcare Applications.
The emergence of the concept of aggregation-induced emission (AIE) has opened new opportunities in many research areas, such as biopsy analysis, biological processes monitoring, and elucidation of key physiological and pathological behaviors. As a new class of luminescent materials, AIE luminogens (AIEgens) possess many prominent advantages such as tunable molecular structures, high molar absorptivity, high brightness, large Stokes shift, excellent photostability, and good biocompatibility. The past two decades have witnessed a dramatic growth of research interest in AIE, and many AIE-based bioprobes with excellent performance have been widely explored in biomedical fields. This review summarizes some of the latest advancements of AIE molecular probes and AIE nanoparticles (NPs) with regards to biomedical and healthcare applications. According to the research areas, the review is divided into five sections, which are imaging and identification of cells and bacteria, photodynamic therapy, multimodal theranostics, deep tissue imaging, and fluorescence-guided surgery. The challenges and future opportunities of AIE materials in the advanced biomedical fields are briefly discussed. In perspective, the AIE-based bioprobes play vital roles in the exploration of advanced bioapplications for the ultimate goal of addressing more healthcare issues by integrating various cutting-edge modalities and techniques.


Navigating the complex landscape of benzodiazepine- and Z-drug diversity: insights from comprehensive FDA adverse event reporting system analysis and beyond.
Medications which target benzodiazepine (BZD) binding sites of GABAA receptors (GABAARs) have been in widespread use since the nineteen-sixties. They carry labels as anxiolytics, hypnotics or antiepileptics. All benzodiazepines and several nonbenzodiazepine Z-drugs share high affinity binding sites on certain subtypes of GABAA receptors, from which they can be displaced by the clinically used antagonist flumazenil. Additional binding sites exist and overlap in part with sites used by some general anaesthetics and barbiturates. Despite substantial preclinical efforts, it remains unclear which receptor subtypes and ligand features mediate individual drug effects. There is a paucity of literature comparing clinically observed adverse effect liabilities across substances in methodologically coherent ways. In order to examine heterogeneity in clinical outcome, we screened the publicly available U.S. FDA adverse event reporting system (FAERS) database for reports of individual compounds and analyzed them for each sex individually with the use of disproportionality analysis. The complementary use of physico-chemical descriptors provides a molecular basis for the analysis of clinical observations of wanted and unwanted drug effects. We found a multifaceted FAERS picture, and suggest that more thorough clinical and pharmacoepidemiologic investigations of the heterogenous side effect profiles for benzodiazepines and Z-drugs are needed. This may lead to more differentiated safety profiles and prescription practice for particular compounds, which in turn could potentially ease side effect burden in everyday clinical practice considerably. From both preclinical literature and pharmacovigilance data, there is converging evidence that this very large class of psychoactive molecules displays a broad range of distinctive unwanted effect profiles - too broad to be explained by the four canonical, so-called "diazepam-sensitive high-affinity interaction sites". The substance-specific signatures of compound effects may partly be mediated by phenomena such as occupancy of additional binding sites, and/or synergistic interactions with endogenous substances like steroids and endocannabinoids. These in turn drive the wanted and unwanted effects and sex differences of individual compounds.


The effects of the selective 5-HT(2C) receptor antagonist SB 242084 on learned helplessness in male Fischer 344 rats.
Rats exposed to an uncontrollable stressor demonstrate a constellation of behaviors such as exaggerated freezing and deficits in shuttle box escape learning. These behaviors in rats have been called learned helplessness and have been argued to model human stress-related mood disorders. Learned helplessness is thought to be caused by hyperactivation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) and a subsequent exaggerated release of 5-HT in DRN projection sites. Blocking 5-HT(2C) receptors in the face of an increase in serotonin can alleviate anxiety behaviors in some animal models. However, specific 5-HT receptor subtypes involved in learned helplessness remain unknown. The current experiments tested the hypothesis that 5-HT(2C) receptor activation is necessary and sufficient for the expression of learned helplessness. The selective 5-HT(2C) receptor antagonist SB 242084 (1.0 mg/kg) administered i.p. to adult male Fischer 344 rats prior to shuttle box behavioral testing, but not before stress, blocked stress-induced deficits in escape learning but had no effect on the exaggerated shock-elicited freezing. The selective 5-HT(2C) receptor agonist CP-809101 was sufficient to produce learned helplessness-like behaviors in the absence of prior stress and these effects were blocked by pretreatment with SB 242084. Results implicate the 5-HT(2C) receptor subtype in mediating the shuttle box escape deficits produced by exposure to uncontrollable stress and suggest that different postsynaptic 5-HT receptor subtypes underlie the different learned helplessness behaviors.


Natural killer cells and the immune response in solid organ transplantation.
Natural killer (NK) cells have been characterized classically for their cytotoxicity against pathogen infected or stressed cells as well as for their role in monitoring the expression of self MHC I. However, the participation of NK cells in solid organ transplantation (SOT) is poorly defined due to conflicting clinical and animal model data. Preclinical models have shown that NK cells exacerbate T-cell allogeneic responses during rejection, but can also promote tolerance induction under immunosuppressive conditions. Further, while protocols such as costimulatory blockade effectively induce tolerance by blocking T-cell activation and promoting Treg generation, how such regimens regulate other innate and adaptive immune cells, including NK cells, is incomplete. This review examines NK cells and the regulation of their effector functions in SOT.


Sleep complaints and metabolic syndrome in an elderly population: the Three-City Study.
To assess whether sleep complaints (rather than clinically defined sleep disturbances) were associated with the metabolic syndrome (MetS) and each of its components in an elderly population. Cross-sectional analyses of data from the French Three City Study, a large multicenter cohort of elderly community-dwellers. 6,354 participants (56.4% women, median age 73; range: 65-97 years). Frequency of insomnia complaints (difficulty in initiating sleep, difficulty in maintaining sleep [DMS], and early morning awakening) and excessive daytime sleepiness (EDS) were self-reported. MetS was assessed using National Cholesterol Education program Adult Treatment Panel III criteria. A total of 977 participants had MetS. After adjustment for a large range of potential confounders, we report an association between the number of insomnia complaints and MetS. Among insomnia complaints only DMS was consistently associated with MetS (OR: 1.23, 95% CI: 1.06 to 1.43). Our results showed that EDS independently increased the risk of MetS (OR: 1.46, 95% CI: 1.18 to 1.81 for "frequently"; OR: 1.99, 95% CI: 1.49 to 1.67 for "often"). The EDS-MetS association was independent of past-history of cardiovascular disease, insomnia complaints, and obesity and loud snoring. We report significant independent associations between frequent sleep complaints (EDS and to a lesser extent DMS) and MetS in the elderly with potential implications in terms of management and cardiovascular prevention in general geriatric practice. Prospective studies are required to clarify the direction of the association between sleep complaints and MetS.


Genome-wide association mapping for phenotypic plasticity in rice.
Phenotypic plasticity of plants in response to environmental changes is important for adapting to changing climate. Less attention has been paid to exploring the advantages of phenotypic plasticity in resource-rich environments to enhance the productivity of agricultural crops. Here, we examined genetic variation for phenotypic plasticity in indica rice (Oryza sativa L.) across two diverse panels: (1) a Phenomics of Rice Adaptation and Yield (PRAY) population comprising 301 accessions; and (2) a Multi-parent Advanced Generation Inter-Cross (MAGIC) indica population comprising 151 accessions. Altered planting density was used as a proxy for elevated atmospheric CO2 response. Low planting density significantly increased panicle weight per plant compared with normal density, and the magnitude of the increase ranged from 1.10 to 2.78 times among accessions for the PRAY population and from 1.05 to 2.45 times for the MAGIC population. Genome-wide-association studies validate three Environmental Responsiveness (ER) candidate alleles (qER1-3) that were associated with relative response of panicle weight to low density. Two of these alleles were tested in 13 genotypes to clarify their biomass responses during vegetative growth under elevated CO2 in Japan. Our study provides evidence for polymorphisms that control rice phenotypic plasticity in environments that are rich in resources such as light and CO2 .


Crystallization-Induced Emission Enhancement of a Deep-Blue Luminescence Material with Tunable Mechano- and Thermochromism.
Organic luminescent materials with the ability to reversibly switch the luminescence when subjected to external stimuli have attracted considerable interest in recent years. However, the examples of luminescent materials that exhibit multiresponsive properties are rarely reported. In this work, a new stimuli-responsive dye P1 is designed and synthesized with two identical chromophores of naphthalimide, one at each side of an amidoamine-based spacer. This amide-rich molecule offers many possibilities for forming intra- and intermolecular hydrogen bond interactions. Particularly, P1 has an intrinsic property of cocrystallizing with methanol. Compared with the pristine P1 sample, the as-prepared two-component cocrystalline material displays an exceptive deep-blue emission, which is extremely rare among naphthalimide-based molecules in the solid state. Furthermore, the target material exhibits an obvious mechanochromic fluorescent behavior and a large spectral shift under force stimuli. On the other hand, the cocrystalline material shows an unusual "turn off" thermochromic luminescence accompanied by solvent evaporation. Moreover, using external stimuli to reversibly manipulate fluorescent quantum yields is rarely reported to date. The results demonstrate the feasibility of a new design strategy for solid-state luminescence switching materials: the incorporation of solvents into organic compounds by cocrystallization to obtain a crystalline state luminescence system.


Biologic therapy of inflammatory bowel disease.
Advancing knowledge regarding the biology of chronic inflammation has led to the development of specific biologic therapies that mechanistically target individual inflammatory pathways. Many biologic therapies are being evaluated for the treatment of the chronic inflammatory bowel diseases, Crohn's disease and ulcerative colitis. Biologic compounds proven to be effective for Crohn's disease include monoclonal antibodies to tumor necrosis factor (infliximab and CDP571) and to the leukocyte adhesion molecule alpha4 integrin (natalizumab). Other biologic compounds for which there is insufficient evidence to judge efficacy for inflammatory bowel disease include: p55 tumor necrosis factor binding protein (onercept); interferon alpha; interferon beta-1a; anti-interferon gamma antibody; anti-interleukin 12 antibody; p65 anti-sense oligonucleotide (blocks NF-kappaB); granulocyte colony stimulating factor, and granulocyte macrophage colony stimulating factor; anti-interleukin 2 receptor antibody; epidermal growth factor; keratinocyte growth factor 2 (repifermin); human growth hormone; anti-CD4 antibody; and anti-alpha4beta7 antibody. Biologic therapies that have been proven ineffective for inflammatory bowel disease include: interleukin 10; interleukin 11; anti-sense intercellular adhesion molecule-1; and the tumor necrosis factor receptor fusion protein etanercept. Based on the early successes of infliximab, CDP571 and natalizumab, it seems certain that biologic therapy will play an important role in the future treatment of inflammatory bowel disease.


Detection of human papillomavirus distinguishes second primary tumors from lung metastases in patients with squamous cell carcinoma of the cervix.
In patients with squamous cell carcinoma of the cervix (SCCC), a squamous cell carcinoma (SqCC) in the lung represents either a second primary tumor or metastasis. This distinction between second primary tumors and lung metastases in patients with SCCC significantly influences patient prognosis and therapy. Here, we aimed to differentiate second primary tumors from lung metastases in patients with SCCC by exploring the HPV status in SqCCs involving the lung within a large cohort. P16 expression was assessed using immunohistochemistry on tissue microarrays including a total of 415 primary lung SqCCs and 21 lung SqCCs with prior SCCC. Following this, we performed HPV DNA typing and the sensitive RNAscope in situ method to screen all the cases for HPV E6/E7 expression, which is a more reliable indicator of transcriptively active HPV in tumor cells. The p16 positive expression rate was 13.7% (57/415) in primary lung SqCCs, but HPV DNA was not detected in any of the 57 primary lung SqCC cases that positively expressed p16. In contrast, HPV DNA was detected in all cases (21/21) with prior SCCC. Consistently, all 21 lung SqCCs with prior SCCC (21/21) showed extensive HPV16 E6/E7 expression. In striking contrast, none of the primary lung SqCCs (0/415) had a detectable RNAscope signal. HPV does not seem to play a role in the development of primary lung SqCCs. HPV detection may be helpful in distinguishing second primary tumors from lung metastases in patients with SCCC.


A possible neural cascade involving the photoneuroendocrine system (PNES) responsible for regulating gonadal development in an avian species, Gallus gallus.
Neurons located in the lateral septal organ (LSO) and medial basal hypothalamus (MBH) have been proposed to be encephalic photoreceptors (EPRs), which sense photoperiodic time and initiate avian gonadal development. Controversy continues regarding the location of EPRs serving the PNES and their signal transduction pathway. Using quantitative real-time RT-PCR we determined activation of key genes following prolonged light periods and sulfamethethazine (compound known to advance light-induced testes development) in 21-day old chicks. Earliest activation occurred in genes of vasoactive intestinal polypeptide (VIP) and type 6 phosphodiesterase beta subunit (PDE-6 beta) in the LSO at 4 and 6h, respectively, after onset of light and sulfamethazine intake. In contrast, no change was detected in the MBH during the first 8h of that treatment. Thereafter, significant increases in gonadotropin releasing hormone (GnRH-1) and VIP receptor (VIPR) mRNA transcripts were detected in the bed nucleus of the pallial commissure (NCPa). Hours later, activation of all four genes (VIP, PDE-6 beta, GnRH-1, VIPR) were induced solely by photostimulation. Deiodinase 2 and tyrosine hydroxylase in the MBH did not show increased gene expression until 12h of photostimulation. Prolactin mRNA transcripts showed significant increases at 4h due to SMZ intake and at 24, 36 and 48 h due to long-day photoperiodic effects. Data suggest that VIP neurons in the LSO may serve as EPRs and utilize PDE, present in the phototransduction cascade of known photoreceptors. Additionally, VIP released from the LSO may modulate GnRH-1 neurons in the NCPa via VIP receptors by increasing GnRH-1 gene expression.


Barut-Girardello coherent states for anisotropic 2D-Dirac materials.
We construct the Barut-Girardello coherent states for charge carriers in anisotropic 2D-Dirac materials immersed in a constant homogeneous magnetic field which is orthogonal to the sample surface. For that purpose, we solve the anisotropic Dirac equation and identify the appropriate arising and lowering operators. Working in a Landau-like gauge, we explicitly construct nonlinear coherent states as eigenstates of a generalized annihilation operator with complex eigenvalues which depends on an arbitrary function f of the number operator. In order to describe the anisotropy effects on these states, we obtain the Heisenberg uncertainty relation, the probability density, mean energy value and occupation number distribution for three different functions f . For the case in which the anisotropy is caused by uniaxial strain, we obtain that when the stress is applied along the x-axis of the material surface, the probability density for the nonlinear coherent states is smaller compared to when the material is stressed along the orthogonal axis.


Crystal structures and molecular dynamics simulations of thermophilic malate dehydrogenase reveal critical loop motion for co-substrate binding.
Malate dehydrogenase (MDH) catalyzes the conversion of oxaloacetate and malate by using the NAD/NADH coenzyme system. The system is used as a conjugate for enzyme immunoassays of a wide variety of compounds, such as illegal drugs, drugs used in therapeutic applications and hormones. We elucidated the biochemical and structural features of MDH from Thermus thermophilus (TtMDH) for use in various biotechnological applications. The biochemical characterization of recombinant TtMDH revealed greatly increased activity above 60 °C and specific activity of about 2,600 U/mg with optimal temperature of 90 °C. Analysis of crystal structures of apo and NAD-bound forms of TtMDH revealed a slight movement of the binding loop and few structural elements around the co-substrate binding packet in the presence of NAD. The overall structures did not change much and retained all related positions, which agrees with the CD analyses. Further molecular dynamics (MD) simulation at higher temperatures were used to reconstruct structures from the crystal structure of TtMDH. Interestingly, at the simulated structure of 353 K, a large change occurred around the active site such that with increasing temperature, a mobile loop was closed to co-substrate binding region. From biochemical characterization, structural comparison and MD simulations, the thermal-induced conformational change of the co-substrate binding loop of TtMDH may contribute to the essential movement of the enzyme for admitting NAD and may benefit the enzyme's activity.


Are diagnostic lumbar facet injections influenced by pain of muscular origin?
Nonradicular low back pain can be a difficult entity to accurately diagnose and treat. Facet joints, muscle, ligaments, and fascia have all been reported to be etiologies of acute and chronic low back pain. However, the facet joint as a source of low back pain is controversial. The diagnosis of facet joint pain is made by diagnostic facet joint or median nerve branch injections with a local anesthetic. The purpose of this study was to determine if the results of diagnostic facet joint injections are influenced by the technique used to perform these injections. Seventy-five male patients aged 45 years or younger and 18 years or older who were injured while performing heavy work with nonradicular low back pain were included in this study. Diagnostic injection therapy was performed following Institutional Review Board approval and the patient's informed consent. Patients were assigned to one of five groups to receive diagnostic injections in a double-blinded fashion as follows: Group I: facet joint injection with continuous lidocaine administration from the skin to the facet joint as the needle was advanced; Group II: facet joint injection with saline administration from the skin to the facet joint as the needle was advanced; Group III: median nerve branch injection with a lidocaine advancing needle technique; Group IV: median nerve branch injection with saline advancing needle technique; and Group V: injection of the paraspinous muscles with local anesthetic and steroid following noted areas of pain diagnosed with saline injection and radiopaque contrast. After one week, the patients in Groups I to IV who had no pain relief with facet joint or median nerve block injections subsequently received paraspinous muscle injections, while the patients in Group V who had no long-term relief with muscle injections were given facet joint injections. The appropriate parametric and nonparametric tests were performed with statistical significance defined as P < or = 0.05. There were no differences among the groups demographically. The incidence of pain relief was significantly higher in subjects who had a continuous injection of local anesthetic into their musculature than in those individuals who received continuous saline followed by an injection of local anesthetic into their facet joint or median nerve branch. The results of this study demonstrated that local anesthetic injections are useful for the diagnosis of nonradicular low back pain but may yield false positive results with respect to lumbar facet pain depending upon the technique utilized.


Did he drown or was he murdered?
An unemployed, 60-year-old Singaporean gentleman died during a brief overseas trip to another South-East Asian country. He had, presumably, drowned in the bathtub of his hotel room, which he shared with his then 44-year-old companion, who was supposedly his nephew. The relevant public health and medico-legal authorities of the host country conducted an external examination of the body at the scene, whereupon they agreed with the police that his death was probably due to accidental drowning following an episode of syncope. It would appear that this verdict was based almost entirely on circumstantial and hearsay evidence. No autopsy was performed. In its place, considerable reliance was placed on the observation that abdominal compression resulted in the outflow of a small amount of water from the mouth, as being proof of drowning. A few days later, the body was cremated in the host country and the remains (ashes) were subsequently repatriated to Singapore. It later transpired that, shortly before they embarked on the ill-fated trip, the deceased's 'nephew' had purchased, on the former's behalf, travel insurance policies (covering accidental injury and death) amounting to a total of S$800,000 from five different insurance companies, as well as a separate life policy for a further S$100,000, most of which had been issued within the fortnight prior to their departure. Interestingly, the beneficiary (later the plaintiff in the ensuing civil trial some three years later) of all of these policies, was the ex-wife of the deceased's 'nephew', with whom he had, in fact, continued to live although they were officially divorced several years ago. Whilst the claim against the life policy had been settled, the first five insurers declined to issue payment on grounds of suspicion that the deceased had been the victim of a homicide, planned or executed by the 'nephew', wherein the beneficiary was a conspirator of sorts. The author was approached by defence counsel (representing the various insurers), for assistance in this matter. It was felt that a proper forensic review was seriously hampered by the lack of a full autopsy which would have been indispensable in ascertaining the actual cause of death and in eliminating other possibilities, apart from drowning, such as death from natural causes, other forms of injury, poisoning, or homicide. It was also emphasized that the mere presence of ingested water is not diagnostic of drowning. Eventually, after a protracted but unsuccessful attempt at mediation (in the course of which, the plaintiff rejected the offer of a reduced, although apparently sizable quantum), the matter came before the High Court, which found in favour of the defendants. It appeared that the judge was more than convinced that the deceased was indeed the victim of a homicide of which the plaintiff was a conspirator and her ex-husband, the perpetrator, as even a cursory perusal of the written judgement would indicate. Accordingly, the court ruled that the plaintiff (in her capacity as both the beneficiary of the insurance policies and executor of the estate) and her ex-husband had, effectively, deprived the insurers of their contractual right (as stipulated in the insurance policies) to have an autopsy conducted on the body of the deceased and they were, therefore, entitled to deny liability. This case illustrates the difficulties inherent in conducting an independent review of a putative instance of drowning, where convincing and reliable forensic evidence and documentation are largely wanting; this being compounded by its occurrence in a foreign jurisdiction whose medico-legal practices differ substantially from that to which one is accustomed. It may even be said that the corpus delecti was destroyed, in this instance, by cremation. It is also unusual in that a de-facto finding of murder was made in a civil court (whose standard of proof is that of a balance of probabilities) and that this had, subsequently, spurred the police to undertake a criminal investigation for conspiracy to murder. In the event, the civil appeal was dismissed by the Court of Appeal, but no charge was laid against any of the suspects for want of sufficient forensic or investigative evidence of a criminal offence having been committed.


Regulated formation and selection of neuronal processes underlie directional guidance of neuronal migration.
Axon guidance and neuronal migration are critical features of neural development, and it is believed that extracellular gradients of secreted guidance cues play important roles in pathfinding. It has been well documented that the growth cones of extending axons respond to such extracellular gradients by growing toward or away from the source of the secreted cue via asymmetrical extension of a single growth cone. However, it is unclear whether migrating neurons change direction in response to guidance molecules using the same mode of turning as extending axons. In this study, we demonstrate that migrating neurons turn away from the chemo-repellent Slit through repeated rounds of process extension and retraction and do not turn through the reorientation of a single growth cone. We further show that Slit increases the rate of somal process formation and that these processes form preferentially on the side of the cell body furthest away from the Slit source. In addition, Slit causes cell turning through asymmetric process selection. Finally, we show that multiple types of migrating neurons employ this mode of cell turning in response to a variety of guidance cues. These results show that migrating neurons employ a unique type of turning when faced with secreted guidance cues that is distinct from the type employed by axons.


Comparison of phenotypic markers and neural differentiation potential of human bone marrow stromal cells from the cranial bone and iliac crest.
Cellular therapies represent a new frontier in the treatment of neurological diseases. Accumulating evidence from preclinical studies of animal models suggests that mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, are an effective therapy for neurological diseases. In this study, we established human MSC lines from both cranial bone marrow (cBMMSCs) and iliac crest bone marrow (iBMMSCs) from the same donors and found that cBMMSCs show higher expression of neural crest-associated genes than iBMMSCs. Moreover, as observed in both mRNA and protein assays, neurogenic-induced cells from cBMMSCs expressed significantly higher levels of neural markers, such as NESTIN, SLUG, SOX9, and TWIST, than those from iBMMSCs. Thus, cBMMSCs showed a greater tendency than iBMMSCs to differentiate into neuron-like cells.


Differential changes in the pharmacokinetics of doxorubicin in diethylnitrosamine-induced hepatocarcinoma model rats.
Hepatocellular carcinoma (HCC) is a malignancy of liver cells. Recent studies have shown that HCC patients often have changes in the activities of transporters and metabolic enzymes, which can considerably affect drug pharmacokinetics and lead to drug toxicity. Doxorubicin (DOX) has been frequently administered in chemotherapy for HCC, but to our knowledge, the effects of HCC on the pharmacokinetics of DOX are unknown.In the present study, following intravenous administration of DOX in diethylnitrosamine-induced HCC rats, the plasma concentration was determined by a UPLC/MS/MS method. The expression of metabolic enzyme and transporters (p-gp, cbr1 and slc22a16) was analyzed by qRT-PCR and western blot.The results showed that the pharmacokinetic parameters AUC, T1/2, K12 and K21 of DOX were markedly increased, the K10 and CL were significantly decreased in HCC rats. The expression of cbr1 and slc22a16 was markedly decreased, while p-gp was significantly upregulated in HCC rats.These findings suggest that HCC could significantly alter the pharmacokinetic profile of DOX, which may be associated with the decreased expression of cbr1 and slc22a16 rather than the upregulation of p-gp expression.


Assessment of children's exposure to currently used pesticides in wallonia, Belgium.
In spring 2016, a study was carried out to characterize currently used pesticide (CUP) exposure among children living in Wallonia (Belgium). Pesticides were measured in both first morning urine voids of 258 children aged from 9 to 12 years and in ambient air collected close to the children's schools. Out of the 46 pesticides measured in the air, 19 were detected with frequencies varying between 11 % and 100 %, and mean levels ranging from <0.04 to 2.37 ng/m³. Only 3 parent pesticides were found in 1-10% of the urine samples, while all the metabolites analyzed were positively detected at least once. The captan metabolite (THPI) was quantified in 23.5 % of the samples, while 3,5,6-trichloro-2-pyridinol (chlopryrifos metabolite) was detected in all urines with levels ranging from 0.36-38.96 μg/l. 3-phenoxybenzoic acid (3-PBA), trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (t-DCCA) and diethylphosphate were the most abundant pyrethroid metabolites and dialkylphosphate measured. The air inhalation was demonstrated to be a minor route of exposure for the selected CUPs. Statistical regressions highlighted predictors of exposure for some pesticides such like consumption of grey bread, presence of carpets at home or indoor use of pesticides, although no clear source was identified for most of them.


46,XY Disorder of Sex Development due to 17-Beta Hydroxysteroid Dehydrogenase Type 3 Deficiency in an Infant of Greek Origin.
17-beta hydroxysteroid dehydrogenase type 3 (17βHSD-3) enzyme catalyzes the conversion of androstenedione (Δ4) to testosterone (T) in the testes of the developing fetus, thus playing a crucial role in the differentiation of the gonads and in establishing the male sex phenotype. Any mutation in the encoding gene (HSD17B3) can lead to varying degrees of undervirilization of the affected male, ranging from completely undervirilized external female genitalia to predominantly male with micropenis and hypospadias. We present here an infant who was referred to our clinic because of ambiguous genitalia at birth. Gonads were palpable in the inguinal canal bilaterally and no Müllerian structures were identified on pelvic ultrasound. Because of a low T/Δ4 ratio after a human chorionic gonadotropin stimulation test, a tentative diagnosis of 17βHSD-3 deficiency was made which was confirmed after genetic analysis of the HSD17B3 gene of the patient. The molecular analysis identified compound heterozygosity of two previously described mutations and could offer some further validation for the idea of a founder effect for 655-1;G→A mutation in the Greek population.


International Conference on Harmonisation; guidance on S7B Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals; availability. Notice.
The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "S7B Nonclinical Evaluation of the Potential for Delayed Ventricular Repolarization (QT Interval Prolongation) by Human Pharmaceuticals." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes a nonclinical testing strategy for assessing the potential of a test substance to delay ventricular repolarization and includes information concerning nonclinical assays and an integrated risk assessment. The guidance is intended to facilitate the nonclinical assessment of the effects of pharmaceuticals on ventricular repolarization and proarrhythmic risk.


High-purity magnesium screws modulate macrophage polarization during the tendon-bone healing process in the anterior cruciate ligament reconstruction rabbit model.
Magnesium (Mg) screws perform clinical potential in anterior cruciate ligament (ACL) reconstruction, and promote fibrocartilaginous entheses regeneration at the femoral entrance. We aim to prove that high-purity Magnesium (HP Mg) screws modulate macrophage polarization in fibrocartilage interface regeneration both in vitro and in vivo. HP Mg extracts performed good cytocompatibility and significantly promoted M2 macrophage polarization in the flow cytometry and ELISA assays. M2 macrophages stimulated fibrochondrocyte differentiation of co-cultured hBMSCs, and HP Mg extracts had synergistic effect on the process. Then we applied HP Mg screws, with Ti screws as control, in the ACL reconstruction rabbit model. In the histological and immunofluorescence analysis, HP Mg screws inhibited M1 polarization at 2 weeks and highly promoted M2 polarization at 2 and 4 weeks at the tendon-bone interface. Furthermore, regeneration of fibrocartilaginous entheses, rather than the fibrovascular scar interface, was detected in the HP Mg group at 12 weeks. For further mechanism study via RNA-seq detection and WB assays, we found that AKT1 was highly activated in M2 polarization, and HP Mg could stimulate AKT1 expression, rather than AKT2, in the early phase of tendon-bone healing. Our study elucidated macrophage polarization during tendon-bone healing process and emphasized HP Mg on M2 polarization and fibrocartilage interface regeneration via the selective activation of AKT1 and PI3K/AKT pathway.


Lateral asymmetries and thalamic components in far-field somatosensory evoked potentials.
To investigate the neural generators of the subcortical somatosensory evoked potential (SEP) waves we studied the far-field SEPs in 20 normal adults. We stimulated the median nerve at the wrist and used a 40k gain, 25 msec sweep and a 150-3000 Hz bandpass. We recorded SEPs simultaneously over C3' and C4' using a non-cephalic clavicle reference. The following series of six positive waves were found reliably in all subjects: P9, P11, P13, P14, P16 and P17. The P16 and P17 probably arise from the thalamus and/or thalamocortical projections. Recent evidence suggests that the thalamus is not a closed field and thus one should be able to find corresponding waveforms in far-field recordings. We believe that this is a function of the bandpass used and with the above paradigm these components can be reliably recorded. We found significant ipsilateral and contralateral amplitude asymmetries beginning with the negative deflection after P14 and including P16 and P17. The amplitude was greater over the contralateral hemisphere. This suggested that both P13 and P14 are generated prior to decussation of the afferent fibres in the medial lemniscus. Bilateral recording allowed detection of this asymmetry which has not been previously reported as a means of determining the electrophysiological correlates of lateralization.


Facile oxidation of primary amines to nitriles using an oxoammonium salt.
The oxidation of primary amines using a stoichiometric quantity of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) in CH2Cl2-pyridine solvent at room temperature or at gentle reflux affords nitriles in good yield under mild conditions. The mechanism of the oxidation, which has been investigated computationally, involves a hydride transfer from the amine to the oxygen atom of 1 as the rate-limiting step.


Current priorities in health research funding and lack of impact on the number of child deaths per year.
We determined the proportion of research on childhood mortality directed toward better medical technology (i.e., by improving old technology or creating new technology) compared with research on technology delivery and utilization. We also estimated mortality reductions from a research-funding strategy focusing primarily on developing technology compared with one that also focused on delivery and utilization. Ninety-seven percent of grants were for developing new technologies, which could reduce child mortality by 22%. This reduction is one third of what could be achieved if existing technologies were fully utilized. There is a serious discrepancy between current research and the research needed to save children's lives. In addition to increased research on the efficacy of treatment, there is an even greater need for increased research on delivery and use of technology.


Theme of current journal issue: anxiety disorders across the lifespan.
The papers presented in this issue of Anxiety document various aspects of vulnerability to, and consequences of, anxiety disorders in subjects from different periods of the lifespan. Several themes are represented in one or more of these studies, (1) effects of anxiety disorders on quality of life, (2) effects on presentation and outcome of comorbid depression, and (3) the role of learning processes and early experiences, including abuse, attachment disturbances and personality disorders, in the ongoing predilection to anxiety disorders. We encourage clinicians and researchers to take a life course perspective in working with anxiety disorder patients, in order to better understand, prevent and treat these debilitating conditions.


Underutilization of guideline-recommended therapy in patients 80 years and older with peripheral artery diseases.
Background: Ageing is a major cardiovascular risk factor with detrimental changes that culminate in a high atherosclerotic burden. Peripheral artery disease (PAD) is a major manifestation of atherosclerosis with high mortality. Guideline-recommended treatment is essential, however implementation is inadequate. With an ageing society, age-related inequalities are important and have not been elucidated in a high-risk PAD population on a nation-wide scale. We sought to analyse outpatient treatment structures and guideline adherence in treatment of PAD patients older than 80 years. Patients and methods: The study is based on ambulatory claims data comprising 70.1 million statutorily insured patients per year in Germany from 2009 to 2018. We analysed age-related differences in prevalence, pharmacotherapy and specialized outpatient care in PAD patients. Results: Of 17,633,970 PAD patients included, 28% were older than 80 years. PAD prevalence increased between 2008 and 2018 (1.85% vs. 3.14%), with the proportion of older patients increasing by a third (24.4% vs. 31.2%). Octogenarians were undertreated regarding guideline-recommended statin pharmacotherapy compared to younger patients while antiplatelets were prescribed more often (statins 2016: 46.5% vs. 52.4%; antiplatelets 2016 30.6% vs. 29.3%; p<.05). Furthermore, octogenarians received less specialized outpatient care (angiology: 6.4% vs. 9.5%, vascular surgery: 8.1% vs. 11.8%, cardiology: 25.2% vs. 29.2%, p<.05). Conclusions: Our results demonstrate that age-related differences in pharmacotherapy and specialized outpatient care of PAD patients are evident. While overall guideline-recommended outpatient treatment is low, patients 80 years and older are less likely to receive both, leaving age-related health inequalities a challenge of our future.


Self-limiting caries therapy with proteolytic agents.
To determine the extent to which artificial carious dentin can be removed by agents that do not seem to attack sound dentin such as pepsin, trypsin, collagenase and NaOCl, and to evaluate the effect of the enzyme pepsin and a new enzymatic solution SFC-V (pepsin in mild acidic buffer) as a self-limiting caries therapy in deep dentin carious lesions using our new model for artificial dentin caries. Artificial dentin caries was used to investigate different proteolytic agents which have the potential to remove carious tissue. 408 slices of coronal dentin were subjected to a demineralization regime which produces dentin caries very similar to natural lesions: acetic acid (pH 5) or lactic acid (pH 4) were used (7 days). Subsequently, sodium hypochlorite, collagenase, trypsin and pepsin were dissolved each in a suitable buffer and the demineralized dentin was treated for 10 minutes or 24 hours with these solutions. To differentiate the influence of the acidic buffer in case of pepsin, a second experiment was performed. 192 slices were exposed to lactic acid for 1 week. Subsequently the demineralized dentin surfaces were treated with either the enzyme pepsin in its acidic buffer, the acidic buffer alone, and in addition a neutral buffer as a control. In addition a fourth group was added where a new enzyme-based solution SFC-V was used. This second experiment differentiated further the influence of "diffusion enhanced by agitation" versus "diffusion" alone. The application time of the solutions was 3 minutes with and without agitation using a stiff nylon brush. To obtain information on the morphology of the pre- and post-treatment dentin surfaces, high resolution FE-SEM was used. Descriptive statistics were used based on cross tabulation of the morphological criteria. Lactic acid produced demineralized dentin covered with a surface layer removable by proteolytic enzymes while acetic acid produced only demineralized dentin. The amount of tissue removed with the current proteolytic agents ranked as follows: trypsin < pepsin < collagenase < NaOCl. The neutral and the acidic buffers did not affect the surface precipitates while the enzyme pepsin and the solution SFC-V were effective in removing the degraded organic matrix.


Comparison of three rapid methods for detection of antibodies to streptolysin O and DNase B.
Three commercial systems were compared for ability to detect antibodies to streptolysin O (ASO) and DNase B (ADB). Streptozyme (Wampole Laboratories, Cranbury, N.J.) exhibited high sensitivity (100%) for detecting ASO but low sensitivity for ADB (22.2%). The LeapStrep (Organon Teknika, Malvern, Pa.) and Check-Spectra (Diagnostic Technology, Hauppauge, N.Y.) tests had low sensitivities for detecting ASO (35.3 and 21.4%, respectively) and ADB (22.2 and 33.3%, respectively).


[Study of septicemia due to Enterobacter cloacae in a neonatal intensive care unit].
A study was made of Enterobacter cloacae septicemia in 15 newborns in the neonatal intensive care unit (NICU) of the Asahikawa Kosei Hospital from April, 1979 to March, 1996. Their gestational age was 29.7 +/- 4.5 (mean +/- SD) weeks and their birth weight was 1,270 +/- 562 g. The age at the onset of septicemia was 10.3 +/- 7.2 days. Four infants died and the mortality was 26.7%. These infants died within 72 hours after onset of septicemia. Thrombocytopenia (< 50,000/microliter) in the patients who died was significantly more than in the patients who improved (p < 0.05). Antibiotic susceptibilities were determined by the Kirby-Bauer method. Three E. cloacae strains isolated in 1982 were sensitive to ampicillin (ABPC) and cefotaxime (CTX), 4 strains between 1983 and 1984 were resistant to ABPC and were sensitive to CTX, 5 strains between 1985 and 1992 were resistant to ABPC and CTX, and 3 strains between 1993 and 1995 were resistant to ABPC and were sensitive to CTX. These results suggested that the emergence of resistant E. cloacae was related to the use of corresponding antibiotics. Our observations showed that E. cloacae was one of the potential pathogens seen in nosocomial infections which is becoming progressively common in newborns and routine bacteriological surveillance is very important in the NICU.


A community based study on the prevalence and factors affecting smoking in Kampong Jenderam Hilir, Sepang, Selangor.
i) To determine the prevalence of smoking among the community aged 15 and above in Kg. Jenderam Hilir in Sepang District, Selangor state. ii) To determine the relationship between smoking and age, sex, household income and education. iii) To determine the parental and peer influence on smoking in Kg Jenderam Hilir. A study was conducted in Kg. Jenderam Hilir, Sepang. All residents aged 15 years and above from all the 381 households of Kg. Jenderam Hilir were included in this study. A standardized pre-tested structured questionnaire was used in this study. Out of 894 respondents interviewed 69% were males compared to 3.9% of the females (overall 33.6%) reported to have smoked at least once in his/her lifetime. The difference was statistically significant. The mean duration of smoking was 17.7 years. The age at which smoking was first attempted ranged from 4 years to 51 years with a mean of 18.7 years. The mean initiation age for the males was significantly lower as compared to the mean initiation age for the females. The prevalence of current smokers was significantly higher amongst males (52.8%) as compared to the females (1.4%). The prevalence of smoking among current smokers increased with age (p < 0.01). There was no significant difference in the prevalence of smoking by household income and educational level. The mean number of cigarettes smoked by males was significantly higher than the females (p < 0.05). The mean duration of smoking among current smokers was 20 years. There was a significant difference in the level of addiction to smoking and the duration of smoking (p < 0.05). The high level of addiction increased with the duration of smoking (p < 0.05). Sixty five percent of the current smokers reported to have tried to quit smoking while 26% of ever smokers had reported to quit smoking and remained nonsmokers. The quit ratio was calculated to be 26.0%. The quit ratio was 52.6% among those with college or university education. There was a significant difference in the quit ratio by education level (p < 0.01). There was no significant difference in smokers whose parents were smokers as compared to nonsmokers whose parents were smokers. However, there was a significant association between smoking and peer influence (p < 0.01).


Gradient Field Deviation (GFD) Correction Using a Hybrid-Norm Approach With Wavelet Sub-Band Dependent Regularization: Implementation for Radial MRI at 9.4 T.
In magnetic resonance imaging (MRI), system imperfections and eddy currents can cause gradient field deviation (GFD), leading to various image distortions, such as increased noise, ghosting artifacts, and geometric deformation. These distortions can degrade the clinical value of MR images. Generally, non-Cartesian image sequences, such as radial sampling, produce larger gradient deviations than Cartesian sampling, as a result of stronger eddy current-induced gradient delays and phase errors. In this paper, we developed a GFD encoding method to reduce image noise and artifacts for radial MRI. In the proposed method, a hybrid norm (combination of L2 and L1 norms) optimization problem was formed, which incorporated a wavelet sub-band adaptive regularization mechanism. The new approach seeks a regularized solution not only offering corrected images with reduced artifacts and geometric deformation, but also good preservation of anatomical structural details. The new method was evaluated with simulation and experiment at 9.4 T MRI. The results demonstrated that the proposed method can provide over 50% noise reduction and 15% artifact reduction compared with the traditional regridding method, suggesting substantially reduced GFD-induced distortions and improved image quality.


Persistent anxiogenic effects of a single or repeated doses of cocaine and methamphetamine: interactions with endogenous cannabinoid receptor ligands.
As persistent behavioural changes, such as increased anxiety-related behaviours, can be predicted based on the phenomenon of psychostimulant-induced neuronal plasticity, the time course (3-, 5- and 10-day time points) of the effects of both a single and repeated (daily for 7 days) i.p. administrations of cocaine (COC) and methamphetamine (MA) on anxiety-related behavioural symptoms in the elevated plus-maze test were examined in mice. Furthermore, based on the reported interactions between brain dopamine versus cannabinoid (CB) receptors and the contribution of CB receptors to the occurrence of persistent anxiety-related behavioural symptoms, the interactions of the agonist CP 55940 (CP) and the endogenous ligands anandamide (arachidonylethanolamide: AEA), 2-arachidonylglycerol (ARA), N-arachidonyldopamine (NADA), noladin ether (NL), and virodhamine (VA) with the COC- or MA-induced anxiety-related behaviours were also studied. In both an acute experiment using a single COC (30 mg/kg) or MA (4 mg/kg) dose and a chronic experiment using repeated COC (15 mg/kg) or MA (2 mg/kg) doses, anxiety-related behavioural symptoms were observed similarly at 3- and 5-day time points, but disappeared at the 10-day time point. Among the CB ligands, the agonists CP, AEA, ARA, NADA, and NL provided strong protective effects against each parameter at 3- and 5-day time points. Therefore, it was concluded that both COC and MA caused persistent anxiety-related behavioural symptoms following both a single and repeated treatments. Since these anxiogenic effects were attenuated by the endogenous CB agonists, the involvement of brain CB receptors was suspected.


Interruption study of viremia of patients with hemorrhagic fever with renal syndrome in the febrile phase.
Kinetic changes of viremia were observed in 287 cases of hemorrhagic fever with renal syndrome (HFRS) in whom ribavirin was administered with double blind random control studied by means of virus isolation, indirect immunofluorescence assay and enzyme-linked immunosorbent assay. The positive rate of viremia was 79.7% (Sp = 3%) and positive rate of HERS IgM was 85% (Sp = 3.1%) before treatment. Viremia could be interrupted by ribavirin as in the ribavirin treated group, the viremia positive rate decreased, duration of viremia was shortened, viral antigen products, virus titer and HFRS IgG antibody level were reduced as compared with the control group. This showed that viremia was very frequent in patients in the febrile phase and ribavirin is an effective antiviral drug in HFRS during the febrile phase. Dosage and course of treatment of this drug are discussed.


Allergic contact dermatitis to methylprednisolone aceponate in a topical corticosteroid.
A 42-year-old registered nurse presented with a recurrent history of multifactorial hand dermatitis, which had ceased to respond to the topical corticosteroid that she was using. Patch testing revealed strong reactions to both Advantan Fatty Ointment (Commonwealth Serum Laboratories, Melbourne, Australia), and its active ingredient, methylprednisolone aceponate. Methylprednisolone aceponate is one of the more sensitizing topical corticosteroids and is becoming increasingly recognized as a significant allergen.


Cellular and humoral mechanisms of immune tolerance in immediate-type allergy induced by specific immunotherapy.
The management of immediate-type allergy (ITA) is based on allergen avoidance, symptomatic pharmacological therapy and specific immunotherapy (SIT). Among these, SIT presents the only curative treatment. The efficacy of SIT in the treatment of IgE-mediated ITA has been proven in numerous clinical studies and is well established. This review discusses the relevance of immunoregulative humoral and cellular mechanisms leading to immune tolerance in ITA. Special focus is placed on the role of antibodies potentially interfering with the IgE-mediated immune reaction and regulatory T (T reg) cells including their immunosuppressive cytokines, which play a critical role in shifting the T helper 2 cell-driven allergic immune response towards allergen tolerance. Distinct subsets of constitutive and inducible T reg cells have been identified inhibiting the activation of allergen-specific effector T cells via cell contact- or cytokine-dependent suppression. Current research suggests that both inducible interleukin-10-producing CD4+ T reg cells and naturally occurring CD4+CD25+ T reg cells actively control allergic responses and that the disturbance of their function or number may contribute to the development or progression of allergy. Thus, the fine balance between allergen-specific T helper 2 and T reg cells constitutes a critical factor for the successful treatment of ITA by SIT.


The mechanism of a phosphazene-phosphazane rearrangement.
The phosphazene-phosphazane rearrangement of N3P3Cl5O(CH2)2OC(=O)CMe=CH2 (8) has been examined in detail using one and two dimensional NMR ((31)P, (1)H) spectroscopy and mass spectrometry. The mixed phosphazene-phosphazane [NPCl2]2[N((CH2)2OC(=O)CMe=CH2)P(O)Cl] (14), [NPCl2]2[NHP(O)Cl] (13) and a two ring assembly [NPCl2]2[NP(O{(NPCl2)2(N((CH2)2OC(=O)CMe=CH2)P(O)}] (15) have all been detected in the product mixture. The rate of the rearrangement has been measured at five temperatures by (31)P and (1)H NMR. The reaction is first order in 8 (T1/2 at 111° is 4.65 hours). The activation enthalpy is positive and the activation entropy is negative. A mechanism involving competing intra and inter molecular processes which fits the product distribution and kinetic data has been proposed. Several other methyacrylphosphazenes were examined under the same thermolysis conditions. The rearrangement was observed and the rates obtained in cases where the (CH2)2 spacer unit of the methacrylate was replaced by linear and branched propyl units. The rearrangement was not observed when the methacrylate was appended to a spirocyclic unit, the spacer unit was extended to the n-butyl group and when the methacrylate unit was replaced by a methoxy group. These results are all consistent with the proposed mechanism. This investigation resolves conflicting results previous reported for the rearrangement.


Myeloid-derived suppressor cells and T regulatory cells in tumors: unraveling the dark side of the force.
Important conceptual advances in tumor immunology over the last years have shifted the paradigm from focusing on the malignant cell to the importance of host immune components in the design of successful immunotherapies. The immune system, through sophisticated innate and adaptive immune surveillance mechanisms, inhibits the growth and establishment of tumors. However, despite immune surveillance, tumors still escape and grow, mainly as a result of endowed tumor-induced immunosuppressive circuits. Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) are the major components of these regulatory networks that facilitate tumor immune escape and significantly compromise the efficacy of current immunotherapies. A better understanding of the induction, function, and expansion of these powerful regulatory compartments represents a major challenge on the clinical benefit of current treatments and may foster the design of novel cancer immunotherapies.


Injection of drug residue as a potential risk factor for HCV acquisition among Montréal young injection drug users.
Preparing drugs or medications for injection may leave residues in containers and filters used by injection drug users (IDUs). Little is known about the specific practice of injecting someone else's drug residue as a possible route of HCV transmission. A prospective cohort study of street youth aged 14-23 years old was carried out between July 2001 and December 2005. For this analysis, youth who injected in the six months prior to interview were selected if they were HCV-negative and had completed at least one follow-up visit. Semi-annual visits involved completing an interviewer-administered questionnaire and providing a blood sample for HCV antibody testing. "Sharing behaviors" (any injection preparation behavior that could entail IDUs using injection equipment used by others) including injecting someone else's drug residue were assessed at each interview. Predictors of HCV seroconversion were identified using Cox proportional hazards regression analyses. Two multivariate models were built, one considering sharing behaviors only, and one with cocaine injection forced into it. Of the 175 participants, 60% were male and their mean age was 20.7years old. In both models, residue injection was a predictor of HCV incidence, although with marginal statistical significance. The adjusted hazard ratio estimates were (2.15; 95% CI 0.99-4.67) and (2.11; 95% CI 0.97-4.62) respectively. This epidemiological study underscores the role injection of drug residue may play in HCV transmission among IDUs. In the current context of the worldwide HCV epidemics, this question deserves further investigation.


DNA barcode for identification of immature stages of sand flies (Diptera: Psychodidae) collected from natural breeding sites.
Although phlebotomine sand flies breeding sites have been identified and recorded by several studies, the microhabitats exploited by these insects remain little-known and hard to find. In this context, the difficulty of finding immature stages, and the limited number of taxonomic studies to identify immature stages of phlebotomine sand flies, are considered the major obstacles when attempting a complete inventory of Lutzomyia species. The objective of this study is to validate Cytochrome Oxidase I (Barcode region) as a marker for the identification of immature stages of Lutzomyia species recovered from natural breeding sites in Colombia. Among 142 collected sand flies, 18 immature individuals that did not complete their life cycle were identified to species level through sequencing of the COI gene. Values of K2P genetic distance between 0.002-0.031 allowed the identification of larvae at species level. The bootstrap support values (96%) in the Neighbor-Joining dendrogram were consistent for the majority of the established MOTUS of Lutzomyia atroclavata, Lutzomyia micropyga, Lutzomyia serrana, Lutzomyia cayennensis, Lutzomyia rangeliana, Lutzomyia shannoni and some species of the genus Brumptomyia. The COI gene is validated as a marker for the identification of immature stages of the genus Lutzomyia.


Not all insulin secretagogues sensitize pancreatic islets to recombinant human interleukin 1 beta.
The purpose of this study was to test the influence of different insulin secretagogues on interleukin 1 beta mediated injury to isolated rat pancreatic islets. Islets were exposed to interleukin 1 beta for 6 days. During exposure, beta-cells were stimulated with glucose (11 mmol/l vs 3.3 mmol/l) or with non-nutrients as tolbutamide (250 mumols/l), iso-butyl 1-methyl-xanthine (50 mumols/l), or glucagon (10 mg/l). At 3.3 mmol/l of glucose, 60,000 U/l of interleukin 1 beta caused an inhibition of medium insulin accumulation to 62 +/- 5% of control from 48 h to 6 days of exposure, whereas islet DNA content was unaffected. At 11 mmol/l of glucose, interleukin 1 beta dose-dependently decreased medium insulin accumulation (e.g. 60,000 U/l of interleukin 1 beta, 12 +/- 3% of control) and islet content of DNA (60,000 U/l of interleukin 1 beta, 60 +/- 8% of control). During beta-cell stimulation with tolbutamide, interleukin 1 beta caused inhibition of insulin accumulation to 36 +/- 9% of control. In contrast, on islets stimulated with iso-butyl 1-methyl-xanthine or glucagon, the effects of interleukin 1 beta were equivalent to those on non-stimulated islets. These differences were paralleled by differences in the interleukin 1 beta effect on islet morphology. In conclusion, high beta-cell activity (as measured by islet insulin release) may increase islet susceptibility to interleukin 1 beta, however, depending upon the intracellular pathway through which insulin secretion is activated.


Spectroscopic evaluation of three different gratings used for a flat-field extreme ultraviolet spectrometer to monitor Delta n=1 transitions from medium-Z impurities in 10-30 A.
Spectral characteristics of varied line spacing 2400 grooves/mm gratings used for a flat-field extreme ultraviolet spectrometer have been evaluated to monitor Delta n=1 (n=2-3) transitions from medium-Z impurities in 10-30 A, where many spectral lines from metallic impurities closely exist. For this purpose emission spectra of the Delta n=1 transitions from partially L-shell-ionized Ti and Fe have been measured in large helical device. At first, a ruled and a holographic grating were utilized for the comparative study. Both gratings suppressed higher order light effectively but spectral sensitivity was much higher for the holographic grating. The ruled grating, however, attained better spectral resolution (0.083 A at 18.97 A) in the 10-100 A range compared to that (0.130 A) of the holographic grating. After that a recently developed new holographic grating with different laminar shapes and line spacings has attempted to improve the spectral resolution. As a result, it has considerably improved the spectral resolution in the 10-30 A range, i.e., approximately 0.090 A. However, it is found that the experimentally obtained spectral resolution is quit poor compared to the computationally simulated one, suggesting a technical difficulty in manufacturing exactly the varied line spacing of the holographic grating at such a short wavelength range.


Plasma thrombin activatable fibrinolysis inhibitor and tissue factor pathway inhibitor changes following sepsis.
Sepsis-induced systemic inflammation results in coagulation abnormalities that may be different in gram-positive and gram-negative infections. We used ciprofloxacin to induce a predominantly gram-positive Enterococcus faecalis polymicrobial sepsis in rats. Ciprofloxacin-untreated rats exhibited a predominantly gram-negative polymicrobial sepsis. Rats were subjected to 30% body surface area burn (B), cecal ligation puncture (CLP) with a 22-gauge needle, and B + CLP. Ciprofloxacin-treated B + CLP rats showed a significant decrease in plasma thrombin activatable fibrinolysis inhibitor (TAFI) levels compared with sham rats. However, plasma tissue factor pathway inhibitor (TFPI) levels decreased significantly in B, CLP, and B + CLP groups compared with sham rats. The ciprofloxacin-untreated group showed a significant decrease in plasma TAFI levels in CLP and B + CLP and plasma TFPI levels decreased in all 3 groups compared with sham rats. Histological changes in the liver and kidney included vascular congestion and parenchyma bleed following B + CLP in ciprofloxacin-untreated rats. These results suggest that plasma TAFI and TFPI levels differ depending on the type of bacteria involved in the septic process.


Odocoileus hemionus deer adenovirus is related to the members of Atadenovirus genus.
The Odocoileus hemionus deer adenovirus (OdAdV-1) causes systemic and local vasculitis and proves extremely lethal for mule deer. To characterize the virus, part of the genome flanking the fiber gene was cloned and sequenced. The sequence revealed two open-reading frames that mapped to pVIII hexon-associated protein precursor and fiber protein of several other adenoviruses. The highest amino acid homology for pVIII and fiber was found with the members of the proposed Atadenovirus genus: ovine adenovirus isolate 287 (OAdV-287), bovine adenovirus 4 (BAdV-4) and duck adenovirus 1 (DAdV-1). The homology with bovine adenovirus type 3 (BAdV-3) proved low. The E3 region was not found between the gene for pVIII and fiber. These data suggest that OdAdV-1 is a member of the Atadenovirus genus.


Publication bias in animal research presented at the 2008 Society of Critical Care Medicine Conference.
To determine a direct measure of publication bias by determining subsequent full-paper publication (P) of studies reported in animal research abstracts presented at an international conference (A). We selected 100 random (using a random-number generator) A from the 2008 Society of Critical Care Medicine Conference. Using a data collection form and study manual, we recorded methodology and result variables from A. We searched PubMed and EMBASE to June 2015, and DOAJ and Google Scholar to May 2017 to screen for subsequent P. Methodology and result variables were recorded from P to determine changes in reporting from A. Predictors of P were examined using Fisher's Exact Test. 62% (95% CI 52-71%) of studies described in A were subsequently P after a median 19 [IQR 9-33.3] months from conference presentation. Reporting of studies in A was of low quality: randomized 27% (the method of randomization and allocation concealment not described), blinded 0%, sample-size calculation stated 0%, specifying the primary outcome 26%, numbers given with denominators 6%, and stating number of animals used 47%. Only being an orally presented (vs. poster presented) A (14/16 vs. 48/84, p = 0.025) predicted P. Reporting of studies in P was of poor quality: randomized 39% (the method of randomization and allocation concealment not described), likely blinded 6%, primary outcome specified 5%, sample size calculation stated 0%, numbers given with denominators 34%, and number of animals used stated 56%. Changes in reporting from A to P occurred: from non-randomized to randomized 19%, from non-blinded to blinded 6%, from negative to positive outcomes 8%, from having to not having a stated primary outcome 16%, and from non-statistically to statistically significant findings 37%. Post-hoc, using publication data, P was predicted by having positive outcomes (published 62/62, unpublished 33/38; p = 0.003), or statistically significant results (published 58/62, unpublished 20/38; p < 0.001). Only 62% (95% CI 52-71%) of animal research A are subsequently P; this was predicted by oral presentation of the A, finally having positive outcomes, and finally having statistically significant results. Publication bias is prevalent in critical care animal research.


Chemistry Is Dead. Long Live Chemistry!
Chemistry, once king of fluorescence microscopy, was usurped by the field of fluorescent proteins. The increased demands of modern microscopy techniques on the "photon budget" require better and brighter fluorophores, causing a renewed interest in synthetic dyes. Here, we review the recent advances in biochemistry, protein engineering, and organic synthesis that have allowed a triumphant return of chemical fluorophores to modern biological imaging.


Do we need more drugs for chronic myeloid leukemia?
The introduction of protein tyrosine kinase inhibitors (TKIs) in 1998 transformed the management of chronic myeloid leukemia (CML), leading to significantly reduced mortality and improved 5 year survival rates. However, the CML community is faced with several clinical issues that need to be addressed. Ten to 15% of CML patients are diagnosed in advanced phase, and small numbers of chronic phase (CP) cases experience disease progression each year during treatment. For these patients, TKIs induce only transient responses and alternative treatment strategies are urgently required. Depending on choice of first line TKI, approximately 30% of CML CP cases show suboptimal responses, due to a combination of poor compliance, drug intolerance, and drug resistance, with approximately 50% of TKI-resistance caused by kinase domain mutations and the remainder due to unknown mechanisms. Finally, the chance of successful treatment discontinuation is on the order of only 10-20% related to disease persistence. Disease persistence is a poorly understood phenomenon; all CML patients have functional Philadelphia positive (Ph+) stem and progenitor cells in their bone marrows and continue to express BCR-ABL1 by DNA PCR, even when in very deep remission and following treatment discontinuation. What controls the maintenance of these persisting cells, whether it is necessary to fully eradicate the malignant clone to achieve cure, and how that might be approached therapeutically are open questions.


[FTIR and 13C NMR Analysis of Dissolved Organic Matter (DOM) in the Treatment Process of Tannery Wastewater].
Nowadays, the wastewater quantity discharged yearly from tannery industry is around 0. 2 billion t in China. The contaminants of tannery wastewater include macromolecular organic matters, such as grease, fur scraps and collagen, and the alkaline wastewater appears to be of high content of salt and COD. The quality of tannery wastewater is monitored strictly among all kinds of industry wastewater. In the treatment process of tannery wastewater, the quality of inlet and outlet water is generally analyzed. In fact, the transformation behavior of contaminants should be additionally checked to optimize the treatment conditions. Dissolved organic matter (DOM) is commonly existed in water-bodies and helpful to understand the physicochemical characteristics, while the related work should be further studied on tannery wastewater. The approaches of elemental analysis, thermal gravimetric analysis (TG), Fourier infrared spectroscopy (FTIR) and 13C nuclear magnetic resonance (13C NMR) were used to reveal the characteristics of DOM in the treatment process of tannery wastewater. The results showed the carbon content of DOM samples increased gradually, atomic ratios of H/C increased firstly and then decreased, indicating the organic matters were decomposed into chain structures firstly, finally forming the component hard to degraded. The pyrolysis process of DOM mainly proceeded in the regions of 110~530 °C (aliphatic compound, protein, etc. ) and 530~800 °C (aromatic ring, single bond of C-C, etc. ). The functional groups of DOM included -OH, -NH2, C=O and so on, and the aromatic substances were detected, shown from FTIR figures, in the later period of the reaction, caused by the metabolism effect of micro-organism. The content of alkoxy-C increased to the maximum in the second biochemical pond, and the minimum content of aromatic-C appeared in the second biochemical pond, suggesting the transformation behavior of carbon functional groups. The investigation on DOM in tannery wastewater is significant to understand the purification mechanism of contaminants in tannery wastewater.


Launaea taraxacifolia (Willd.) Amin ex C. Jeffrey inhibits oxidative damage and econucleotidase followed by increased cellular ATP in testicular cells of rats exposed to metropolitan polluted river water.
Humans are directly/indirectly exposed to hazardous chemicals from the aquatic environment. We investigated the protection of the Launea taraxacifolia methanolic extract (LTME) on the hydroxyl steroid dehydrogenases [(∆5-3β-hydroxyl steroid dehydrogenase (∆5-3β-HSD) and the ∆5-17β-hydroxyl steroid dehydrogenase (∆5-17β-HSD), testicular 5'-nucleotidase and lactate dehydrogenase (LDH)] activities as well as the key indicators of oxidative stress in germinal epithelial cells of rats induced with surulere polluted river water (SPRW). The animals were divided into six groups (n=8). Group I was given 1 mL of distilled water only, Group II received 1 mL of SPRW only, Group III received 200 mg/kg LTME before+1 mL of SPRW after, Group IV received 200 mg/kg LTME+1 mL of SPRW, Group V received 1 mL of SPRW before+200 mg/kg LTME after and Group VI received 200 mg/kg LTME only. The treatment was done via oral administration for 28 days. The HPLC results showed the abundance of quercetin and quercitrin. The SPRW increased 5'-nucleotidase with the concomitant decrease of ∆5-3β-HSD, ∆5-17β-HSD and LDH activities in rats exposed in relation to the control. Similarly, the administration of the SPRW caused a systemic oxidative damage along with adverse histopathological changes in germinal epithelial cells. Interestingly, these alterations were differentially reversed by LTME via the elevation of steroidogenic enzymes and cellular ATP.


Diffuse cavernous hemangioma of the penis, scrotum, perineum, and rectum--a rare tumor.
Hemangiomas are benign lesions that occur in any part of the body. Genital hemangioma involving the entire penis and scrotum are extremely rare. More rarely they can extend in to the pelvis making preoperative imaging imperative and decisive in treatment. Very few cases have been reported in the medical literature. Hereby, a rare cavernous hemangioma that involves the entire penis, scrotum and extends into perineum and rectum in an 18-year-old male is presented with review of literature.