Immunoinflammatory and oxidative alterations in subjects with schizophrenia under clozapine: A meta-analysis.
Clozapine presents immunoregulatory properties not well understood. To address this issue, we performed this systematic review to evaluate the immune alterations induced by clozapine and its relationship with the drug's clinical response and compare it with other antipsychotics. Our systematic review has selected nineteen studies meeting the inclusion criteria, from which eleven were included in the meta-analysis, totalizing 689 subjects distributed over three different comparisons. The results revealed that clozapine treatment activates the compensatory immune-regulatory system (CIRS) (Hedges's g = +1.049; CI +0.62 - +1.47, p < 0.001) but has no effects on the immune-Inflammatory Response System (IRS) (Hedges's g= -0.27; CI -1.76 - +1.22, p = 0.71), M1 macrophage (Hedges's g= -0.32; CI -1.78 - +1.14, p = 0.65) and Th1 (Hedge's g = 0.86; CI -0.93 - +1.814, p = 0.07) profiles. Comparing clozapine-treated patients with other anti-psychotics-treated, plasma levels of interleukin (IL)-6 were greater in the clozapine group (Hedge's g = 0.75; CI 0.35 - 1.15, p<0.001). In addition, higher IL-6 plasma levels after four weeks of clozapine treatment were related to the development of clozapine-induced fever; however, IL-6 levels recovered to baseline in 6-10 weeks due to an unexplained compensatory mechanism. In conclusion, our results show that clozapine treatment causes a time-dependent mixed immune profile characterized by increased IL-6 levels and CIRS activation, which may contribute to this drug mechanism of action and adverse effects. Future studies must be designed to investigate the relationship between clozapine-induced immune alterations and symptom remission, treatment resistance, and adverse effects, given the importance of this drug for treating resistant schizophrenia.


Overexpression of PtoMYB115 improves lignocellulose recalcitrance to enhance biomass digestibility and bioethanol yield by specifically regulating lignin biosynthesis in transgenic poplar.
Woody plants provide the most abundant biomass resource that is convertible for biofuels. Since lignin is a crucial recalcitrant factor against lignocellulose hydrolysis, genetic engineering of lignin biosynthesis is considered as a promising solution. Many MYB transcription factors have been identified to involve in the regulation of cell wall formation or phenylpropanoid pathway. In a previous study, we identified that PtoMYB115 contributes to the regulation of proanthocyanidin pathway, however, little is known about its role in lignocellulose biosynthesis and biomass saccharification in poplar. Here, we detected the changes of cell wall features and examined biomass enzymatic saccharification for bioethanol production under various chemical pretreatments in PtoMYB115 transgenic plants. We reported that PtoMYB115 might specifically regulate lignin biosynthesis to affect xylem development. Overexpression of PtoMYB115 altered lignin biosynthetic gene expression, resulting in reduced lignin deposition, raised S/G and beta-O-4 linkage, resulting in a significant reduction in cellulase adsorption with lignin and an increment in cellulose accessibility. These alterations consequently improved lignocellulose recalcitrance for significantly enhanced biomass saccharification and bioethanol yield in the PtoMYB115-OE transgenic lines. In contrast, the knockout of PtoMYB115 by CRISPR/Cas9 showed reduced woody utilization under various chemical pretreatments. This study shows that PtoMYB115 plays an important role in specifically regulating lignin biosynthesis and improving lignocellulose features. The enhanced biomass saccharification and bioethanol yield in the PtoMYB115-OE lines suggests that PtoMYB115 is a candidate gene for genetic modification to facilitate the utilization of biomass.


Prognostic value of nomogram based on pre-treatment inflammatory markers in patients with pulmonary-only synchronous metastases from colorectal cancer.
The inflammatory markers were important factors affecting proliferation, invasiveness and metastasis of tumors. However, the prognostic value of inflammatory markers and related nomogram in patients with pulmonary-only synchronous metastases (POSM) from colorectal cancer has not been reported. A total of 98 POSM patients undergoing resection of colorectal cancer were included. The Kaplan-Meier survival analysis and Cox regression analysis were used to estimate the overall survival (OS) and progression-free survival (PFS). The nomogram was built based on multivariate Cox analysis model and evaluated by calibration curve, concordance index (C-index) and receiver operating characteristics (ROC). The multivariate analysis showed that neutrophil-to-lymphocyte ratio (NLR) was prognostic factor of OS (HR = 2.73, 95%CI: 1.54-4.84) and PFS (HR = 1.78, 95%CI: 1.13-2.82). Elevated alkaline phosphatase (ALP) also was predictor of poor OS (HR = 1.99, 95%CI: 1.12-3.51) and PFS (HR = 2.23, 95%CI: 1.40-3.55). The early N stage and solitary pulmonary metastases had significant survival benefit for OS, while advanced T stage was independently related with worse PFS. Nomograms were consist of above significant risk factors, with C-index of 0.742 for OS and 0.656 for PFS. The calibration curves showed non-significant deviations between predicted and actual probability of OS and PFS. Pre-treatment NLR and ALP were independently associated with OS and PFS in POSM patients. The nomograms involving inflammatory markers and clinicopathological factors were practical in predicting survival, which may help to guide use of therapeutic strategy and cancer surveillance.


Myocardial single-photon emission computed tomographic imaging with technetium 99m tetrofosmin: stress-rest imaging with same-day and separate-day rest imaging.
Technetium 99m tetrofosmin is a new ethylene diphosphine ligand for myocardial perfusion imaging and has unique properties. We have compared stress-rest single-photon emission computed tomographic (SPECT) imaging with 99mTc tetrofosmin with same-day and separate-day rest imaging to detect myocardial perfusion defects. Myocardial SPECT imaging was performed in 22 patients with coronary artery disease who had undergone planar thallium 201 imaging and coronary angiography. Single-day (stress-rest) and separate-day rest 99mTc tetrofosmin SPECT protocols were compared in the same patient. Images were assessed by a blinded panel to identify myocardial infarction, ischemia, or normal scans. Overall sensitivity for identification of patients with coronary artery disease was 86% (19/22) by both same-day stress-rest and separate-day rest protocols with 99mTc tetrofosmin (p = NS). Of a total of 396 segments studied, 107 abnormal segments were identified at exercise and 76 and 81 at the same-day and separate-day rest tests, respectively (p = NS). Same-day stress-rest and separate-day rest 99mTc tetrofosmin SPECT protocols were also useful for detecting individual coronary stenosis with a greater than 50% lesion: 80% of the left anterior descending, 93% of the right coronary, and 75% of the left circumflex coronary arteries were detected. Excellent images were obtained with 99mTc tetrofosmin during both stress and rest. 99mTc tetrofosmin imaging with the same-day stress-rest and separate-day rest imaging protocols have similar diagnostic sensitivities for detection of coronary heart disease.


Biodegradation of bensulphuron-methyl by a novel Penicillium pinophilum strain, BP-H-02.
A fungal strain able to rapidly degrade bensulphuron-methyl (BSM), called BP-H-02, was isolated for the first time from soil that had been contaminated with BSM for several years. BP-H-02 can use BSM as the sole carbon and energy source for growth in a mineral salt medium. Based on morphological and internal transcribed spacer (ITS) analysis, BP-H-02 was identified as Penicillium pinophilum. Under optimal conditions (pH 6.5, temperature 30 °C and 200 mg/L VSSinoculum), more than 87% of the initially added BSM (50mg/L) was degraded after 60 h. Metabolites were identified as 2-amino-4,6-dimethoxypyrimidine and 1-(4,6-dimethoxypyrimidin-2-yl) urea by liquid chromatography-mass spectrometry (LC-MS), and a possible degradation pathway was deduced. In a soil bioremediation experiment, inoculation of soil with BP-H-02 promoted the degradation of BSM more effectively than did the control. These results revealed that BP-H-02 can biodegrade bensulphuron-methyl efficiently and could potentially be used to bioremediate sulphonylurea herbicides contamination.


Effects of bepridil and lidocaine on the intraventricular conduction in acutely ischaemic and infarcted canine myocardium.
Effects of bepridil, an antiarrhythmic and antianginal drug, on intraventricular conduction in acutely ischaemic and infarcted myocardium were examined in anaesthetized dogs, and compared with those of lidocaine. Bepridil at doses of 2 and 5 mg/kg markedly prolonged the conduction time of a premature excitation induced by a ventricular stimulation in the infarcted zone. The effect of bepridil was dependent on a coupling time of the stimulation. Bepridil showed a marked effect at a coupling time of 150 ms, while it showed no significant effect at a prolonged coupling time of 1 s. In other words, the effect of bepridil was interval-dependent. Lidocaine showed a similar interval-dependent effect, but the effect of lidocaine at a longer coupling time was less than that of bepridil. The premature stimulation produced severely delayed conduction which resulted in reentrant beats. Bepridil blocked these conductions, thereby preventing reentrant beats. In contrast to the depressant effect of bepridil in the infarcted myocardium, bepridil prevented the prolongation of conduction time during acute ischaemia. The alternation of the ST-T complex during acute ischaemia which is also an important arrhythmogenic factor was also attenuated by bepridil. Contrary to bepridil, lidocaine significantly enhanced the conduction delay and the alternation in the ST-T complex. In conclusion, bepridil as well as lidocaine showed an interval-dependent depression of the conduction in the infarcted zone of the heart, whereas during acute ischaemia bepridil in contrast to lidocaine attenuated the conduction delay and ST-T alternans.


Cerebral information processing estimated by unpredictability of the EEG.
Processing of complex information by the brain desynchronizes neuronal cells and therefore increases the unpredictability of the EEG, rather than its amplitude or power. A model of this mechanism describes the EEG as being composed of both an unpredictable fraction and a fraction that can be predicted from the past EEG. The model realistically simulates EEG of several behavioural states and suggests a simple algorithm for the computation of EEG predictability (values between 0% and 100%). Applications in sleep analysis and event-related desynchronization demonstrated that the algorithm is more accurate and artifact-resistant than the usual (spectral) power methods.


Collaboration and conquest: MTD as viewed by voice teacher (singing voice specialist) and speech-language pathologist.
This study was designed as a qualitative case study to demonstrate the process of diagnosis and treatment between a voice team to manage a singer diagnosed with muscular tension dysphonia (MTD). Traditionally, literature suggests that MTD is challenging to treat and little in the literature directly addresses singers with MTD. Data collected included initial medical screening with laryngologist, referral to speech-language pathologist (SLP) specializing in voice disorders among singers, and adjunctive voice training with voice teacher trained in vocology (singing voice specialist or SVS). Initial target goals with SLP included reducing extrinsic laryngeal tension, using a relaxed laryngeal posture, and effective abdominal-diaphragmatic support for all phonation events. Balance of respiratory forces, laryngeal coordination, and use of optimum filtering of the source signal through resonance and articulatory awareness was emphasized. Further work with SVS included three main goals including a lowered breathing pattern to aid in decreasing subglottic air pressure, vertical laryngeal position to lower to allow for a relaxed laryngeal position, and a top-down singing approach to encourage an easier, more balanced registration, and better resonance. Initial results also emphasize the retraining of subject toward a sensory rather than auditory mode of monitoring. Other areas of consideration include singers' training and vocal use, the psychological effects of MTD, the personalities potentially associated with it, and its relationship with stress. Finally, the results emphasize that a positive rapport with the subject and collaboration between all professionals involved in a singer's care are essential for recovery.


Survival rate after resection for bronchial carcinoma.
Among factors influencing long-term survival of patients how had undergone resection for carcinoma of the lung, the most important seems to be the extent of the cancer at the time of resection, determined by histopathological studies of the resected specimen.


Discovery of 3,7-dimethoxyflavone that inhibits liver fibrosis based on dual mechanisms of antioxidant and inhibitor of activated hepatic stellate cell.
The important pathway toward liver fibrosis is the TGF-β1-induced activation of hepatic stellate cells (HSCs). To discover chemicals to inhibit liver fibrosis, we screened 3000 chemicals using cell array system where human HSCs line LX2 cells are activated with TGF-β1. We discovered 3,7-dimethoxyflavone (3,7-DMF) as a chemical to inhibit TGF-β1-induced activation of HSCs. In the thioacetamide (TAA)-induced mouse liver fibrosis model, 3,7-DMF treatment via intraperitoneal or oral administration prevented liver fibrosis as well as reversed the established fibrosis in the separate experiments. It also reduced liver enzyme elevation, suggesting protective effect on hepatocytes because it has antioxidant effect. Treatment with 3,7-DMF induced antioxidant genes, quenches ROS away, and improved the hepatocyte condition that was impaired by H2O2 as reflected by restoration of HNF-4α and albumin. In the TAA-mouse liver injury model also, TAA significantly increased ROS in the liver which led to decrease of albumin and nuclear expression of HNF-4α, increase of TGF-β1 and hepatocytes death, accumulation of lipid, and extra-nuclear localization of HMGB1. Treatment of 3,7-DMF normalized all these pathologic findings and prevented or resolved liver fibrosis. In conclusion, we discovered 3,7-DMF that inhibits liver fibrosis based on dual actions; antioxidant and inhibitor of TGF-β1-induced activation of HSCs.


DCC: a Swiss army knife for structure factor analysis and validation.
Since 2008, X-ray structure depositions to the Protein Data Bank archive (PDB) have required submission of experimental data in the form of structure factor files. RCSB PDB has developed the program DCC to allow worldwide PDB (wwPDB; http://wwpdb.org) biocurators, using a single command-line program, to invoke a number of third-party software packages to compare the model file with the experimental data. DCC functionality includes structure factor validation, electron-density map generation and slicing, local electron-density analysis, and residual B factor analysis. DCC outputs a summary containing various crystallographic statistics in PDBx/mmCIF format for use in automatic data processing and archiving pipelines.


Morphometric cytochemistry of diminution of catalase-containing peroxisomes in copper-loaded liver.
The density of hepatocellular catalase-containing peroxisomes was quantified, utilizing a computer-aided image analysing technique, on 1-micron thick diaminobenzidine-stained sections. Hepatic copper accumulation following intraperitoneal injection of cupric chloride resulted in a dose-dependent reduction in the density of catalase-containing peroxisomes. A significant correlation between the density of peroxisomes and the activity of hepatic catalase indicated that computer-aided image analysis of peroxisomes stained by the diaminobenzidine technique provided a useful estimate of catalase activity in liver injured by copper. Slight treatment-related differences in the mean diameter of peroxisomes were detected in high-dose but not low-dose rats.


The mitochondrial fission receptor Mff selectively recruits oligomerized Drp1.
Dynamin-related protein 1 (Drp1) is the GTP-hydrolyzing mechanoenzyme that catalyzes mitochondrial fission in the cell. Residing in the cytosol as dimers and tetramers, Drp1 is recruited by receptors on the mitochondrial outer membrane, where it further assembles into a helical ring that drives division via GTP-dependent constriction. The Drp1 receptor Mff is a major regulator of mitochondrial fission, and its overexpression results in increased fission. In contrast, the alternative Drp1 receptors MiD51 and MiD49 appear to recruit inactive forms of Drp1, because their overexpression inhibits fission. Using genetic and biochemical assays, we studied the interaction of Drp1 with Mff. We show that the insert B region of Drp1 inhibits Mff-Drp1 interactions, such that recombinant Drp1 mutants lacking insert B form a stable complex with Mff. Mff cannot bind to assembly-deficient mutants of Drp1, suggesting that Mff selectively interacts with higher-order complexes of Drp1. In contrast, the alternative Drp1 receptors MiD51 and MiD49 can recruit Drp1 dimers. Therefore Drp1 recruitment by Mff versus MiD51 and MiD49 may result in different outcomes because they recruit different subpopulations of Drp1 from the cytosol.


Correspondence to: Estimating the full health and economic benefits of current and future influenza vaccines.
We recently published an article in BMC Medicine looking at the potential health and economic impact of paediatric vaccination using next-generation influenza vaccines in Kenya: a modelling study. In their commentary on our article, Lafond et al. highlight the potential importance of the wider benefits of vaccination on cost-effectiveness. Whilst we agree with many points raised in the commentary, we think it raises further interesting discussion points, specifically around model complexity, model assumptions and data availability. These points are both relevant to this manuscript but have wider implications for vaccine cost-effectiveness studies.


The adhesion of clots in wounds contributes to hemostasis and can be enhanced by coagulation factor XIII.
The adhesion of blood clots to wounds is necessary to seal injured vasculature and achieve hemostasis. However, it has not been specifically tested if adhesive failure of clots is a major contributor to rebleeding and what mechanisms prevent clot delamination. Here, we quantified the contribution of adhesive and cohesive failure to rebleeding in a rat model of femoral artery injury, and identified mechanisms that contribute to the adhesive strength of bulk clots in a lap-shear test in vitro. In the rat bleeding model, the frequency of clot failures correlated positively with blood loss (R = 0.81, p = 0.014) and negatively with survival time (R = - 0.89, p = 0.0030), with adhesive failures accounting for 51 ± 14% of rebleeds. In vitro, adhesion depended on fibrinogen and coagulation factor XIII (FXIII), and supraphysiological FXIII improved adhesive strength. Furthermore, when exogenous FXIII was topically applied into the wound pocket of rats, eleven adhesive failures occurred between eight rats, compared to seventeen adhesive failures between eight untreated rats, whereas the number of cohesive failures remained the same at sixteen in both groups. In conclusion, rebleeding from both adhesive and cohesive failure of clots decreases survival from hemorrhage in vivo. Both endogenous and exogenous FXIII improves the adhesive strength of clots.


rDNA array length is a major determinant of replicative lifespan in budding yeast.
The complex processes and interactions that regulate aging and determine lifespan are not fully defined for any organism. Here, taking advantage of recent technological advances in studying aging in budding yeast, we discovered a previously unappreciated relationship between the number of copies of the ribosomal RNA gene present in its chromosomal array and replicative lifespan (RLS). Specifically, the chromosomal ribosomal DNA (rDNA) copy number (rDNA CN) positively correlated with RLS and this interaction explained over 70% of variability in RLS among a series of wild-type strains. In strains with low rDNA CN, SIR2 expression was attenuated and extrachromosomal rDNA circle (ERC) accumulation was increased, leading to shorter lifespan. Suppressing ERC formation by deletion of FOB1 eliminated the relationship between rDNA CN and RLS. These data suggest that previously identified rDNA CN regulatory mechanisms limit lifespan. Importantly, the RLSs of reported lifespan-enhancing mutations were significantly impacted by rDNA CN, suggesting that changes in rDNA CN might explain the magnitude of some of those reported effects. We propose that because rDNA CN is modulated by environmental, genetic, and stochastic factors, considering rDNA CN is a prerequisite for accurate interpretation of lifespan data.


Darwinian aspects of molecular evolution at sublinear propagation rates.
Mean fitness is non-decreasing in the symmetry sector of the frequency trajectory followed in competitive replication at sublinear propagation rates (parabolic time course). This sector contains the pairwise symmetric distribution of species frequencies and its neighboring states, and represents at least half the possible states of an evolving sublinear system. States is the non-symmetry sector produce a negative rate of change in mean fitness. The heterogeneous steady state attained in a finite sublinear system is destabilized by formation of a variant with above-threshold fitness. Evolution in the post-steady-state interval elevates the fitness threshold for coexistence. Contrary to the proposition that 'parabolic growth invariably results in the survival of all competing species', only species with sufficient fitness to avoid subthreshold fitness survive.


Time-multiplexed multislice inversion-recovery techniques for NMR imaging.
Multislice imaging techniques effectively applicable to inversion-recovery (IR) imaging are developed and applied to human imaging. These new multislice IR imaging sequences employ the time-multiplexing (TM) technique conventionally used in the slice-by-slice saturation-recovery (SR) imaging. Two new time-multiplexed multislice (TMM) IR imaging sequences are proposed and some of the experimental results obtained with the methods are presented.


Effects of item and rater characteristics on checklist recording: what should we look for?
Examinations based on using standardised patients (SPs) commonly use checklist recordings to evaluate students' clinical performance. This paper examines whether and to what extent item and rater characteristics affect the reliability of history checklist recording in an SP-based assessment. Checklist items were reviewed for the presence or absence of 5 item characteristics and a 2-point versus 3-point scoring scale. Agreement between checklist recordings obtained from SPs and clinician-examiners (CEs) were compared by item characteristics, scoring scale and CEs' level of involvement in the assessment. Based on 3179 pairs of recordings, the overall percentage of agreement between SPs and CEs was 83% (kappa = 0.64). Agreement was significantly higher for items scored on a 2-point than on a 3-point scale, and when the CE was also the author and the trainer of the station. After controlling for other factors, item characteristics were only marginally associated with level of interrater agreement. This study suggests that attention should be paid to specific aspects of checklist development and checklist recording training when an SP or CE is used as recorder.


Differential Diagnosis of Mimicking Tumor Discs Using Coronal Magnetic Resonance Imaging of Three-Dimensional Fast-Field Echo with Water-Selective Excitation: A Single Center Retrospective Study.
As disc fragment completely loses contact with the parent disc and can migrate in all directions of the epidural space, making it appear similar to schwannoma, it is fairly difficult to make a definitive diagnosis for mimicking tumor discs. The aim of this research is to differentially diagnose mimicking tumor discs and schwannomas using coronal magnetic resonance imaging (MRI) of three-dimensional fast-field echo with water-selective excitation (CMRI). Among 76 patients (38 men and 38 women; mean age, 52.88 ± 15.80 [range, 18-78 years]) who were retrospectively examined in this study, 38 were primarily diagnosed with schwannomas and pathologically diagnosed with mimicking tumor discs after surgery, and 38 were primarily diagnosed with neurogenic tumors and pathologically diagnosed with schwannomas after surgery. Open surgery was performed in all the patients between March 2016 and April 2020. The preliminary diagnosis of all patients was considered an intraspinal tumor based on conventional two-dimensional MRI sequences. After open surgery, the final diagnosis was confirmed to mimic a tumor disc or schwannoma based on postoperative pathology reports. The sensitivity, specificity, and reliability of CMRI and conventional MRI for identifying mimicking tumor discs and schwannomas were compared. Chi-square and McNemar tests were used for statistical analyses. Symptoms were considerably relieved in all the patients after surgery. Seven patients had grade 1 extensor digitorum longus, triceps surae, or quadriceps femoris muscle strength prior to surgery. No nerve root injury was observed in any of the patients. CMRI showed significantly higher sensitivity (94.74%) and specificity (94.74%) than conventional MRI (71.05% and 92.11%, respectively; p = 0.012 < 0.05, and p = 1 > 0.05, respectively) for differential identification between mimicking tumor discs and schwannomas. Moreover, CMRI showed a higher reliability (kappa value = 0.787) than conventional MRI (kappa value = 0.374). CMRI is a better non-invasive technology for the identification of intraspinal lesions, especially for differentiating between mimicking tumor discs and schwannomas.


Cytotoxicity and teratogenicity of chlorhexidine diacetate released from hollow nylon fibres.
Intra-uterine contraceptive devices are associated with an increased incidence of pelvic infections, possible due to the introduction of vaginal bacteria into the uterus at insertion. One potential means to overcome this problem is the use of a device which releases the antimicrobial agent chlorhexidine although such an approach carries with it the risk of adverse effects on the endometrium and, possibly, teratogenic effects. Cultured monolayers of endometrial cells were used to assess the cytotoxicity of both chlorhexidine and chlorhexidine-releasing devices. The results indicated that the agent is toxic at concentrations of 1 microg mL(-1) and that the devices potentiated the toxicity. When the devices were tested in a guinea-pig model, endometrial damage was seen only at the high dose of chlorhexidine, suggesting that there is greater distribution of chlorhexidine in-vivo. Assessment of the teratogenic effects of chlorhexidine in rat embryonic limb bud tissue cells in-vitro showed that the foetal cells were highly susceptible to the toxic effects of chlorhexidine, but that there was no evidence of teratogenicity. Overall, the findings suggest that chlorhexidine-releasing devices may be a safe means of reducing infections related to intra-uterine devices, but that the chlorhexidine may have a toxic effect on foetal cells.


Diet of a sigmodontine rodent assemblage in a Peruvian montane forest.
Knowledge of feeding habits of small rodents is necessary for understanding food webs, trophic structure, and plant-animal interactions in Neotropical forests. Despite several studies that have investigated community structure and feeding behavior of rodents, large gaps remain in our understanding of their guild occupancy. Our objective was to investigate the diets of 7 species of small (< 100g) sympatric sigmodontine rodents in a high (3,500 m) Andean montane rainforest in Peru. We qualitatively and quantitatively assessed diet items in fecal samples from livetrapped rodents from 2009 to 2012. Frequency data for 4 diet categories indicated that all 7 species of rodents contained 4 diet categories in fecal samples: arthropods (88%), remains of leaves and fibers from plants (61%), intact seeds (with or without fruit pulp; 50%), and mycorrhizal spores (45%). Omnivory was found to be a strategy used by all species, although contingency table analysis revealed significant differences among and within species in diet categories. Cluster analysis showed 2 main groupings: that of the Thomasomys spp. plus Calomys sorellus group which included high amounts of intact seeds and plant parts in their fecal samples, and those of the genera Akodon, Microryzomys, Oligoryzomys, which included a greater proportion of arthropods in their fecal samples, but still consumed substantial amounts of fruit and plant parts. Intact seed remains from at least 17 plant species (9 families) were found in fecal samples. We concluded that this assemblage of sigmodontine rodents is omnivorous but that they likely play an important role as frugivores and in seed dispersal in tropical montane forests in Peru. El conocimiento de los hábitos alimenticios de roedores pequeños es necesario para comprender cadenas alimenticias, estructura trófica, e interacciones planta-animal en los bosques neotropicales. A pesar de que numerosos estudios han investigado la estructura de comunidades y el comportamiento de forrajeo en roedores, aún existen grandes vacíos en nuestra comprensión de sus gremios tróficos. Nuestro objetivo fue investigar las dietas de siete especies de pequeños (< 100 g) roedores sigmodontinos simpátricos en un bosque montano andino a 3.500] m en Perú. Cualitativamente y cuantitativamente evaluamos la dieta en muestras fecales de roedores capturados entre el 2009 y el 2012. Datos de frecuencia para cuatro categorías de dieta indicaron que las siete especies de roedores consumieron cuatro categorías de dieta: artrópodos (88%), pedazos de hojas y fibras de plantas (61%), semillas intactas (con o sin pulpa de frutos; 50%), y esporas de micorrizas (45%). Omnivoría fue la estrategia utilizada por todas las especies, aunque el análisis con tablas de contingencia reveló diferencias significativas entre y dentro de especies en categorías de dieta. El análisis de agrupación presentó 2 grupos principales: el grupo Thomasomys spp. y Calomys sorellus, que incluye una gran proporción de semillas intactas, y partes de plantas en las muestras fecales y el grupo que incluye los géneros Akodon, Microryzomys y Oligoryzomys, el cual incluyó una proporción mayor de artrópodos en sus muestras fecales, pero con niveles altos de semillas intactas. Semillas intactas de al menos 17 especies de plantas (9 familias) fueron encontradas en las muestras fecales. Concluimos que este ensamble de roedores sigmodontinos es omnívoro y que probablemente las especies juegan un rol importante como frugívoros y en la dispersión de semillas en los bosques montanos tropicales en el Perú.


Antioxidant and pro-oxidant actions of flavonoids: effects on DNA damage induced by nitric oxide, peroxynitrite and nitroxyl anion.
Antioxidant and pro-oxidant activities of flavonoids have been reported. We have studied the effects of 18 flavonoids and related phenolic compounds on DNA damage induced by nitric oxide (NO), peroxynitrite, and nitroxyl anion (NO-). Similarly to our previous findings with catecholamines and catechol-estrogens, DNA single-strand breakage was induced synergistically when pBR322 plasmid was incubated in the presence of an NO-releasing compound (diethylamine NONOate) and a flavonoid having an ortho-trihydroxyl group in either the B ring (e.g., epigallocatechin gallate) or the A ring (e.g., quercetagetin). Either NO or any of the above flavonoids alone did not induce strand breakage significantly. However, most of the tested flavonoids inhibited the peroxynitrite-mediated formation of 8-nitroguanine in calf-thymus DNA, measured by a new HPLC-electrochemical detection method, as well as the peroxynitrite-induced strand breakage. NO- generated from Angeli's salt caused DNA strand breakage, which was also inhibited by flavonoids but at only high concentrations. On the basis of these findings, we propose that NO- and/or peroxynitrite could be responsible for DNA strand breakage induced by NO and a flavonoid having an ortho-trihydroxyl group. Our results indicate that flavonoids have antioxidant properties, but some act as pro-oxidants in the presence of NO.


Drought impact on cropland use monitored with AVIRIS imagery in Central Valley, California.
During 2012-2016 California experienced the longest and most severe drought in the last centuries. This water scarcity led to an increase in non-cultivated croplands during this period. The objective of this study was to quantify agricultural trends in the Central Valley (California) at peak growth from 2013 to 2016 during the drought and in 2017-2018 post-drought. For this purpose, we analysed yearly official harvested area reported at county level for the main crops and compared them to visible-shortwave infrared (VSWIR) spectra acquired by the Airborne Visible/Infrared Imaging-Spectrometer (AVIRIS-classic) over 2334 km2 of the Central Valley each year. Multiple Endmember Spectral Mixture Analysis (MESMA) was applied to AVIRIS data to estimate green vegetation (GV), non-photosynthetic vegetation (NPV) and soil fractions in crop fields each year. MESMA and crop reports (R2 = 0.9) showed that soil (i.e.; non-cultivated areas) increased during the summers of the drought; with the smallest GV area in 2015, the second year classified with exceptional drought in this period. According to MESMA, 34 % of the cropland was covered by GV in 2015, and 69.5·104 ha according to the crop reports. MESMA also registered the highest value of soil area in 2015 (48 %). The year with most cultivated area was 2017, the wettest year in the studied period, with 54 % of the croplands covered by GV and 75.2·104 ha. This study verified that the non-cultivated areas increased in the Central Valley during the exceptional drought period and validated the use of AVIRIS imagery to monitor broad-scale cropland use changes in future climatic extreme events.


The effect of pharmacotherapy on personality disorders in panic disorder: a one year naturalistic study.
In this prospective study, Personality Disorders (PersD) were evaluated in patients with Panic Disorder (PD), before and after one year of pharmacotherapy to verify whether personality characteristics changed after treatment. Sixty PD patients and 60 sex and age-matched normal controls participated in the study. All subjects were evaluated with the SCID-IV, the Structured Interview for DSM-IV Personality Disorders (SIDP), the SCL-90, the Ham-A and the Ham-D. Patients were treated with paroxetine or citalopram and were evaluated monthly for one year to assess the remission of symptoms. The SIDP was re-administered to the patients at the end of the study. Before treatment, PD patients showed a higher prevalence (60%) of PersD than normal subjects (8%). After treatment, PersD rate decreased (43%) due to the reduction of the rate of paranoid, avoidant and dependent PersD. When the effect of the treatment on personality traits was evaluated, we found that avoidant traits decreased only in remitted patients, paranoid traits decreased both in remitted and in non-remitted patients, and dependent traits decreased only in patients with major depression comorbidity. The small sample size and the short length of the follow-up period of our study suggest caution in the generalization of our results. In our PD patients, an improvement of symptoms was associated with a reduction of paranoid, avoidant and dependent traits, with a normalization of paranoid traits and a persistence of avoidant and dependent characteristics. Therefore, our data suggest that in PD patients not only paranoid traits but also avoidant and dependent traits show, at least in part, a state phenomenon.


Laparoscopic fenestration of posttransplant lymphoceles.
A lymphocele is a common finding after renal transplantation and occurs in up to 20% of patients. The majority of patients are asymptomatic. However, once a lymphocele has become symptomatic (e.g., through transplant dysfunction) this condition has to be treated. We report our 9-year experience with laparoscopic lymphocele fenestration and discuss the current management options for posttransplant lymphoceles. Since 1993, 19 patients (11 males and 8 females; median age 56 years, range 22-68 years) of a total of 31 patients with a symptomatic posttransplant lymphocele have undergone laparoscopic fenestration of their lymphocele at a median of 66 days (range, 19-111 days) following successful renal transplantation in our department. As a first-line treatment, a percutaneous pigtail drainage catheter was inserted in all patients. In case of failure in resolving the fluid collection, the next step included sclerotherapy by instillation of tetracycline or ethanol into the lymphocele cavity in some cases. In patients with a persistent lymphocele, a laparoscopic lymphocele fenestration via a transabdominal approach was undertaken to achieve adequate drainage. Primary laparoscopic lymphocele fenestration was successful in all except two patients, who required a conversion. The median operating time was 36 min (range, 20-70 min). Following the procedure, renal transplant function remained stable or returned to individually normal levels in all patients. Median duration of hospital stay was 4 days (range, 1-13 days). At median follow-up of 27 months, all patients were alive with a functioning transplant. Laparoscopic lymphocele fenestration is reserved for patients in whom temporary drainage with or without sclerotherapy failed to resolve the fluid collection. In these cases the laparoscopic approach offers obvious technical and clinical advantages compared to open operative techniques.


Random variation in the masseteric silent period after chin taps.
Although the silent period duration has often been evaluated as a potential indicator of stomatognathic system dysfunction, there is still some uncertainty as to its normal biologic variation. This study investigated the subject variation in the silent period in a group of 22 young and healthy subjects under standardized conditions. Electromyographic recordings were obtained from the masseter muscle at 40% clenching after chin taps. Four different patterns of the silent period were recorded: one simple and three combined. Although the latencies of the early and late phases of depression were generally consistent, the results for duration were more variable and depended on the pattern of the silent period.


Association of CYP19A1 and CYP1A2 genetic polymorphisms with type 2 diabetes mellitus risk in the Chinese Han population.
Type 2 diabetes mellitus (T2DM), one of the global health issues, is a group of metabolic diseases and is affected by several genetic loci in the clinical phenotype. This study intended to ascertain associations between CYP19A1 and CYP1A2 gene polymorphisms with the T2DM risk in Chinese Han. Seven single nucleotide polymorphisms (SNPs) in total including five of CYP19A1 (rs4646, rs6493487, rs1062033, rs17601876 and rs3751599) and two of CYP1A2 (rs762551 and rs2470890) from 512 T2DM patients and 515 non-diabetic controls were genotyped in the platform of Agena MassARRAY. SPSS 18.0 was utilized for analyzing genotyping results. Logistic regression models were conducted for the risk assessment by the odds ratios (ORs) and 95% confidence intervals (CIs). The results suggested a significant association between genotype GC of rs1062033 with a decreased T2DM risk (OR = 0.73, 95% CI = 0.55-0.96, P = 0.025) under the co-dominant (heterozygous) model. The results of stratification analysis with age and gender adjustment revealed that the effects of all selected SNPs in CYP19A1 and CYP1A2 on the T2DM susceptibility were dependent on age, body mass index (BMI) and disease progression (P < 0.05). The haplotype analysis was further conducted and the results indicated that Crs1062033Grs17601876Ars3751599 in CYP19A1 played a protective role (OR = 0.48, 95% CI = 0.25-0.91, P = 0.026) in T2DM patients with diabetic retinopathy. This population-based case-control study suggested that CYP19A1 and CYP1A2 variations might affect the susceptibility of T2DM. The findings provide a theoretical basis for searching the clinical therapeutic markers and attractive drug targets of T2DM.


Reaction pathway and free energy profile determined for specific recognition of oligosaccharide moiety of carboxypeptidase Y.
The interaction of mannose specific lectin (from Lens culinaris, LcL) with the carbohydrate moiety of carboxypeptidase Y (CaY) was studied using both atomic force microscope (AFM) and quartz crystal microbalance with dissipation monitoring (QCM-D). The AFM enables to determine the positions of energy barriers present in the energy landscape of the single complex undergoing dissociation. The QCM-D measurements allow the estimation of the quantitative parameters characterizing the kinetics of the studied molecular interaction (namely the association and dissociation rate constants and the association constant). The use of both methods not only delivers the complementary characterization of kinetic and thermodynamic parameters but also permits to investigate the mechanism of the binding and unbinding of the molecules. The results for LcL were compared with those obtained for concanavalin A i.e. lectin, which interacts with the carbohydrate moiety on a similar way.


Validation of the Acoustic Voice Quality Index Version 03.01 and Acoustic Breathiness Index in German.
The aim of this study was to validate the acoustic voice quality index (AVQI) version 03.01 and the acoustic breathiness index (ABI) in the German language. Concatenated voice samples of continuous speech (cs) and sustained vowel (sv) [a:] from 175 subjects with dysphonia and 43 vocally healthy subjects were perceptually judged for overall voice quality and breathiness severity. First, to reach a higher level of ecological validity, the proportions of cs and sv were equalized regarding the time length. Second, concurrent validity and diagnostic accuracy were statistically verified using the Spearman rank-order correlation coefficient (rs) and several estimates of the receiver operating characteristics, likelihood ratio, and Youden index. A moderate reliability of overall voice quality and breathiness severity from three experts were found. It was found that 27 syllables as standardization of the cs part, which represents 3 seconds of voiced cs, allows the equalization of both speech tasks. A strong correlation was revealed between AVQI and overall voice quality (rs = 0.86, P < 0.01), and ABI and perceived breathiness severity (rs = 0.85, P < 0.01). Additionally, the best diagnostic outcome for AVQI and ABI was identified at a threshold of 1.85 (sensitivity of 72 % and specificity of 90 %) and 3.42 (sensitivity of 72 % and specificity of 95 %), respectively. AVQI and ABI showed in the German language valid and robust results to quantify abnormal voice qualities regarding overall voice quality and breathiness severity.


A 1,10-phenanthroline derivative selectively targeting telomeric G-quadruplex induces cytoprotective autophagy, causing apoptosis of gastric cancer cells.
This study aimed to evaluate the ability of compound 13d to induce autophagy and to promote apoptosis of tumor cells and its interaction mechanism. Using CCK-8 assay, transwell assay, fluorescence resonance energy transfer melting analysis (FRET), transmission electron microscopy, flow cytometry assay, immunofluorescence assay, Western blot analysis, and wound healing assay. The results indicated that compound 13d could induce autophagy and apoptosis of gastric cancer cells. Moreover, the findings of CCK-8 assay, colony formation, migration and invasion assay, and wound healing assay revealed that compound 13d would effectively inhibit cell proliferation, migration, and invasion. Its IC50 value is about 2.4 μM against gastric cancer cells, which is similar to positive drug‑platinum. 13d specific induction of telomere G-quadruplex formation was proved in extracellular FRET melting assay, and indirectly affected telomerase activity. G-quadruplex formation promoted cell apoptosis and autophagy. Upon incorporating the autophagy inhibitors 3-MA and HCQ, the expression of the autophagy marker protein LC3 was then checked, suggesting that the compound 13d influences the autophagy flux. Furthermore, knocking down the autophagy-related gene Atg5 to reduce the level of autophagy enhances the anti-tumor activity and increases apoptotic cells' proportion. Mechanistic experiments have shown that blocking the Akt/m-TOR signal pathway plays a crucial role in autophagy and G-quadruplex induced telomere dysfunction. DNA damage is the leading cause of autophagy. Compound 13d combined with autophagy inhibitor can inhibit tumor cells more effectively. Our findings demonstrate that compound 13d as a telomeric G-quadruplex ligand induces Telomere dysfunction, DNA damage response, autophagy, and apoptosis in gastric cancer cells by blocking the Akt/m-TOR signaling pathway.


Phenotypically complex living materials containing engineered cyanobacteria.
The field of engineered living materials lies at the intersection of materials science and synthetic biology with the aim of developing materials that can sense and respond to the environment. In this study, we use 3D printing to fabricate a cyanobacterial biocomposite material capable of producing multiple functional outputs in response to an external chemical stimulus and demonstrate the advantages of utilizing additive manufacturing techniques in controlling the shape of the fabricated photosynthetic material. As an initial proof-of-concept, a synthetic riboswitch is used to regulate the expression of a yellow fluorescent protein reporter in Synechococcus elongatus PCC 7942 within a hydrogel matrix. Subsequently, a strain of S. elongatus is engineered to produce an oxidative laccase enzyme; when printed within a hydrogel matrix the responsive biomaterial can decolorize a common textile dye pollutant, indigo carmine, potentially serving as a tool in environmental bioremediation. Finally, cells are engineered for inducible cell death to eliminate their presence once their activity is no longer required, which is an important function for biocontainment and minimizing environmental impact. By integrating genetically engineered stimuli-responsive cyanobacteria in volumetric 3D-printed designs, we demonstrate programmable photosynthetic biocomposite materials capable of producing functional outputs including, but not limited to, bioremediation.


Left ventricular pacing site and timing optimization during biventricular pacing using a multielectrode patch in pigs.
Biventricular pacing is important therapy for congestive heart failure, reversing left ventricular dysfunction in dilated cardiomyopathy. Although left ventricular lead location and right ventricular-left ventricular delay are believed to be critical in biventricular pacing, there is no established technique for optimizing pacing site and timing. After median sternotomy in 8 anesthetized pigs, an ultrasonic flow probe was placed on the ascending aorta to measure cardiac output, and pressure catheters were inserted into both ventricles. Temporary bipolar epicardial pacing leads were attached to the right atrium and anterior right ventricle. A patch with 5 bipolar electrodes was placed behind the left ventricle. A temporary bipolar lead was also placed on the left ventricular apex. Complete heart block was established by ethanol ablation. Right ventricular pressure overload was induced by snaring the pulmonary artery until right ventricular systolic pressure doubled. Dual-chamber mode biventricular pacing was instituted at 9 right ventricular-left ventricular delays, +80 ms to -80 ms in 20 ms increments, and 6 left ventricular sites. Data from the 54 combinations of these variables were acquired in a randomized fashion. Mixed model technology was used for statistical analysis. Qualitatively, two unique site/timing pairs were optimal. Statistically, pacing the obtuse margin at a right ventricular-left ventricular delay of +60 ms (mean cardiac output = 1.80 L/min) and the inferolateral wall at a right ventricular-left ventricular delay of -20 ms (mean cardiac output = 1.79 L/min) was superior to all other site/timing combinations (mean cardiac output = 1.71 L/min; P = .006). Left ventricular pacing site and right ventricular-left ventricular delay can be optimized with a multielectrode patch and randomized data collection. This technique can be used further in clinical studies.


Mitochondrial DNA variation of the common hippopotamus: evidence for a recent population expansion.
Mitochondrial DNA control region sequence variation was obtained and the population history of the common hippopotamus was inferred from 109 individuals from 13 localities covering six populations in sub-Saharan Africa. In all, 100 haplotypes were defined, of which 98 were locality specific. A relatively low overall nucleotide diversity was observed (pi = 1.9%), as compared to other large mammals so far studied from the same region. Within populations, nucleotide diversity varied from 1.52% in Zambia to 1.92% in Queen Elizabeth and Masai Mara. Overall, low but significant genetic differentiation was observed in the total data set (F(ST) = 0.138; P = 0.001), and at the population level, patterns of differentiation support previously suggested hippopotamus subspecies designations (F(CT) = 0.103; P = 0.015). Evidence that the common hippopotamus recently expanded were revealed by: (i) lack of clear geographical structure among haplotypes, (ii) mismatch distributions of pairwise differences (r = 0.0053; P = 0.012) and site-frequency spectra, (iii) Fu's neutrality statistics (F(S) = -155.409; P < 0.00001) and (iv) Fu and Li's statistical tests (D* = -3.191; P < 0.01, F* = -2.668; P = 0.01). Mismatch distributions, site-frequency spectra and neutrality statistics performed at subspecies level also supported expansion of Hippopotamus amphibius across Africa. We interpret observed common hippopotamus population history in terms of Pleistocene drainage overflow and suggest recognising the three subspecies that were sampled in this study as separate management units in future conservation planning.


Ceramide: a common pathway for atherosclerosis?
Plasma sphingomyelin concentration is correlated with the development of atherosclerosis. It has been found to exist in significantly higher concentrations in aortic plaque. This appears to have clinical relevance as well as it has been shown to be an independent predictor of coronary artery disease. Ceramide, the backbone of sphingolipids, is the key component which affects atherosclerotic changes through its important second-messenger role. This paper sheds light on some of the current literature supporting the significance of ceramide with respect to its interactions with lipids, inflammatory cytokines, homocysteine and matrix metalloproteinases. Furthermore, the potential therapeutic implications of modulating ceramide concentrations are also discussed.


Antifungal agents as tools in experimental mycology.
Both natural and synthetic substances are conveniently used for studying metabolism, genetic aspects, morphogenesis of cell structures, life cycle and differentiation of fungi.


Intra-articular repair of an isolated partial articular-surface tear of the subscapularis tendon.
Partial-thickness tear of the subscapularis tendon in the articular surface is common. Intra-articular repair of a partial articular-surface tear of the subscapularis tendon will provide a successful outcome. Case series; Level of evidence, 4. A total of 29 shoulders with an isolated partial articular-surface tear of the subscapularis tendon without another rotator cuff lesion were treated with arthroscopic intra-articular repair using suture anchors. Biceps tenodesis was performed in 16 patients. Outcomes were prospectively evaluated at a mean of 27 months (range, 19-41 months) using 3 objective (University of California at Los Angeles, American Shoulder and Elbow Surgeons Shoulder Index, Simple Shoulder Test) and 2 subjective (pain and function visual analog scales) measurements. There were 21 men and 8 women, with a mean age of 54 years (range, 41-65 years). Tear widths were small (<1 cm) in 16 shoulders and large (>1 cm) in 13 shoulders. Twenty-six shoulders had articular cartilage erosion on the adjacent humeral head. Lesions of the biceps tendon were noted in 25 patients (partial tear in 15 shoulders; subluxation in 13 shoulders). Shoulder pain scores improved after surgery (5.0 +/- 2.7 to 0.3 +/- 0.7, P < .05). According to American Shoulder and Elbow Surgeons Shoulder Index scores, 18 were excellent; 10, good; and 1, fair. Internal rotation strength deficit improved from 32% to 4%. Twenty-six patients returned to more than 90% of previous activity. There were no surgical complications; tear size and biceps tenodesis did not affect outcome (P > .05). Arthroscopic intra-articular repair of a partial articular-surface tear of the subscapularis tendon is an effective procedure that spares the intact tendon attachment in the bursal surface. Short-term outcomes were reliable by both objective and subjective measurements.


Intrathecal midazolam reduces isoflurane MAC and increases the apnoeic threshold in rats.
The purpose of this study was to examine the anaesthetic requirement of intrathecal midazolam in a dose-response fashion in isoflurane-anaesthetized, tracheostomized rats, and to evaluate the apnoeic threshold after each intrathecal midazolam dose. Intrathecal midazolam, 5, 10, 20, and 30 micrograms, was administered to 25 anaesthetized tracheotomized rats. Isoflurane MAC was determined by the tail-clamp method. The effect of intrathecal midazolam on the apnoeic threshold was evaluated, and light and electron microscopy studies were performed on cervical, thoracic and lumbar sections of the spinal cord to investigate possible midazolam-induced neurotoxic effects. Intrathecal midazolam 5, 10, 20 and 30 micrograms decreased isoflurane MAC by 16%, 31%, 42%, and 53% respectively (P < 0.05). The apnoeic threshold was increased by midazolam 5 micrograms (from a PaCO2 of 4.25 +/- 0.55 to 5.28 +/- 0.76 kPa, P < 0.05) when compared with baseline values, but not further by additional doses. Light and electron microscopy studies on sections taken from the spinal cord of four animals did not show any morphological changes suggestive of midazolam-induced neurotoxicity when compared with similar preparations obtained from controls. These data suggest that intrathecal midazolam possesses dose-dependent antinociceptive properties which, associated with the ceiling effect of the apnoeic threshold obtained at the lowest midazolam dose and the lack of neurotoxic effects, may potentiate inhalational anaesthesia without producing marked respiratory depression.


Complete response in severe thrombotic microangiopathy post bone marrow transplantation (BMT-TM) after multiple plasmaphereses.
A 44-year-old male with Ph+ chronic myeloid leukaemia (CML) underwent histoidentical allogeneic bone marrow transplantation 18 months after initial diagnosis. He received pretransplant conditioning with busulphan and cyclophosphamide (Bucy). GVHD prophylaxis consisted of methotrexate, cyclosporine (CsA) and methylprednisolone. On day +50, he developed a microangiopathic haemolytic anaemia with indirect bilirubinaemia, 10% fragmented red cells (FC) and an elevated LDH (1213 U/l: normal range 100-185 U/l). Clinical symptoms consisted of edema and hypertension. The patient was not febrile and had no neurological changes. A clinical diagnosis of severe (grade 4) multifactorial (acute GVHD, CMV infection and cyclosporine) BMT-TM was made. He responded following 19 plasma exchanges with replacement with fresh frozen plasma.


Exploitation of artichoke byproducts to obtain bioactive extracts enriched in inositols and caffeoylquinic acids by Microwave Assisted Extraction.
Byproducts from artichoke represent the majority of the mass collected from the plant and constitute an interesting source of bioactive compounds such as inositols and caffeoylquinic acids. In this work, a microwave assisted extraction (MAE) methodology was developed for the simultaneous extraction of these compounds from artichoke stalks, leaves, receptacles and external bracts. Optimal MAE conditions to maximize the extraction of these bioactives and the antioxidant activity were 97 °C, 3 min, ethanol:water (50:50, v/v). Moreover, a GC-MS methodology was also developed for the simultaneous determination of these compounds in a single run; optimal derivatization conditions were achieved using hexamethyldisilazane and N,O-bis(trimethylsilyl)trifluoroacetamide with 1% trimethylchlorosilane. Artichoke receptacle extracts were the richest in caffeoylquinic acids (28-35 mg g-1 dry sample), followed by the bracts (9-18 mg g-1 dry sample), while those from leaves showed the highest concentrations of inositols (up to 15 mg g-1 dry sample). Receptacle extracts also had the highest antioxidant activity (123 mg TE g-1 dry sample) and the greatest concentration of total phenolic compounds (47 mg GAE g-1 dry sample). Therefore, the developed methodology could be considered as a valuable procedure to obtain and characterize bioactive ingredients with industrial interest from artichoke byproducts, opening new routes of revalorization of artichoke agro-industrial residues.


Molecular mechanisms and genomic basis of tigecycline-resistant Enterobacterales from swine slaughterhouses.
The continuous emergence of tigecycline-resistant bacteria is undermining the effectiveness of clinical tigecycline. Environmental tigecycline-resistant bacteria have the potential to infect humans through human-environment interactions. Furthermore, the mechanisms of tigecycline resistance in Enterobacterales are complicated. In this study, we aimed to investigate the additional pathways of tigecycline resistance in environmental Enterobacterales besides tet(X) and tmexCD-toprJ. During the years 2019-2020, tigecycline-resistant Enterobacterales (n = 45) negative for tet(X) and tmexCD-toprJ were recovered from 328 different samples from two slaughterhouses. Five distinct bacteria species were identified, of which Klebsiella pneumoniae (n = 37) was the most common, with K. pneumoniae ST45 and ST35 being the predominant clones. Tigecycline resistance determinants analysis showed that tet(A) mutations and ramR inactivation were the most prevalent mechanisms for tigecycline resistance in the 45 strains. Two known tet(A) variants (type 1 and tet(A)-v) and one novel tet(A) variant (type 3) were identified. Cloning experiments confirmed that the novel type 3 tet(A) could enhance the 4-fold MIC for tigecycline. Inactivation of ramR was induced by either point mutations or indels of sequences, which could result in the overexpression of AcrAB pump genes leading to tigecycline resistance. In addition, all isolates were resistant to a wide range of antimicrobials and carried various resistance genes. These findings enriched the epidemiological and genomic characterizations of tigecycline-resistant Enterobacterales from slaughterhouses and contributed to a better understanding of the complex mechanisms of tigecycline resistance in environmental bacteria.


Effects of combined dexamethasone and tranexamic acid in lower limb total arthroplasty: a systematic review and meta-analysis of randomized clinical trials.
To evaluate the effectiveness of combined Tranexamic acid (TXA) and dexamethasone (DEX) in total hip and knee arthroplasty. PUBMED, EMBASE, MEDLINE and CENTRAL database were systematically searched for randomized studies that utilized TXA and DEX administration of TXA in THA or TKA. A total of three randomized studies enrolling 288 patients were eligible for qualitative and quantitative analysis. DEX + TXA group demonstrated statistical significantly lesser usage of oxycodone (OR: 0.34, p < 0.0001), metoclopramide (OR: 0.21, p < 0.00001), lesser incidence of postoperative nausea and vomiting (OR: 0.27, p < 0.0001), better postoperative range of motion (MD: 2.30, p < 0.00001) and shorter length of hospital stay (MD: 0.31, p = 0.03). Comparable results were seen in total blood loss, transfusion rate and postoperative complications. In this meta-analysis, the combination of TXA and DEX has positive impacts on the usage of oxycodone and metoclopramide, postoperative range of motion, postoperative nausea and vomiting and reduces the length of hospital stay.


Validation of the Evidence-Based Practice Competence Questionnaire for Nursing Students: A Cross-Sectional Study in Greece.
(1) Background: evidence-based nursing has been widely adopted by healthcare facilitators, and it is predicated on the connection between research evidence and clinical practice. The knowledge and implementation of evidence-based practice (EBP) depend on a variety of long-established barriers and attitudes. The purpose of this study was to translate and validate the Greek version of the evidence-based practice competence questionnaire (EBP-COQ) and test it on a sample of Greek undergraduate nursing students. (2) Methods: a cross-sectional analysis was conducted on data obtained between November 2018 and January 2019. A convenience sample of 320 Greek undergraduate nursing students participated in a survey to examine the psychometric properties of the tool. The reliability and validity of the tool was examined. Cronbach's coefficient alpha was used to determine the scale's internal consistency reliability. (3) Results: the EBP-COQ was translated and validated. The estimated Cronbach's alpha was higher than 0.70 for all scales. Of the participants, 22.5% were men and 77.5% were women, while 31% of them were in their final year of nursing education. A total of 61% of the students stated that they had not participated in an EBP seminar in the past. High Spearman's correlation coefficients were found for "Knowledge in EBP" with "Personal attitude towards EBP" (rs = 0.329, p < 0.001). (4) Conclusions: the Greek version of the EBP-COQ is a valid instrument that can be used in the Greek population. It provides information about attitude, knowledge and skills in the EBP approach.


Influence of paternal immunity on idiotype expression of offspring.
The immune response of the rat to group A streptococcal carbohydrate (SACHO) and an associated idiotype, Id-1, was used to examine the effect of paternal immunity on Id-1 and SACHO-specific antibody expression by the offspring. First litters, conceived before immunization of the father, had significantly higher Id-1 levels than litters conceived by the same parental pairs after hyperimmunization of the father (P greater than 0.01). Total anti-SACHO levels were not affected. The effect appeared to be independent of the level of Id-1 expressed by the father or grandfather. No significant difference in Id-1 production was found between offspring of actively immune, neonatally Id-1 suppressed fathers and fathers expressing high levels of Id-1. We suggest that the paternal immunoregulatory influence acts via the maternal immune system to modify the idiotype repertoire expressed in the immune response of the offspring, and is not the result of genetic transmission of a trait acquired by the father. Some possible mechanisms of transmission are discussed.


Phase II study of docetaxel (taxotere) in patients with previously untreated extensive small cell lung cancer.
The objective of this multicenter phase II study was to evaluate the activity of docetaxel in previously untreated small cell lung cancer. Fourteen patients were treated at a dose of 75 mg/m2 intravenously every three weeks. Of the 12 patients evaluable for response, one had a partial response for a duration of 12 weeks for a response rate of 8.3%. Toxicity was mild. We conclude that docetaxel has, at the dose given in this study, little activity in previously untreated small cell lung cancer.


Monitoring platelet dependent thrombin generation in mice.
Calibrated automated thrombin generation assay was adapted to measure thrombin generation in platelet rich plasma from mice. Vena cava phlebotomy appeared the best technique for blood sampling. The concentration-effect curves of tissue factor and platelet count have been determined. Corn trypsin inhibitor 2μM inhibits contact activation effectively. Recombinant human thrombomodulin does not inhibit thrombin generation in mouse plasma but activated protein C (20nM) does. Thrombin generation was dose dependently diminished by low molecular weight heparin and increased by high concentrations of exogenous factor VIII i.e. the assay can detect both hypo- and hypercoagulability.


Resin retention by immersion-etched alloy.
An immersion technique for etching a nonnoble alloy was described. Shear strength measurements were made to compare the bonding of composite luting cement to immersion-etched alloy and to alloy etched by the electrolytic process. The study showed that statistically significant differences in the retention of cement could not be attributed to the method of etching.


Relation between myocardial edema and myocardial mass during the acute and convalescent phase of myocarditis--a CMR study.
Myocardial edema is a substantial feature of the inflammatory response in human myocarditis. The relation between myocardial edema and myocardial mass in the course of healing myocarditis has not been systematically investigated. We hypothesised that the resolution of myocardial edema as visualised by T2-weighted cardiovascular magnetic resonance (CMR) is associated with a decrease of myocardial mass in steady state free precession (SSFP)-cine imaging. 21 patients with acute myocarditis underwent CMR shortly after onset of symptoms and 1 year later. For visualization of edema, a T2-weighted breath-hold black-blood triple-inversion fast spin echo technique was applied and the ratio of signal intensity of myocardium/skeletal muscle was assessed. Left ventricular (LV) mass, volumes and function were quantified from biplane cine steady state free precession images. 11 healthy volunteers served as a control group for interstudy reproducibility of LV mass. In patients with myocarditis, a significant decrease in LV mass was observed during follow-up compared to the acute phase (156.7 +/- 30.6 g vs. 140.3 +/- 28.3 g, p < 0.0001). The reduction of LV mass paralleled the normalization of initially increased myocardial signal intensity on T2-weighted images (2.4 +/- 0.4 vs. 1.68 +/- 0.3, p < 0.0001). In controls, the interstudy difference of LV mass was lower than in patients (5.1 +/- 2.9 g vs. 16.3 +/- 14.2 g, p = 0.02) resulting in a lower coefficient of variability (2.1 vs 8.9%, p = 0.04). Reversible abnormalities in T2-weighted CMR are paralleled by a transient increase in left ventricular mass during the course of myocarditis. Myocardial edema may be a common pathway explaining these findings.


A possible role for guanosine 3',5'-monophosphate in the stimulus-secretion coupling in exocrine pancreas.
Carbamylcholine, caerulein and cholecystokinin octapeptide rapidly increased the cyclic GMP concentration and amylase secretion in isolated guinea pig pancreatic slices. The cyclic GMP concentration was increased eight-fold over the basal concentration in 30 s, with concomitant increase in the rate of amylase secretion. The tissue concentration of cyclic GMP then rapidly declined to a plateau value of approx. 16% of the peak level within 10 min and was maintained at that concentration for the duration of the experiment. We have shown earlier (Kapoor, CL. and Krishna, G. (1977) Science 196, 1003--1005) that the decrease of tissue cyclic GMP was due mainly to the secretion of cyclic GMP into the medium. The cyclic AMP concentration in the tissue was not changed, nor was it secreted into the medium. There was a correlation between the concentration response to various agents for the increase in cyclic GMP concentration and amylase secretion in pancreatic slices. Carbamylcholine increased both the cyclic GMP concentration and amylase secretion; the half-maximal effect was achieved at 1.5 micrometer concentration. Caerulein and cholecystokinin octapeptide were 5000 times more potent than carbamylcholine in increasing cyclic GMP concentration and amylase secretion; the half-maximal effect was achieved at 0.3 nM concentration. Atropine, which completely inhibited the increase in cyclic GMP and amylase secretion induced by carbamylcholine, did not block the effects of caerulein or cholecystokinin octapeptide. These results suggest that various secretagogues induced amylase secretion by increasing the cyclic GMP concentration, but the mechanism by which cyclic GMP caused amylase secretion remains to be elucidated.


Estradiol protects clomiphene citrate-induced apoptosis in ovarian follicular cells and ovulated cumulus-oocyte complexes.
To determine whether clomiphene citrate (CC) reduces E(2) level in the ovary and circulation and induces apoptosis in ovarian follicular cells and ovulated cumulus-oocyte complexes (COCs). If yes, to determine whether E(2) coadministration could protect against these adverse effects of CC. A controlled prospective study. Laboratory research setting. Ninety sexually immature female rats that were 24-25 days of age. The immature female rats were injected with a single dose of 10 IU of pregnant mare serum gonadotropin. After 48 hours, 10 IU of hCG along with 10 mg of CC per kilogram of body weight, with or without 2.0 mg of E2 per kilogram of body weight were coadministered. After 16 hrs, the rats were killed; COCs were collected from oviduct and ovaries were isolated. Number of superovulated COCs, oocyte morphology, E2 level in ovary and serum, histology of ovary, DNA fragmentation, and bax protein expression in ovary and COCs. The number of COCs and E2 level in ovary and serum were reduced, whereas membrane blebbing in oocytes, bax protein expression, and DNA fragmentation in ovarian follicular cells and ovulated COCs were induced after CC treatment. These adverse effects of CC were protected against if animals were coadministered with E2. Clomiphene citrate-induced apoptosis in ovarian follicular cells (probably granulosa cells), thereby reducing E2 level in ovary and circulation that might have resulted in poor development and maturation of oocytes leading to reduced ovulation.


Impact of heating and drying temperatures on the properties of konjac glucomannan/curdlan blend films.
The impact of preparation conditions including heating temperature (from 60 °C to 90 °C) and drying temperatures (from 25 °C to 90 °C) on the properties of pure curdlan film and konjac glucomannan (KGM) and curdlan blend films were analyzed. Microstructure analysis indicated the KGM addition could significantly improve the relatively poor film-forming property of curdlan. FTIR and X-ray analysis showed that at high heating temperature 90 °C, molecular interaction might be enhanced in the films due to the stretched structure of curdlan and dissociation of curdlan bundles or triple-helix structure. This was supported by the changes in the mechanical property, surface hydrophobicity, moisture barrier, and moisture tolerance property. The impacts of drying temperature were some different for the curdlan film and KGM/curdlan blend film, and were explained from the molecular hydrophilicity-hydrophobicity, compactness of the films, curdlan conformation, and molecular interaction. This work guided biodegradable film production especially with curdlan added.


The association between MUC5AC and MUC5B genes expression and remodeling progression in severe neutrophilic asthma: A direct relationship.
MUC5 dysregulation is a hallmark of severe neutrophilic asthmatic patients. This study investigates the expression of MUC5AC and MUC5B at mRNA levels on asthma severity and airway wall thickness in severe neutrophilic asthmatic patients. In this case-control clinical trial, twenty-five severe neutrophilic asthmatic patients and ten control subjects were enrolled. Subjects underwent ACT, pulmonary functions tests, and fractional exhaled nitric oxide (FENO). Also, induced sputum has been obtained to assess the expression of MUC5AC and MUC5B by the real-time PCR. In addition, the thickness of the airway wall was assessed by high-resolution computed tomography (HRCT), and bioinformatic analysis was implemented to approve the selection of the appropriate genes and for further investigations. A significant difference was observed between the asthmatic and control in MUC5AC and MUC5B mRNA expression. Meanwhile, the expression of MUC5AC increased remarkably by asthma severity; also, it is associated with airway wall thickness (WT) (both P-value <0.05). The expression of MUC5B in asthmatic patients was lower than in control. There is no significant correlation between MUC5B mRNA level and WT and asthma severity. Notably, MUC5AC transcription level was correlated to sputum neutrophil percentage, while MUC5B transcription level had a positive correlation with sputum macrophages and a negative one with sputum neutrophils. In severe neutrophilic asthma, airway wall thickness increases with MUC5AC mRNA overexpression, which is probably related to asthma severity and the formation of mucus plugs. However, the expression of MUC5B was decreased, resulting in poor mucociliary clearance in the airways. IR.IAU.MSHD.REC.1400.124.


[Differential therapy of prostate cancer].
Prostate cancer has become the most common malignancy in males worldwide. Standard therapy in local confined prostate cancer with curative intent is a radical ablation of the gland. Brachytherapy seems to be an alternative treatment but long-term results are not yet available. In cases of advanced disease androgen deprivation is applied to eliminate testosterone which is the natural stimulator of tumor growth. The application of chemotherapy is limited to androgen-independent disease without curative intention. Standard chemotherapy is Docetaxel. Both early detection and aftercare are based on measurement of prostate-specific antigen.


Sexual size dimorphism and male combat in snakes.
This paper reviews published literature on snakes to test the hypothesis that large male size, relative to female size, evolves because of the advantage it confers in male combat. Analysis of the data reveals a high correlation between the occurrence of male combat, and sexual dimorphism in which the male is the larger sex. This correlation holds (i) within the total sample of snake species (n=224), (ii) within the family Colubridae (n=134), and (iii) in a comparison between the eight families of snakes for which data are available. These results strongly support the hypothesis that large male size is an adaptation to intrasexual competition. The analysis also shows that females are larger than males in about 66% of snake species, that male combat is known in only about 15% of species, and that both sexual size dimorphism and the incidence of male combat tend to be distributed along taxonomic lines.


Pre- and postsynaptic effects of taurine and GABA in the cockroach central nervous system.
Taurine resembles GABA in its synaptic effects in the cockroach cercal nerve giant fiber synapse where it exerts a depressant action upon synaptic transmission. Both taurine and GABA produce an increased conductance of pre- and postsynaptic membranes through changes in the permeability of chloride ions.


Relating the physical properties of aqueous solutions of ionic liquids with their chemical structures.
The physical properties of an aqueous solution of a macromolecule primarily depend on its chemical structure and the mesoscopic aggregates formed by many of such molecules. Ionic liquids (ILs) are the macromolecules that have caught significant research interests for their enormous industrial and biomedical applications. In the present paper, the physical properties, such as density, viscosity, ionic conductivity of aqueous solutions of various ILs, have been investigated. These properties are found to systematically depend on the shape and size of the anion and the cation along with the solution concentration. The ionic conductivity and viscosity behavior of the solutions do not strictly follow the Walden rule that relates the conductivity to the viscosity of the solution. However, the modified Walden rule could explain the behavior. A simple calculation based on the geometry of a given molecule could shed the light on the observed results.


Cross-sensitive rare-earth metal sensors based on bidentate neutral organophosphorus compounds and chlorinated cobalt dicarbollide.
A variety of new chemical sensors (ion selective electrodes) for determination of rare-earth (RE) and trivalent metal cations such as yttrium(III), lanthanum(III), praseodymium(III), neodymium(III) and europium(III) that are commonly present in aqueous radiological samples, e.g. in high-level liquid waste (HLW) and solutions from reprocessing spent nuclear fuel, have been developed and studied. The sensors are based on bidentate neutral organophosphorus compounds, such as methylene bridged diphosphine dioxides and carbamoylmethylphosphine oxides, which are efficient extractants, especially when used in conjunction with chlorinated cobalt dicarbollide, for recovery and concentration of the RE and actinide elements from acidic HLW derived from the nuclear fuel cycle. The sensors exhibit remarkable sensitivity to RE cations and indicate promise for HLW analysis.


Nonlinear adaptive control of tuberculosis with consideration of the risk of endogenous reactivation and exogenous reinfection.
Tuberculosis is one of deadly diseases in many countries that attacks to the human body and causes damage to the lung, causing bloody coughing and if left untreated, it will kill half of the affected people. Tuberculosis bacteria can stay latent and reactivate after passing appropriate conditions. For this reason, control of this disease and treatment of infected people has a significant importance, and observing health issues can prevent the spread of it. In this paper, a nonlinear adaptive control method is proposed for the first time in order to control and treat tuberculosis outbreak subjected to the modeling uncertainty. To design a control system being robust against uncertainties, an adaptation law is defined to update values of estimated parameters and ensures the whole system stability. The treatment achievement and stability of the closed-loop system is proved by the Lyapunov theorem and confirmed by some simulations. The proposed strategy has the capability to control the tuberculosis outbreak by reducing the numbers of active infectious and persistent latent individuals based on their desired values in the society.


The psbA gene family responds differentially to light and UVB stress in Gloeobacter violaceus PCC 7421, a deeply divergent cyanobacterium.
Gloeobacter violaceus PCC 7421 is a slow-growing cyanobacterium which lacks thylakoid membranes, but whose five-membered psbA gene family encodes three isoform variants of the PsbA (D1) reaction center protein of Photosystem II. Under standard culture conditions Gloeobacter exhibits photosystem II electron transport, but several clear modifications in the redox potential of key cofactors bound by the PsbA protein are manifested in the flash-fluorescence characteristics. In other cyanobacteria dynamic expression of multiple psbA genes and turnover of PsbA isoforms is critical to counter excitation stress. We found that each of Gloeobacter's five psbA genes is expressed, with transcript abundances spanning 4.5 orders of magnitude. psbAI (glr2322) and psbAII (glr0779), encoding identical PsbA:2 form proteins, are constitutively expressed and dominate the psbA transcript pool under control conditions. psbAIII (gll3144) was strongly induced under photoinhibitory high irradiance stress, thereby contributing to a large increase in the psbA transcript pool that allowed cells to maintain their PsbA protein pools and then recover from irradiance stress, within one cellular generation. In contrast, under comparable photoinhibition provoked by UVB the cells were unable to maintain their psbA transcript and PsbA protein pools, and showed limited subsequent recovery. psbAIV (glr1706) and psbAV (glr2656), encoding two divergent PsbA isoforms, showed consistent trace expression but were never quantitatively significant contributors to the psbA transcript pool.


The pervalence of caecal threadworms (Trichostrongylus tenuis) in red grouse (Lagopus lagopus scoticus).
Ninety percent of wild red grouse examined carried threadworms in their intenstinal caeca. Old birds had 30 times as many worms as young birds. Some infections were as high as 30,000 worms. The occurrence of worms in old grouse conformed to the negative binomial distribution.


Effects of dichloroacetate administration during fatal hemorrhagic shock in immature swine.
During hemorrhagic shock, decreased perfusion and poor tissue oxygenation lead to increased lactate production. Previous animal studies have suggested that sodium dichloroacetate (DCA), an agent that decreases lactate production, can improve hemodynamics and survival when administered after severe hemorrhage. We used an unanesthetized porcine hemorrhagic shock model to assess the effect of DCA on survival time when administered during fatal hemorrhage. Immature female swine weighing 14 to 20 kg were splenectomized and instrumented with chronic indwelling aortic and right atrial catheters one week prior to hemorrhage. On the day of the experiment, the unanesthetized animals' aortic catheter was connected to a roller pump and blood was removed at a rate of 1.0 mL/kg/min until death occurred. Experimental animals (n = 8) received sodium dichloroacetate (25 mg/mL distilled water) 100 mg/kg IV bolus beginning 15 minutes after the start of hemorrhage followed by a 3 mg/kg/min constant IV infusion. Control animals (n = 8) received an equal volume of normal saline. Arterial pressure, heart rate, blood gases, serum lactate, and serum glucose were measured at baseline and every 15 minutes during hemorrhage. There were no significant differences in survival time (controls, 63 +/- 2.8 min; DCA-treated, 60 +/- 3.7 min), lactate levels, or blood pressures between the two groups. These results suggest that DCA does not decrease serum lactate or improve survival time when administered during ongoing severe hemorrhagic shock. Further study should be directed at the effects of DCA as an adjunctive treatment after hemorrhage has been controlled and tissue perfusion restored.


[Rubinstein-Taybi syndrome and juvenile glaucoma].
In a six-year-old girl with Rubinstein-Taybi syndrome the ophthalmological findings were as follows: bushy brows, hypertelorism, epicanthus, an antimongoloid slant to the eyelids and hyperopia with an alternating convergent squint. In the sixth year of life juvenile glaucoma with deep cupping of the disk was found.


Memory encoding and retrieval on the ascending and descending limbs of the blood alcohol concentration curve.
Little is known about acute effects of alcohol on memory encoding and retrieval on different limbs (ascending and descending) of the blood alcohol concentration (BAC) curve. This extensive experiment was designed to examine alcohol's effects on memory encoding and retrieval throughout a protracted drinking episode. In a 9-h session, male participants consumed either alcohol (1 ml/kg) or placebo (n = 32/32) over a period of 90 min and learned various materials in different memory tasks before, during, and after consuming the drinks, while their BAC levels were monitored. A week later, in a similar session, they were tested on learned materials before, during, and after drinking. Mood was assessed throughout both sessions. Alcohol impaired recall of words more than recognition, and cued recall most severely. Perceptual priming and picture recognition were not affected by alcohol. Alcohol impaired encoding in cued recall, recognition of completed word fragments, and free recall regardless of limb, but impaired retrieval in word recognition only during the ascending BAC. Alcohol increased negative mood on the descending limb during the first session, and on the ascending limb during the second session. Under naturalistic drinking conditions, alcohol's effects on memory depend on task, memory process, and limb of the BAC curve. The differential effects of alcohol on retrieval during the ascending and descending limbs demonstrate the importance of examining the differential effects on the two limbs.


The first report of Histophilus somni pneumonia in Nigerian dairy cattle.
Clinical signs of severe bronchopneumonia, including anorexia, coughing, nasal discharge, dyspnoea, diarrhoea, distension of the neck, lethargy, recumbency, lameness preceding collapse, and death were observed among a herd of Holstein-Friesian dairy cattle. The outbreak occurred over a 30-day period, and attack and case-fatality rates were 0.4% and 50%, respectively. At necropsy, extensive consolidation in the cranioventral parts of the lungs was observed. Histologically, a severe acute bronchopneumonia with slight pleuritis was present. Both pathological and bacteriological evaluation of the lungs incriminated Histophilus somni (heavy growth). Supplementary laboratory investigations also isolated Clostridium and Klebsiella species (scanty growth) from the lungs. Histophilosis in cattle was confirmed for the first time in Nigeria.


Characterizing spatiotemporal dynamics of methane emissions from rice paddies in Northeast China from 1990 to 2010.
Rice paddies have been identified as major methane (CH(4)) source induced by human activities. As a major rice production region in Northern China, the rice paddies in the Three-Rivers Plain (TRP) have experienced large changes in spatial distribution over the recent 20 years (from 1990 to 2010). Consequently, accurate estimation and characterization of spatiotemporal patterns of CH₄ emissions from rice paddies has become an pressing issue for assessing the environmental impacts of agroecosystems, and further making GHG mitigation strategies at regional or global levels. Integrating remote sensing mapping with a process-based biogeochemistry model, Denitrification and Decomposition (DNDC), was utilized to quantify the regional CH(4) emissions from the entire rice paddies in study region. Based on site validation and sensitivity tests, geographic information system (GIS) databases with the spatially differentiated input information were constructed to drive DNDC upscaling for its regional simulations. Results showed that (1) The large change in total methane emission that occurred in 2000 and 2010 compared to 1990 is distributed to the explosive growth in amounts of rice planted; (2) the spatial variations in CH₄ fluxes in this study are mainly attributed to the most sensitive factor soil properties, i.e., soil clay fraction and soil organic carbon (SOC) content, and (3) the warming climate could enhance CH₄ emission in the cool paddies. The study concluded that the introduction of remote sensing analysis into the DNDC upscaling has a great capability in timely quantifying the methane emissions from cool paddies with fast land use and cover changes. And also, it confirmed that the northern wetland agroecosystems made great contributions to global greenhouse gas inventory.


A Ceratopteris EXCESS MICROSPOROCYTES1 suppresses reproductive transition in the fern vegetative leaves.
Land plant sexual reproduction involves the transition of cells from somatic to reproductive identity during post-embryonic development. In Arabidopsis, the leucine-rich repeat receptor-like kinase EXCESS MICROSPOROCYTES1 (EXS/EMS1) restricts the number of sporogenous cells during the transition from diploid tissue to haploid spore production by promoting the formation of the tapetum cell layer within the anther. Although all land plants studied contain EMS1 genes, its function is unknown beyond a few angiosperms. In the model fern Ceratopteris (Ceratopteris richardii), we discovered an EMS1 homolog (CrEMS1) that functions to suppress formation of reproductive structures on vegetative leaves of the fern sporophyte, a role not found in angiosperms. Suppression of CrEMS1 by RNAi did not affect sporogenesis on reproductive leaves but did affect antheridium production of the fern gametophyte. Expression patterns of CrEMS1 across developmental stages suggest threshold levels of CrEMS1 control the specification of reproductive organs during both generations of the fern. Additional EMS1 homologs present in the fern genome suggest a dynamic role of EMS1 receptors in the evolution of reproductive development in vascular plants.


A computed tomography study of coronary access and coronary obstruction after redo transcatheter aortic valve implantation.
The aim of this study was to investigate the risk of impaired coronary access and coronary obstruction after redo TAVI. Post-procedure multidetector computed tomography (MDCT) scans of 221 TAVI recipients were analysed. Increased risk of impaired coronary access was defined as a coronary ostium below the TAVI commissures with a valve-to-aorta distance <2 mm at this level. Increased risk was found in 123 (55.6%) cases: the left main was involved in 109 (49.3%), the right coronary in 79 (35.7%), and both were involved in 65 (29.4%) patients. A small sinotubular junction (STJ width OR 0.68, CI: 0.56-0.81, p<0.001; STJ height OR 0.81, CI: 0.69-0.95, p<0.011) and supra-annular devices (OR 19.8, CI: 6.6-58.8, p<0.001) predicted increased risk. Increased risk of coronary obstruction, defined as a coronary ostium below the TAVI commissures with a valve-to-coronary distance <2 mm, was observed in 14.9% of patients; in 17.2% of cases complete sealing of the STJ would occur. Post-TAVI MDCT suggested an increased potential risk of impaired coronary access in more than half of the patients should redo TAVI be required, predicted by a small STJ and supra-annular device design. Furthermore, 10-20% of patients presented an increased risk of coronary obstruction. While this theoretical study is hypothesis-generating, it raises concerns that need to be further investigated and addressed before TAVI is extended to patients with longer life expectancy.


Identification of a novel small-molecule inhibitor targeting TIM-3 for cancer immunotherapy.
PD-1/PD-L1 blockade has achieved substantial clinical results in cancer treatment. However, the expression of other immune checkpoints leads to resistance and hinders the efficacy of PD-1/PD-L1 blockade. T cell immunoglobulin and mucin domain 3 (TIM-3), a non-redundant immune checkpoint, synergizes with PD-1 to mediate T cell dysfunction in tumor microenvironment. Development of small molecules targeting TIM-3 is a promising strategy for cancer immunotherapy. Here, to identify small molecule inhibitors targeting TIM-3, the docking pocket in TIM-3 was analyzed by Molecular Operating Environment (MOE) and the Chemdiv compound database was screened. The small molecule SMI402 could bind to TIM-3 with high affinity and prevent the ligation of PtdSer, HMGB1, and CEACAM1. SMI402 reinvigorated T cell function in vitro. In the MC38-bearing mouse model, SMI402 inhibited tumor growth by increasing CD8+ T and natural killing (NK) cells infiltration at the tumor site, as well as restoring the function of CD8+ T and NK cells. In conclusions, the small molecule SMI402 shows promise as a leading compound which targets TIM-3 for cancer immunotherapy.


Ventilatory management in acute lung injury.
Practical theoretic aspects of the adult respiratory distress syndrome and its application to the patient are presented. Rational utilization of mechanical ventilation and positive end-expiratory pressure in the management of hypoxemia is discussed in detail.


Cytotoxicity studies of human melanoma cells and fibroblasts.
In seven human melanoma cell lines and one human fibroblast strain some correlation of resistance to cell killing was found with two bifunctional alkylating agents (melphalan, chlorambucil) and three monofunctional agents (4(5)-(3,3-dimethyl-l-triazeno)imidazole-5(4)-carboxamide (DTIC), methylmethane sulphonate (MMS) and N-methyl-N1-nitro-N-nitrosoguanidine (MNNG), but little cross-resistance was found between these two groups of agents or with cytosine arabinoside (ara-C). In contrast to previous studies with rodent tumours, potentially synergistic (chloroquine, arginine) or antagonistic (ascorbic acid, leucine) compounds did not affect the toxicity of melphalan in a human melanoma cell line. In two melanoma lines DTIC induced patterns of DNA damage (inhibition of semi-conservative synthesis) and repair (strand breaks and repair synthesis) similar to, but not identical with, those induced by the methylating agent MMNG. These results suggest that a methylating species is derived from DTIC but has a different reactivity toward DNA compared with MNNG.


A retrospective study on clinical findings of 7300 cases (2007-2014) of barren female dromedaries.
The objective of this study was to investigate the clinical findings in barren female dromedaries examined for different complaints. Female camels were examined for repeat breeding with regular heat interval (RB-R, n = 5444), refused mating (RM, n = 1299), repeat breeding with long heat interval (RB-L, n = 489), difficulties or bleeding during mating (DM, n = 53), and for manifestation of male-like behavior (MB, n = 15). The genital tracts of all females were evaluated using transrectal palpation, ultrasonography, and exploration of the vagina. Cervical swabs were obtained for bacteriologic examination. Clinical endometritis, ovarian hydrobursitis, and vaginal adhesions were the main clinical findings in the female camels examined for RB-R, RM, and RB-L, respectively. Parity affected the frequency of occurrence of these findings. The incidences of clinical endometritis, ovarian hydrobursitis, and vaginal adhesions in nullipara and multipara were 28% versus 32.3% (P = 0.004), 37.1% versus 23.7% (P = 0.001), and 5.7% versus 18.3% (P = 0.001), respectively. Vaginal adhesions, persistent hymen, pelvic abscess, and vulvar atresia were the clinical findings in the female camels presented due to bleeding at mating or with a history of an incomplete intromission of the penis. The male-like behavior was associated with an enlargement of the clitoris and narrowing of the vulva and vagina. Trueperella pyogenes, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, Streptococcus zooepidemicus, and β-hemolytic Streptococcus were isolated from females presented for repeat breeding syndrome. In conclusion, clinical endometritis, ovarian hydrobursitis, and vaginal adhesions were the main clinical findings in barren female dromedaries. Parity affected the frequency of the clinical findings.


Reduction of gallstone formation by ascorbic acid in hamsters.
The addition of 0.5% of ascorbic acid to the lithogenic diet of golden hamsters whose body pool was labelled with 26-14C-cholesterol, lowered the formation of gallstones, the cholesterol concentration and half-life in blood plasma and in the liver, and accelerated cholesterol transformation to bile acids.


Wireless on-demand and networking of Puritan Bennett 840 ventilators for direct data capture.
Manual transcription inaccuracies have been reported to be a frequent occurrence in clinical practice, which has been confirmed in my institution. I explored alternative methods of obtaining data directly from the Puritan Bennett ventilator. The aim of this project was to record all of the ventilator settings and monitored data with wireless technology. I evaluated 2 data-capture methods: on-demand data capture into a personal digital assistant, and continuous ventilator networking with a stand-alone computer. I was successful in both the intensive care unit and laboratory environment in transferring ventilator data, for up to several days, and with a data-capture interval as short as 60 seconds.


Perception of contingency and mental retardation.
It is argued that the general learning difficulties exhibited by mentally retarded persons are similar in many respects to the learning difficulties of nonretarded persons who are in a state of learned helplessness (Seligman, 1975) or who are external in locus of control orientation. It is suggested that studies of locus of control and learned helplessness as theoretical constructs both directly concern the perceiving of relationships between behavior and outcomes, and that a systematic investigation of perception of contingency might increase our understanding of some of the learning difficulties of mentally retarded persons. An overview is given of the results of the few studies that have addressed perception of contingency and mental retardation, and suggestions for future research are offered.


Advice on good practice from the Standards Committee.
The role of the General Medical Council has changed over the last few years and this paper shows how the GMC now gives advice on good practice, as well as a warning against bad practice.