Optimized split nitrogen fertilizer increase photosynthesis, grain yield, nitrogen use efficiency and water use efficiency under water-saving irrigation.
This study aims to investigate optimization of the basal-top-dressing nitrogen ratio for improving winter wheat grain yield, nitrogen use efficiency, water use efficiency and physiological parameters under supplemental irrigation. A water-saving irrigation (SI) regime was established and sufficient irrigation (UI) was used as a control condition. The split-nitrogen regimes used were based on a identical total nitrogen application rate of 240 kg ha-1 but were split in four different proportions between sowing and the jointing stage; i.e. 10:0 (N1), 7:3 (N2), 5:5 (N3) and 3:7 (N4). Compared with the N1, N2 and N4 treatments, N3 treatment increased grain yield, nitrogen and water use efficiencies by 5.27-17.75%, 5.68-18.78% and 5.65-31.02%, respectively, in both years. The yield advantage obtained with the optimized split-nitrogen fertilizer application may be attributable to greater flag leaf photosynthetic capacity and grain-filling capacity. Furthermore, the N3 treatment maintained the highest nitrogen and water use efficiencies. Moreover, we observed that water use efficiency of SI compared with UI increased by 9.75% in 2016 and 10.79% in 2017, respectively. It can be concluded that SI along with a 5:5 basal-top-dressing nitrogen ratio should be considered as an optimal fertigation strategy for both high grain yield and efficiency in winter wheat.


Patterns of risperidone prescription: a utilization study in south-west France.
To describe the patterns of prescriptions associated with risperidone in naturalistic clinical practice. We analysed 500 prescription forms randomly selected from the social security insurance database in Aquitaine (south-west France). The prevalence of co-prescription was 42.5% for antidepressants, 46.4% for benzodiazepines, 26.6% for other neuroleptics, 21.8% for mood stabilizers and 19% for anticholinergic drugs. The high prevalence of co-prescribed antidepressants (59.3% Selective Serotonin Reuptake Inhibitors) may be explained by the frequent comorbidity of mood disorders in schizophrenia, and by the fact that risperidone was prescribed in naturalistic conditions in disorders other than schizophrenia. The high level of concomitant drug prescription in patients treated with risperidone illustrates the gap between clinical trials and utilization in naturalistic settings. The association antidepressant-risperidone has been insufficiently studied for efficacy or safety, and has to be explored further from both a pharmacological and clinical point of view.


Immunocytochemistry of the Microtubules of fat-laden cells. Brown fat cells and adrenocortical cells in primary monolayer culture.
Cytoplasmic microtubules of fat-laden cells containing fine lipid droplets, such as brown fat cells and adrenocortical cells, were studied in relation to the metabolism of intracellular lipid. In these cells, the amount and distribution of lipid droplets reflect the state of inherent cellular function. Materials used were primary monolayer culture of fetal rat brown fat cells and that of bovine adrenocortical cells. The method was the immunocytochemistry with anti-tubulin antibody. When brown fat cells were being lipolyzed or the steroidogenesis of adrenocortical cells were being stimulated, the cytoplasmic microtubules in the cells were organized in a radial pattern in response to the behavior of the lipid droplets. It is assumed that the microtubules were in the regulation of cellular function in terms of the metabolism of lipid droplets in these cells. We have devised, in the course of the current study, a double fluorescence technique as an observational method whereby microtubules were observed immunocytochemically and lipid droplets by a secondary fluorescence with phosphine E staining.


Evaluation of susceptibility of human herpesvirus 8 to antiviral drugs by quantitative real-time PCR.
A new in vitro system based on real-time PCR was developed for evaluation of human herpesvirus 8 susceptibility to antiviral agents. Cidofovir had the greatest inhibitory activity against HHV-8 (50% inhibitory concentration [IC(50)], 0.43 microM) followed by ganciclovir (2.61 microM), adefovir (18.00 microM), acyclovir (31.00 microM), and foscarnet (34.15 microM). The potential therapeutic efficacy for HHV-8 (i.e., peak serum drug level/IC(50)) is highest for cidofovir (167) and foscarnet (22).


An Effect of Landmarks on Territory Shape in a Convict Cichlid.
We determine size, shape and location for a territory that is optimal in the sense of minimizing defense costs, when a given proportion of the boundary is landmarked and its primary benefit in terms of fitness is greater ease of detecting intruders across it. Increasing the landmarked proportion of boundary causes the optimal configuration to be smaller and more elongated, and to be located with its center further from the nest, so that the nest is closer to the landmarked boundary. These predictions accord with observations in a recent study of the convict cichlid Amatitlania siquia. Our results thus confirm the consistency of the observed behavior with the hypothesis that A. siquia designs its territory to make intruders easier to spot. Our results also lead us to conjecture that moving the landmark proportionately closer to or further away from the nest would have yielded essentially the same outcome in this study, because the optimal configuration depends only on the angle subtended by the landmark at the nest and hence only on the length of the landmark relative to its distance from the nest, as opposed to its absolute value.


Hyperacetylated chromatin domains mark cell type-specific genes and suggest distinct modes of enhancer function.
Stratification of enhancers by signal strength in ChIP-seq assays has resulted in the establishment of super-enhancers as a widespread and useful tool for identifying cell type-specific, highly expressed genes and associated pathways. We examine a distinct method of stratification that focuses on peak breadth, termed hyperacetylated chromatin domains (HCDs), which classifies broad regions exhibiting histone modifications associated with gene activation. We find that this analysis serves to identify genes that are both more highly expressed and more closely aligned to cell identity than super-enhancer analysis does using multiple data sets. Moreover, genetic manipulations of selected gene loci suggest that some enhancers located within HCDs work at least in part via a distinct mechanism involving the modulation of histone modifications across domains and that this activity can be imported into a heterologous gene locus. In addition, such genetic dissection reveals that the super-enhancer concept can obscure important functions of constituent elements.


Respiratory Tract Infections in Children.
Respiratory tract infections are a major threat, causing morbidity and mortality, especially among children [...].


Homocystinuria and carotid arteriography.
This is a report of a case of homocystinuria where the diagnosis was suggested by the carotid arteriogram.


Obesity in BSB mice is correlated with expression of genes for iron homeostasis and leptin.
We searched for genes whose alleles cause obesity and novel pathways correlated with obesity. BSB mice are a model of complex obesity due to interactions among genes from C57BL/6J (B) and Mus spretus (SPRET) in (B x SPRET) x B backcross mice. Stringent criteria identified 50 genes differentially expressed in epididymal adipose tissue from 7 pairs of lean vs. obese BSB mice. Quantitative reverse transcription-polymerase chain reaction of adipose tissue RNA from 48 BSB mice with a range of obesity was assayed. Leptin was evaluated in inbred (SPRET/Ei) and outbred (SPRET/Pt) BSB mice. Leptin (Lep) and adipsin expressions had the greatest fold differences between obese and lean mice. Four genes involved in iron homeostasis were included in the 50 differentially expressed genes [hemochromatosis (Hfe), diaphorase 1, transferrin receptor (Trfr) 2, and protoporphyrinogen oxidase] and two additional iron-related genes did not quite meet the stringent criteria for differential expression (Trfr and lactotransferrin). Hfe and Trfr mRNA levels and liver iron were negatively correlated with fat mass. Variation in obesity phenotypes explained 49%, 40%, and 37%, respectively, of the variance in Hfe, Lep, and Trfr mRNA levels. Leptin differed by haplotype at the Lep locus in outbred BSB. The quantitative trait locus identified in the outbred cross did not occur in inbred BSB. Our results suggest that iron homeostasis in BSB mice is coordinately regulated in vivo in adipose depots in response to obesity. Lep alleles derived from outbred, but not inbred, SPRET are a positional candidate for the chromosome 6 quantitative trait locus in BSB mice.


Complete Genome Sequence of a New Maize-Associated Cytorhabdovirus.
A new 11,877-nucleotide cytorhabdovirus sequence with 6 open reading frames has been identified in a maize sample. It shares 50 and 51% genome-wide nucleotide sequence identity with northern cereal mosaic cytorhabdovirus and barley yellow striate mosaic cytorhabdovirus, respectively.


Clinical pharmacokinetics of tacrine.
Tacrine is currently the only treatment approved for use in Alzheimer's disease. There is, however, considerable debate over its effectiveness due to conflicting clinical trial results. Most investigators agree, nevertheless, that a definite sub-population of patients do benefit from therapy with tacrine. Tacrine is associated with large pharmacokinetic interindividual variation within both patient and control groups. This is thought to influence both the efficacy and incidence of symptomatic adverse effects in individual patients. Following oral administration of tacrine the drug is rapidly and well absorbed with peak plasma concentrations (Cmax) achieved within 0.5 to 3 hours (after a single dose of 20 to 50mg). Tacrine appears to have a wide tissue distribution, which is reflected by its large volume of distribution. High concentrations of the drug were found in the kidney, liver, adrenal gland and brain tissue in animal models. It has a low bioavailability following oral intake, thought to result from extensive first-pass metabolism. Bioavailability can be increased upon rectal administration. The drug is rapidly and extensively metabolised in humans. In vitro metabolism studies have demonstrated the importance of cytochrome P450 (CYP1A2) in the biotransformation of tacrine to 1-, 2-, 4- and 7-hydroxylated metabolites. In humans, mono- and dihydroxylated tacrine and glucuronide conjugates were identified in the urine, which was the primary route of excretion. The elimination half-life of tacrine was short, 1.5 to 2.5 hours after single oral and intravenous doses and 2.9 to 3.6 hours after multiple oral doses. At low doses (10mg) of tacrine, the pharmacokinetic profile was nonlinear and the oral bioavailability of the drug was disproportionately low in comparison to higher doses of tacrine (20mg).(ABSTRACT TRUNCATED AT 250 WORDS)


Cognitive, psychosocial, and educational issues in neuromuscular disease.
There is a broad range of cognitive function in persons with neuromuscular disease, both between and within the various types. Those groups exhibiting little or no cognitive impairment included FSHD, LGS, BMD, SMA, and HMSN. DMD and MD--particularly C-MD-groups did show deficits. The data on HSCA are too minimal to reach any firm conclusion at this time. Specific patterns of deficits in DMD have been proposed, but need further research. No specific correlates with diminished intellectual function have yet been found, and the search for a cause of the intellectual deficit has as yet been unsuccessful. Nevertheless, the impact of NMD on psychosocial and educational function of both children and adults is significant. It is recommended that supportive services be provided by medical professionals specifically trained in such helping professions as psychology to lessen the impact of these chronic progressive diseases and thus to improve the quality of life of persons with NMD.


Intraosseous transfusion of hemoglobin vesicles in the treatment of hemorrhagic shock with collapsed vessels in a rabbit model.
Intravenous transfusion sometimes encounters difficulty under prehospital conditions when peripheral vessels are collapsed and inaccessible. We investigated whether the cellular type hemoglobin-based oxygen carriers (Hemoglobin Vesicles: HbVs) allow intraosseous administration into blood circulation for the resuscitation of rabbits with severe hemorrhagic shock. New Zealand white rabbits (2.5 kg average) were set in severe hemorrhagic shock [mean arterial pressure (MAP): 21 ± 2 mm Hg, Hb 5.1 ± 0.8 g/dL]. Immediately thereafter, 12 mL/kg of HbVs, 5% human serum albumin (HSA), autologous whole blood (WB), stored red blood cells (RBCs) or 36 mL/kg of Lactated Ringer's (LR) were intraosseously transfused, followed by an additional intraosseous transfusion with 8 mL/kg of HSA (following HbV, HSA or stored RBC transfusion), or WB or 24 mL/kg of LR (following LR transfusion), respectively. Intraosseous transfusion of HbVs increased MAP (48 ± 9 mm Hg) and improved hypohemoglobinemia (7.1 ± 0.6 g/dL) as well as WB or RBC transfusion. In contrast, neither HSA nor LR improved hemodynamics or Hb levels. Seven out of 10 rabbits receiving HbVs survived for 24 hours, while only one out of 10 rabbits receiving LR survived (WB and RBC; 100% survivals, HSA; 30% survival). Intraosseous infusion of HbVs might be an effective initial treatment to maintain hemodynamics during acute hemorrhagic shock. This approach could be used in emergency situations in which access to peripheral vessels is difficult.


Mechanistic and kinetic study on the ozonolysis of n-butyl vinyl ether, i-butyl vinyl ether and t-butyl vinyl ether.
Density functional theory (DFT) and ab initio method are employed to elucidate the mechanisms for O(3)-initiated oxidation of n-butyl vinyl ether (n-BVE) and its isomers (i-BVE and t-BVE). For each BVE, the reactions proceed via O(3) cycloaddition resulting in the formation of primary ozonides (POZs) and then two self-decomposition pathways of POZs are followed. Major products are identified to be formaldehyde and butyl formates (CH(3)CH(2)CH(2)CH(2)OCHO for n-BVE, (CH(3))(2)CHCH(2)OCHO for i-BVE and (CH(3))(3)COCHO for t-BVE). The total and individual rate constants for main product channels have been calculated using the modified multichannel Rice-Ramsperger-Kassel-Marcus (RRKM) approach. At 298 K and 101 kPa, the calculated total rate constants are 2.50×10(-16), 3.41×10(-16) and 4.17×10(-16) cm(3) molecule(-1) s(-1) for n-BVE+O(3), i-BVE+O(3) and t-BVE+O(3), respectively, which are in perfect agreement with experimental results. The total rate coefficients are almost pressure independent in the range of 0.001-101 kPa but obviously positive temperature dependent over the whole study temperature range (200-400 K). Also, the favorable reaction pathways have been determined through the estimation of branching ratios. Moreover, the influence of alkoxy group structure on the reactivity of vinyl ethers was examined.


Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis.
Myocardial fibrosis alters the cardiac architecture favouring the development of cardiac dysfunction, including arrhythmias and heart failure. Reducing myocardial fibrosis may improve outcomes through the targeted diagnosis and treatment of emerging fibrotic pathways. The European-Commission-funded 'FIBROTARGETS' is a multinational academic and industrial consortium with the main aims of (i) characterizing novel key mechanistic pathways involved in the metabolism of fibrillary collagen that may serve as biotargets, (ii) evaluating the potential anti-fibrotic properties of novel or repurposed molecules interfering with the newly identified biotargets, and (iii) characterizing bioprofiles based on distinct mechanistic phenotypes involving the aforementioned biotargets. These pathways will be explored by performing a systematic and collaborative search for mechanisms and targets of myocardial fibrosis. These mechanisms will then be translated into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure. The FIBROTARGETS consortium has merged data from 12 patient cohorts in a common database available to individual consortium partners. The database consists of >12 000 patients with a large spectrum of cardiovascular clinical phenotypes. It integrates community-based population cohorts, cardiovascular risk cohorts, and heart failure cohorts. The FIBROTARGETS biomarker programme is aimed at exploring fibrotic pathways allowing the bioprofiling of patients into specific 'fibrotic' phenotypes and identifying new therapeutic targets that will potentially enable the development of novel and tailored anti-fibrotic therapies for heart failure.


Cartilage in normal and osteoarthritis conditions.
The preservation of articular cartilage depends on keeping the cartilage architecture intact. Cartilage strength and function depend on both the properties of the tissue and on their structural parameters. The main structural macromolecules are collagen and proteoglycans (aggrecan). During life, cartilage matrix turnover is mediated by a multitude of complex autocrine and paracrine anabolic and catabolic factors. These act on the chondrocytes and can lead to repair, remodeling or catabolic processes like those that occur in osteoarthritis. Osteoarthritis is characterized by degradation and loss of articular cartilage, subchondral bone remodeling, and, at the clinical stage of the disease, inflammation of the synovial membrane. The alterations in osteoarthritic cartilage are numerous and involve morphologic and metabolic changes in chondrocytes, as well as biochemical and structural alterations in the extracellular matrix macromolecules.


SOX7 is associated with the suppression of human glioma by HMG-box dependent regulation of Wnt/β-catenin signaling.
SOX7 has been recently recognized as a tumor suppressor belonging to the SOX (SRY-related HMG-box) family of a transcription factor. However, its role in human gliomas is unknown. Our study showed that SOX7 expression was significantly downregulated in human gliomas. Statistical analysis showed that SOX7 suppression was associated with higher histological grades of tumors in glioma tissues. SOX7 could suppress tumor properties both in vivo and in vitro, and depletion of the HMG domain abolishes its tumor suppressive roles. In vitro assays demonstrated that SOX7 could downregulate Wnt/β-catenin transcription and decrease the expression of Cyclin D1 and c-Myc, while the mutant SOX7 lost these functions. These results suggested that the HMG-box is a key domain of SOX7 for negatively regulating the Wnt/β-catenin signaling pathway when functioning as a tumor suppressor in a glioma.


A review of evidence leading to the prediction that 1,4-butanediol is not a carcinogen.
1,4-Butanediol is an industrial chemical used primarily as an intermediate in the manufacture of other organic chemicals. It has recently been associated with deaths, addiction and withdrawal related to its promotion and use as a dietary supplement. The rapid absorption and conversion of 1,4-butanediol to gamma-hydroxybutyric acid (GHB, or date rape drug) in animals and humans is well documented and is the basis for its abuse potential. A disposition and metabolism study conducted in F344 rats by the National Toxicology Program (NTP) confirmed the rapid conversion of 1-(14)C-1,4-butanediol to (14)CO2. Because of this, the toxicological profile of 1,4-butanediol resembles that of gamma-hydroxybutyric acid. Gamma-hydroxybutyric acid occurs naturally in the brain and peripheral tissues and is converted to succinate and metabolized through the TCA cycle. Although the function of gamma-hydroxybutyric acid in peripheral tissues is not known, the presence of specific high affinity receptors for gamma-hydroxybutyric acid suggests that it functions as a neuromodulator in the brain and neuronal tissue. Gamma-hydroxybutyric acid readily crosses the blood-brain barrier and elicits characteristic neuropharmacologic responses after oral, i.p., or i.v. administration. The same responses are observed after administration of 1,4-butanediol. The cyclic lactone of gamma-hydroxybutyric acid, gamma-butyrolactone, is also rapidly converted to gamma-hydroxybutyric acid by enzymes in the blood and liver in animals and humans, and produces pharmacological effects identical to those produced by 1,4-butanediol and gamma-hydroxybutyric acid. Gamma-butyrolactone was previously evaluated by the NTP in 14-day and 13-week prechronic toxicology studies and in 2-year chronic toxicology and carcinogenesis studies in F344 rats and B6C3F1 mice. No organ specific toxicity occurred. In the carcinogenesis studies there was an equivocal response in male mice based on a marginal increase in the incidence of pheochromocytomas of the adrenal medulla. Because the absence of chronic toxicity and significant carcinogenicity of gamma-hydroxybutyric acid were established in NTP prechronic and chronic studies with gamma-butyrolactone, it is concluded that similar results would be obtained in a 2-year study with 1,4-butanediol, and that 1,4-butanediol is not a carcinogen.


Superoxide dismutases in malignant cells and human tumors.
Reactive oxygen metabolites have multifactorial effects on the regulation of cell growth and the capacity of malignant cells to invade. Overexpression of the superoxide dismutases (SODs) in vitro increases cell differentiation, decreases cell growth and proliferation, and can reverse a malignant phenotype to a nonmalignant one. The situation in vivo is more complex due to multiple interactions of tumor cells with their environment. Numerous in vivo studies show that the superoxide dismutases can be highly expressed in aggressive human solid tumors. Furthermore, high SOD has occasionally been associated with a poor prognosis and with resistance to cytotoxic drugs and radiation. Most of the apparent conflicts between the above in vitro and in vivo observations can be reconciled by considering the net redox status of tumor cells in different environments. Administering high concentrations of SOD to cells in vitro is usually associated with a non- or less malignant phenotype, whereas secondary induction of SOD in tumors in vivo can be associated with an aggressive malignant transformation probably due to the altered (oxidative) redox state in the malignant cells. This concept suggests that for many types of tumors antioxidants could be used to diminish the invasive capability of malignant cells.


Phylogenetic constraints and adaptation explain food-web structure.
Food webs are descriptions of who eats whom in an ecosystem. Although extremely complex and variable, their structure possesses basic regularities. A fascinating question is to find a simple model capturing the underlying processes behind these repeatable patterns. Until now, two models have been devised for the description of trophic interactions within a natural community. Both are essentially based on the concept of ecological niche, with the consumers organized along a single niche dimension; for example, prey size. Unfortunately, they fail to describe adequately recent and high-quality data. Here, we propose a new model built on the hypothesis that any species' diet is the consequence of phylogenetic constraints and adaptation. Simple rules incorporating both concepts yield food webs whose structure is very close to real data. Consumers are organized in groups forming a nested hierarchy, which better reflects the complexity and multidimensionality of most natural systems.


Cadaveric study identifying clinical sonoanatomy for proximal and distal approaches of ultrasound-guided intercostobrachial nerve block.
The intercostobrachial nerve (ICBN) has significant anatomical variation. Localization of the ICBN requires an operator's skill. This cadaveric study aims to describe two simple ultrasound-guided plane blocks of the ICBN when it emerges at the chest wall (proximal approach) and passes through the axillary fossa (distal approach). The anatomical relation of the ICBN and adjacent structures was investigated in six fresh cadavers. Thereafter, we described two potential techniques of the ICBN block. The proximal approach was an injection medial to the medial border of the serratus anterior muscle at the inferior border of the second rib. The distal approach was an injection on the surface of the latissimus dorsi muscle at 3-4 cm caudal to the axillary artery. The ultrasound-guided proximal and distal ICBN blocks were performed in seven hemithoraxes and axillary fossae. We recorded dye staining on the ICBN, its branches and clinically correlated structures. All ICBNs originated from the second intercostal nerve and 34.6% received a contribution from the first or third intercostal nerve. All ICBNs gave off axillary branches in the axillary fossa and ran towards the posteromedial aspect of the arm. Following the proximal ICBN block, dye stained on 90% of all ICBN's origins. After the distal ICBN block, all terminal branches and 43% of the axillary branches of the ICBN were stained. The proximal and distal ICBN blocks, using easily recognized sonoanatomical landmarks, provided consistent dye spread to the ICBN. We encourage further validation of these two techniques in clinical studies.


AMPK-mTOR-Mediated Activation of Autophagy Promotes Formation of Dormant Polyploid Giant Cancer Cells.
Dormant cancer cells that survive anticancer therapy can lead to cancer recurrence and disseminated metastases that prove fatal in most cases. Recently, specific dormant polyploid giant cancer cells (PGCC) have drawn our attention because of their association with the clinical risk of nasopharyngeal carcinoma (NPC) recurrence, as demonstrated by previous clinical data. In this study, we report the biological properties of PGCC, including mitochondrial alterations, and reveal that autophagy is a critical mechanism of PGCC induction. Moreover, pharmacologic or genetic inhibition of autophagy greatly impaired PGCC formation, significantly suppressing metastasis and improving survival in a mouse model. Mechanistically, chemotherapeutic drugs partly damaged mitochondria, which then produced low ATP levels and activated autophagy via the AMPK-mTOR pathway to promote PGCC formation. Analysis of the transcriptional and epigenetic landscape of PGCC revealed overexpression of RIPK1, and the scaffolding function of RIPK1 was required for AMPK-mTOR pathway-induced PGCC survival. High numbers of PGCCs correlated with shorter recurrence time and worse survival outcomes in patients with NPC. Collectively, these findings suggest a therapeutic approach of targeting dormant PGCCs in cancer. Pretreatment with an autophagy inhibitor before chemotherapy could prevent formation of therapy-induced dormant polyploid giant cancer cells, thereby reducing recurrence and metastasis of nasopharyngeal carcinoma.


Anti-carcinogenic activity of 6-methylsulfinylhexyl isothiocyanate-, an active anti-proliferative principal of wasabi (Eutrema wasabi Maxim.).
Synthetic 4-methylsulfinylhexyl isothiocyanate (MITC)(a potent inducer of phase 2 detoxification enzymes from broccoli) and 6-MITC(a potent anti-proliferative principal from wasabi) slightly inhibited the induction of mouse skin tumor in a two-stage process of carcinogenesis (initiator, 9,10-dimethyl-1,2-benzanthracene; promotor,12-o-tetradecanoylphorbol-13-acetate), but the effect was not significant. Both compounds, however, significantly inhibited the mutation of skin resulting from topical applications of the carcinogens. When a murine hepatoma cell line, Hepa 1c1c7, was treated with 2-,4-,6- and 8-MITCs, they augmented the induction of its quinone reductase, one of the phase 2 detoxification enzymes in a concentration dependent manner, and the 4- and 6-MITCs were much more potent on the reduction of the enzyme than the 2- and 8-MITCs. All 2-, 4-, 6- and 8-MITCs suppressed the growth of murine tumor cells, their suppressive activities being proportional to the length of their methyl residue. They were also cytotoxic to mouse peritoneal exudate macrophages which were not proliferating in vitro, indicating that the cellular targets of isothiocyanate may not be dependent upon the cell cycle. In addition, all the 2-, 4-, 6- and 8-MITCs inhibited the production of nitric oxide (a potent radical carcinogen) by peritoneal macrophages.


Uniportal versus multiportal video-assisted thoracoscopic anatomical resection for NSCLC: a meta-analysis.
Uniportal video-assisted thoracoscopic surgery (U-VATS) has recently emerged as an alternative procedure for non-small cell lung cancer (NSCLC); however, whether U-VATS has advantages over multiportal VATS (M-VATS) remains unknown. We performed a systematic review of two databases (Pubmed and Web of Science) to search comparative studies of U-VATS and M-VATS anatomical pulmonary resection for NSCLC. Operative time, blood loss, number of resected lymph nodes, drainage duration, length of postoperative stay, pain in postoperative day 1(POD1) and conversion rates were retrieved to estimate the comparison of outcomes. A subgroup analysis stratified by study type (propensity-matched analysis and randomized-controlled trial versus non-propensity matched analysis) was performed. A total of 20 studies with 4142 patients were included in this meta-analysis. U-VATS was performed on 1869 patients, whereas the other 2173 patients underwent M-VATS. This meta-analysis showed that there was no significant difference in operative time (U-VATS: 146.48 ± 55.07 min versus M-VATS: 171.70 ± 79.40 min, P = 0.81), blood loss (74.49 ± 109.03 mL versus 95.48 ± 133.67 mL, P = 0.18), resected lymph nodes (17.28 ± 9.46 versus 18.31 ± 10.17, P = 0.62), conversion rate (6.18% versus 4.34%, P = 0.14), drainage duration (3.90 ± 2.94 days versus 4.44 ± 3.12 days, p = 0.09), length of postoperative stay (6.16 ± 4.40 days versus 6.45 ± 4.80 days, P = 0.22), and pain in POD1 (3.94 ± 1.68 versus 3.59 ± 2.76, p = 0.07). Subgroup analysis showed the value of PSM and RCT group consistency with overall value. This up-to-date meta-analysis shows that the perioperative outcomes of U-VATS and M-VATS anatomical pulmonary resection are equivalent. In addition, the differences in long-term outcomes of these two approaches are still unclear. Thoracic surgeons should pay more emphasize on providing high-quality and personalized surgical care for patients, to improve the survival ultimately.


[Redefinition of myocardial infarction--relevance of biomarkers].
Myocardial infarction (MI) as an acute and life-threatening complication of coronary heart disease is one of the most frequent causes of death in Germany. Therefore, diagnosis, risk stratification and treatment of acute MI are of great clinical relevance. Specific recommendations concerning diagnosis of acute MI can be found in current guidelines of the European Society of Cardiology (ESC) and the German Cardiac Society, as well as in a consensus document "Universal definition of myocardial infarction", which has been published at the end of 2007. Here, cardiac markers, namely cardiac troponins, play a central role as a criterion for the diagnosis of myocardial infarction. Moreover, cardiac troponins provide prognostic information and are of great value for risk stratification of patients. Measurement of creatine kinase CK-MB is an alternative to troponin measurement, but is only recommended, if troponins are not available. As a cutoff value for cardiac biomarkers the 99th percentile of a healthy reference population has been defined. However, assays that are used for routine testing require adequate precision. Besides established biomarkers, several novel markers have been evaluated in clinical studies in recent years. Especially B-type natriuretic peptides (BNP and NT-proBNP) and C-reactive protein (CRP) have gained great interest and sufficient data has been gathered, justifying clinical application of these novel markers. As a consequence, BNP/NT-proBNP and CRP are mentioned in the current guidelines of the ESC as appropriate biomarkers for risk stratification. The clinical relevance of other novel biomarkers remains uncertain and necessitates further studies.


Estimating tuberculosis cases and their economic costs averted in the United States over the past two decades.
Following a concerted public health response to the resurgence of tuberculosis (TB) in the United States in the late 1980s, annual TB incidence decreased substantially. However, no estimates exist of the number and cost savings of TB cases averted. TB cases averted in the United States during 1995-2014 were estimated: Scenario 1 used a static 1992 case rate; Scenario 2 applied the 1992 rate to foreign-born cases, and a pre-resurgence 5.1% annual decline to US-born cases; and a statistical model assessed human immunodeficiency virus and TB program indices. We applied the cost of illness to estimate the societal benefits (costs averted) in 2014 dollars. During 1992-2014, 368 184 incident TB cases were reported, and cases decreased by two thirds during that period. In the scenarios and statistical model, TB cases averted during 1995-2014 ranged from approximately 145 000 to 319 000. The societal benefits of averted TB cases ranged from US$3.1 to US$6.7 billion, excluding deaths, and from US$6.7 to US$14.5 billion, including deaths. Coordinated efforts in TB control and prevention in the United States yielded a remarkable number of TB cases averted and societal economic benefits. We illustrate the value of concerted action and targeted public health funding.


Successful treatment of Chlamydophila pneumoniae acute respiratory distress syndrome with extracorporeal membrane oxygenator: a case report and diagnostic review.
Chlamydophila pneumoniae is a respiratory pathogen known to infect the upper and lower respiratory tracts. Infection severity can range from sub-clinical pulmonary infection to acute respiratory distress syndrome. A previously healthy 62-year-old Caucasian man was admitted to our hospital for acute respiratory failure. Serum samples obtained every week starting from the day of admission showed clear-cut seroconversion for C. pneumoniae antibodies. All other cultures obtained during the first days of hospitalization were negative. Despite maximal ventilatory support (high positive end expiratory pressure, fraction of inspired oxygen of 1.0, nitric oxide inhalation, neuromuscular blocking agents and prone positioning), our patient remained severely hypoxemic, which led us to initiate an extracorporeal membrane oxygenation treatment. Extracorporeal membrane oxygenation and hemodiafiltration were withdrawn on day 12. Our patient was extubated on day 18 and discharged from our Intensive Care Unit on day 20. He went home a month later. We describe the first published case of acute respiratory distress syndrome due to C. pneumoniae infection successfully treated by extracorporeal membrane oxygenation, a very useful tool in this syndrome. A quick and specific method for the definite diagnosis of Chlamydophila infection should be developed.


β-asarone prolongs sleep via regulating the level of glutamate in the PVN.
People of all ages could suffer from sleep disorders, which are increasingly recognized as common manifestations of neurologic disease. Acorus tatarinowii is a herb that has been used in traditional medicine to promote sleep. β-asarone, as the main component of volatile oil obtained from Acorus tatarinowii, may be the main contributor to the sleeping-promoting efficacy of Acorus tatarinowii. In the study, adult male C57BL/6 mice were administered β-asarone at 12.5 mg/kg, 25 mg/kg, and 50 mg/kg. Behavioral experiments showed that β-asarone at 25 mg/kg could significantly improve sleep duration. It was also observed that the proportion of NREM (Non-Rapid Eye Movement) sleep increased considerably after administration of β-asarone. In the PVN (paraventricular nucleus of hypothalamus) region of the hypothalamus, it was observed that the glutamate content decreased after β-asarone treatment. At the same time, the expression of VGLUT2 (vesicular glutamate transporters 2) decreased while the expression of GAD65 (glutamic acid decarboxylase 65) and GABARAP (GABA Type A Receptor-Associated Protein) increased in the hypothalamus, suggesting that β-asarone may suppress arousal by reducing glutamate and promoting transformation of glutamate to the inhibitory neurotransmitter GABA (γ-aminobutyric acid). This study is the first to focus on the association between β-asarone and sleep, shedding perspectives for pharmacological applications of β-asarone and providing a new direction for future research.


Clinical testing of Amipaque for cerebral angiography.
Amipaque 280 mg I/ml was compared to Isopaque Cerebral 280 mg I/ml for common carotid injection in twenty patients in a double blind trial. Simple comparison was also performed in examinations with selective external carotid injections. The reaction of the patients to the common carotid injection was mild on the whole but Amipaque caused significantly less discomfort than Isopaque. Selective external carotid injection of Amipaque caused very little discomfort while most patients complained of severe pain when Isopaque was used. No serious side-effect was observed.


Effects of Different Amounts of Supplemental Selenium and Vitamin E on the Incidence of Retained Placenta, Selenium, Malondialdehyde, and Thyronines Status in Cows Treated with Prostaglandin F2α for the Induction of Parturition.
The incidence of retained placenta (RP) in cows increases in cases of parturition induced by prostaglandin F2α . We analyzed the effects of different doses of supplemental selenium and vitamin E on the incidence of RP, blood selenium, plasma thyronines, and malondialdehyde concentration. Thirty-three clinically healthy, multiparous Holstein-Frisian cows were assigned to 3 groups and supplemented with a single intramuscular injection of sodium selenite (SS) and tocopherol acetate (TAc) between days 250 to 255 of gestation: control-unsupplemented; group A-10 mg SS + 400 mg TAc; group B-20 mg SS + 800 mg TAc. Parturition was induced using PGF2α not before day 275 of gestation. The RP incidence was reduced from 66.7% in the control to 38.2 and 30.8% in groups A and B, respectively. Blood selenium and glutathione peroxidase activity in treated groups were significantly higher compared to control, with no significant difference between groups A and B. Plasma malondialdehyde in group B was significantly lower than that in control and group A, while thyronines levels were not affected. Comparison of RP and non-RP cows, independently of supplement treatment, revealed higher blood selenium and glutathione peroxidase activity and lower MDA and thyroxine in non-RP animals, while triiodothyronine level did not differ.


Distal rectoanal excitatory reflex: a reliable index of pudendal neuropathy?
Denervation of the extrinsic anal sphincter and pudendal neuropathy are confirmed by electrophysiologic or electromyographic testing, techniques that may not be available universally and require special equipment and training. A simple manometric test that is easy to perform and complements existing studies was performed to confirm pudendal neuropathy. Fourteen patients with excessive defecatory straining and 30 patients with idiopathic fecal incontinence were studied by electrophysiology and balloon reflex manometry. Pudendal nerve terminal motor latency (PNTML) and rectoanal excitatory reflex were evaluated for abnormalities. Results were compared with 20 controls who had no anorectal complaints and who had similar testing performed. In controls, PNTML was normal in all but one person. Rectoanal excitatory reflex could be elicited in all controls with either 20 or 40 ml of air. Four different types of balloon reflex responses were observed in patient groups: diminutive excitation, delayed excitation, excitation at high volume of distention only, and absent excitation. Ten patients with fecal incontinence had normal PNTML but abnormal distal excitatory reflex, 5 patients had abnormal PNTML but normal distal excitatory reflex, and 15 patients had both PNTML and excitatory reflex that were abnormal. In patients with excessive defecatory straining, results of both tests were abnormal in six patients, and eight patients had abnormal excitatory reflex but normal PNTML. Pudendal neuropathy may result in abnormalities of excitatory reflex morphology or other characteristics. Abnormal distal excitatory reflex may complement electrophysiologic findings or may serve as a suitable alternative to confirm pudendal neuropathy in centers where facilities for formal testing are not available.


Engineering interventions in industrial filamentous fungal cell factories for biomass valorization.
Filamentous fungi possess versatile capabilities for synthesizing a variety of valuable bio compounds, including enzymes, organic acids and small molecule secondary metabolites. The advancements of genetic and metabolic engineering techniques and the availability of sequenced genomes discovered their potential as expression hosts for recombinant protein production. Remarkably, plant-biomass degrading filamentous fungi show the unique capability to decompose lignocellulose, an extremely recalcitrant biopolymer. The basic biochemical approaches have motivated several industrial processes for lignocellulose biomass valorisation into fermentable sugars and other biochemical for biofuels, biomolecules, and biomaterials. The review gives insight into current trends in engineering filamentous fungi for enzymes, fuels, and chemicals from lignocellulose biomass. This review describes the variety of enzymes and compounds that filamentous fungi produce, engineering of filamentous fungi for biomass valorisation with a special focus on lignocellulolytic enzymes and other bulk chemicals.


Hearing disability in childhood--a cross-sectional and longitudinal investigation of causative factors.
This contribution describes and compares the causes of hearing disability in a cohort of children, born 1980-90, provided with hearing aids and included into the longitudinal surveillance programs of hearing-disabled children performed in two pediatric audiological units within the Copenhagen area. In addition the causes of hearing disability in childhood are compared with the causes found in a cohort born 1970-80, within the same geographical area, using the same criteria for hearing disability and diagnostic classification. No significant differences in the etiology of hearing disability were present in the two districts, and in the combined area prenatal causes accounted for 55% with inheritance (46%) being the most prominent cause of hearing disability. A significant increase in the incidence of inherited hearing disability among the prenatal causes from 69% in the 1970-80 cohort to 85% in the 1980-90 cohort was demonstrated, while a significant decrease in the incidence of foetal infection (i.e. rubella) from 27% to 9% within the two decades was demonstrated. No significant changes in the perinatal and postnatal causes were found from the 1970-80 to 1980-90 cohort, and although an improvement in the diagnostic procedures was found--i.e. a reduction from 26% to 20% in the incidence of unknown cause--the difference in the incidence of unknown cause is insignificant between the two decades. The investigation supports the need for continuous monitoring of the causes of hearing disability in childhood and supports the potential value of worldwide accepted criteria for etiological categories.


Reconstruction of anterior mitral leaflet using autologous pericardial patch combined with posterior leaflet sliding for active infective endocarditis.
We report a case of active infective endocarditis in a young adult, affecting the anterior and posterior leaflets extensively. The patient underwent a mitral valve repair with extended sliding repair on the posterior leaflet and reconstruction using an autologous pericardial patch supported by an artificial chord on the anterior leaflet. Although we finally needed commissure closing for successful repair, we aggressively achieved a repair-oriented strategy using several techniques in a young patient who may have required mitral valve replacement.


A morphologic study of the submucosa of the large intestine.
The morphologic structure of human, rat and mouse submucosa is similar. The strength, natural tension and extensibility of the submucosa can be readily interpreted form the physical properties of collagen and its structural arrangement as a pliable honeycomb. The perforations allow blood and lymph vessels to reach the mucosa.


Closure of tympanic membrane perforations by the use of fat.
Otologists have attempted to close tympanic membrane perforations for 300 years. It has been in the past 25 years that closure with autograft materials has been consistently successful. Homografts have been successful for the past 10 years. One of the autograft materials, ear lobe fat, has been in use for the past 15 years. Over this period 65 patients have been reviewed. This report reviews the literature, explains the technique and summarizes the results as to hearing, graft mobility and graft survival.


Familial malrotation: report of three affected siblings.
We herein report the case of three siblings presenting with intestinal malrotation. Their medical history and circumstances of diagnosis are described. Barium meal demonstrated a minor duodenal anomaly in the mother. As far as we can ascertain, this is the third report of isolated familial malrotation in more than one generation, raising questions about its developmental mechanism. We thus highlight in what circumstances familial investigations should be undertaken in case of malrotation.


A machine learning framework for risk prediction of multi-label cardiovascular events based on focused carotid plaque B-Mode ultrasound: A Canadian study.
Machine learning (ML) algorithms can provide better cardiovascular event (CVE) prediction. However, ML algorithms are mostly explored for predicting a single CVE at a time. The objective of this study is to design and develop an ML-based system to predict multi-label CVEs, such as (i) coronary artery disease, (ii) acute coronary syndrome, and (iii) a composite CVE-a class of AtheroEdge 3.0 (ML) system. Focused carotid B-mode ultrasound and coronary angiography are performed on a group of 459 participants consisting of three cardiovascular labels. Initially, 23 risk predictors comprising (i) patients' demographics, (ii) clinical blood-biomarkers, and (iii) carotid ultrasound image-based phenotypes are collected. Six types of classification techniques comprising (a) four problem transformation methods (PTM) and (b) two algorithm adaptation methods (AAM) are used for multi-label CVE prediction. The performance of the proposed system is evaluated for accuracy, sensitivity, specificity, F1-score, and area-under-the-curve (AUC) using 10-fold cross-validation. The proposed system is also verified using another database of 522 participants. For the primary database, PTM demonstrated a better multi-label CVE prediction than AAM (mean accuracy: 80.89% vs. 62.83%, mean AUC: 0.89 vs. 0.63), validating our hypothesis. The PTM-based binary relevance (BR) technique provided optimal performance in multi-label CVE prediction. The overall multi-label classification accuracy, sensitivity, specificity, F1-score, and AUC using BR are 81.2 ± 3.01%, 76.5 ± 8.8%, 83.8 ± 3.8%, 75.37 ± 5.8%, and 0.89 ± 0.02 (p < 0.0001), respectively. When used on the second Canadian database with seven cardiovascular events (acute coronary syndrome, myocardial infarction, angina, stroke, transient ischemic attack, heart failure, and death), the proposed system showed an accuracy of 96.36 ± 0.87% (AUC: 0.61 ± 0.06, p < 0.0001). ML-based multi-label classification algorithms, such as binary relevance, yielded the best predictions for three cardiovascular endpoints.


Association of insulin-like growth factor-binding protein-3 with radiotherapy response and prognosis of esophageal squamous cell carcinoma.
Insulin-like growth factor-binding protein-3 (IGFBP-3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma (ESCC). The present study was designed to investigate the clinical and prognostic effects of IGFBP-3 on ESCC. IGFBP-3 was detected by immunohistochemistry in paraffin-embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non-malignant esophageal specimens. Receiver operating characteristic (ROC) analysis was used to determine cut-off scores for tumor positivity and to evaluate patient survival status. The χ(2) test was performed to analyze the association of IGFBP-3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP-3 expression were investigated using Kaplan-Meier analysis and the Cox proportional hazards model. The threshold for IGFBP-3 positivity was set to greater than 65% [area under the ROC curve (AUC)=0.690, P<0.019]. Of the 70 ESCC patient tissues tested, 32 (45.7%) were defined as having high IGFBP-3 expression. The levels of IGFBP-3 protein expression were decreased in 70.0% (7 of 10) of ESCC tissues compared with adjacent non-malignant esophageal tissue. In addition, IGFBP-3 expression was associated with pathologic classification (P<0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP-3 in the tumor had an improved radiotherapy response and prolonged overall survival (P<0.001). High level of IGFBP-3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy.


Computational insights into the binding modes of Sr-Rex with cofactor NADH/NAD+ and operator DNA.
The transcriptional repressor Rex plays key roles in modulating respiratory gene expression. It senses the redox poise of the NAD(H) pool. Rex from Streptomyces rimosus (Sr-Rex) is a newly identified protein. Its structure and complex with substrates are not determined yet. In this study, the three-dimensional (3D) structural models of Sr-Rex dimer and its complex with cofactors were constructed by homology modeling. The stability of the constructed Sr-Rex models and the detailed interactions between Sr-Rex and cofactors were further investigated by molecular dynamics simulations. The results demonstrated that the conformation of Sr-Rex changed a lot when binding with the reduced NADH or oxidized NAD(+). Once binding with NADH, the Sr-Rex dimer displayed an opener conformation, which would weaken the interaction of Sr-Rex with Rex operator DNA (ROP). Key residues responsible for the binding were then identified. The computational results were consistent with experimental results, and hence provided insights into the molecular mechanism of Sr-Rex binding with ROP and NADH/NAD(+), which might be helpful for the development of biosensor.


alpha-Dystrobrevin isoforms differ in their colocalization with and stabilization of agrin-induced acetylcholine receptor clusters.
In skeletal muscle, alpha-dystrobrevin (alphaDB) is expressed throughout the sarcolemma with high concentrations at the neuromuscular junction. Mice lacking alphaDB display a mild muscular dystrophy and perturbations at the neuromuscular junction that include disruptions to acetylcholine receptor (AChR) cluster stability and patterning. In adult skeletal muscle, three alternatively spliced isoforms (alphaDB1, alphaDB2, alphaDB3) are expressed, while two other splice variants (alphaDB1(-) and alphaDB2(-)) are expressed only during early development. alphaDB is clearly important in AChR stabilization; however, the degree to which individual alphaDB isoforms and their specific functional domains contribute to AChR cluster stability is not fully understood. To investigate this, we established a primary muscle cell culture system from alphaDB knockout mice and stably expressed individual alphaDB isoforms using retroviral infection. A comparison between wild-type and alphaDB knockout muscle cells showed that in the absence of alphaDB, fewer AChR clusters formed in response to agrin treatment, and these AChR clusters were very unstable. Retroviral expression studies revealed that the largest isoforms (alphaDB1, alphaDB1(-), alphaDB2, alphaDB2(-)) colocalized with agrin-induced AChR clusters and rescued the AChR cluster formation defects back to wild-type levels, while only the first three isoforms fully rescued AChR cluster stability back to wild-type levels. alphaDB2(-) conferred an intermediate level of stability to the AChR clusters. In contrast, alphaDB3 showed no specific colocalization with AChR clusters and little effect on AChR cluster formation or stabilization. Twice as much syntrophin was found associated with alphaDB2 compared with alphaDB2(-) in myotubes suggesting that increased recruitment of syntrophin by alphaDB may enhance the stability of AChR clusters. Taken together, these data demonstrate that different alphaDB isoforms have different functional capabilities in the formation and maintenance of AChR clusters in muscle cells, and that these differences are likely due to the presence of different functional domains in each isoform.


Soil bioremediation by Pseudomonas brassicacearum MPDS and its enzyme involved in degrading PAHs.
Polycyclic aromatic hydrocarbons (PAHs) commonly coexist in contaminated sites, posing a significant threat to ecosystem. Strains that degrade a wide range of substrates play important roles in bioremediation of contaminated environment. In this study, we reveal that Pseudomonas brassicacearum MPDS was able to remove 31.1% naphthalene of 500 mg/kg from soil within 2 d, while its relative abundance decreased significantly on Day 20, indicating its applicable potential in soil remediation. In addition to naphthalene, dibenzofuran, dibenzothiophene, and fluorene as reported previously, strain MPDS is able to degrade carbazole, phenanthrene, pyrene, and 2-bromonaphthalene. Moreover, NahA from strain MPDS has multi-substrate catalytic capacities on naphthalene, dibenzofuran, dibenzothiophene, phenanthrene, and 2-bromonaphthalene into dihydrodiols, while converts fluorene and carbazole into monohydroxy compounds according to GC-MS analysis. This study provides further insights into the exploration of soil remediation by strain MPDS and the mining of enzymes involved in the degradation of PAHs.


Phosphorus-31 MR spectroscopy of normal adult human brain and brain tumours.
Localized phosphorus-31 MR spectra were obtained in vivo in a large series of normal human brain tissue specimens of healthy volunteers (n=36) and various brain tumours (n=52). Tumour types examined included grade II and grade III gliomas (n=15 and n=1, respectively), glioblastomas (n=16) and meningeomas (n=12). An additional eight tumours were analysed during chemo- or radiotherapy. Spectra were acquired using a modified ISIS pulse sequence with a repetition time of 3 s. Voxel sizes ranged from 56 to 129 ml. The spectra were evaluated using a least-square variable projection (VARPRO) fitting procedure in the time domain, which allows semi-quantitative determination of relative metabolite concentrations. The measurements in normal cerebrum of healthy volunteers revealed the following results of metabolite signal intensity ratios: pH 7.04 (+/- 0.01), PCr/alpha-ATP 0.51 (+/- 0.03), P(i)/alpha-ATP 0.17 (+/-0.02), PCr/P(i) 2.09 (+/-0.12), PDE/alpha-ATP 3.65 (+/-0.13) and PME/alpha-ATP 0.41 (+/-0.04). Meningiomas showed the most obvious changes when compared with normal brain tissue. They are characterized by an alkaline environment (pH 7.16 +/- 0.03; p<0.005), a decrease in the phosphocreatine peak (p<0.0001) and significantly decreased phosphodiesters (p<0.0001). Glioblastomas also showed alkalization (pH 7.12 +/- 0.02; p<0.001) and a decrease in PDE/alpha-NTP (p<0.05), but no significant changes in PCr/alpha-NTP or PCr/Pi. In gliomas with low malignancy, less distinct changes could be detected with slight alkalization (pH 7.09 +/- 0.02; p<0.05) and more than a two-fold reduction in the PDE/alpha-NTP ratio (p<0.05). The spectra of brain tumours during chemo- and radiotherapy indicated clear but inconsistent influence of the therapy.


Morphometric electron-microscopic investigation of the neuronal processes in the neurohypophysis in water-loaded, normal and water-deprived rats.
The neuronal processes in the neurohypophysis of the rat were analyzed by electron microscopy and morphometry after the secretion of antidiuretic hormone had been fully suppressed by water load. The water was supplied through a catheter inserted in the external jugular vein for 1.5, 2.5 and 24 h, respectively. The neurohypophysis was also examined in normal rats and rats that had been water-deprived for 72 h. The rats were fixed through chronically implanted catheters, so that at the time of fixation the animal was uninfluenced by anaesthesia and surgery. Water load increased the density of the neurosecretory granules in the endings in the zone nearest the basal lamina of the pericapillary space. The interpretation of this is that water load fills up the readily releasable pool of the neurosecretory granules. Water-deprival increased the density of dispersed microvesicles in the endings, especially in the zone near the basal lamina, and it is suggested that the dispersed microvesicles are involved in membrane recapture.


A systematic review of oil tanker truck disasters: Identifying prevention targets.
Oil tanker truck disasters have been reported worldwide; however, the circumstances, causes, and health effects of these disasters have not been described. To address this gap, we performed a systematic review using PRISMA criteria to better understand this public health problem and identify prevention targets. The academic and lay literatures were systematically searched for terms related to oil tanker truck disasters. Reports about civilian oil tanker truck disasters that occurred from 1997-2017 were included. Details about the disasters were summarized, including circumstances, identifiable causes, and health effects. The search yielded 4713 Nexis Uni articles, 199 Google results, and one PubMed article; 951 records met inclusion criteria, describing 224 oil tanker truck explosions or fires. At least 2909 people died as a result of these disasters, and 3038 additional people were hospitalized. Almost all deaths (94%) occurred in low- and low-middle-income countries (LMIC). This may largely be due to scooping - the practice of collecting spilled oil from disabled tanker trucks for use or resale. Using the Haddon matrix, potential targets for future disaster prevention were identified. These data highlight the circumstances, causes, and health burden related to oil tanker truck disasters. Most began as collisions or rollovers, but nearly half of the fatalities involved scooping. The findings suggest opportunities to promote road safety, improve scene safety and security protocols used by drivers and first responders, and promote public understanding of the dangers of scooping to prevent mass casualty disasters from disabled tanker trucks, particularly in LMIC.


Comparison of healthspan-related indicators between adults with and without HIV infection aged 18-59 in the United States: a secondary analysis of NAHNES 1999-March 2020.
As persons with HIV (PWH) live longer they may experience a heightened burden of poor health. However, few studies have characterized the multi-dimentional health of PWH. Thus, we aimed to identify the extent and pattern of health disparities, both within HIV infection status and across age (or sex) specific groups. We used cross-sectional data from the US National Health and Nutrition Examination Survey, 1999-March 2020. The adjusted prevalence of six healthspan-related indicators-physical frailty, activities of daily living (ADL) disability, mobility disability, depression, multimorbidity, and all-cause death-was evaluated. Logistic regression and Cox proportional hazards analyses were used to investigate associations between HIV status and healthspan-related indicators, with adjustment for individual-level demographic characteristics and risk behaviors. The analytic sample consisted of 33 200 adults (170 (0.51%) were PWH) aged 18-59 years in the United States. The mean (interquartile range) age was 35.1 (25.0-44.0) years, and 49.4% were male. PWH had higher adjusted prevalences for all of the 6 healthspan-related indicators, as compared to those without HIV, ranged from 17.4% (95% CI: 17.4%, 17.5%) vs. 2.7% (95%CI: 2.7%, 2.7%) for all-cause mortality, to 84.3% (95% CI: 84.0%, 84.5%) vs. 69.8% (95%CI: 69.7%, 69.8%) for mobility disability. While the prevalence difference was largest in ADL disability (23.4% (95% CI: 23.2%, 23.7%); P < 0.001), and least in multimorbidity (6.9% (95% CI: 6.8%, 7.0%); P < 0.001). Generally, the differences in prevalence by HIV status were greater in 50-59 years group than those in 18-29 group. Males with HIV suffered higher prevalence of depression and multimorbidity, while females with HIV were more vulnerable to functional limitation and disabilities. HIV infection was associated with higher odds for 3 of the 6 healthspan-related indicators after fully adjusted, such as physical frailty and depression. Sensitivity analyses did not change the health differences between adults with and without HIV infection. In a large sample of U.S. community-dwelling adults, by identifying the extent and pattern of health disparities, we characterized the multi-dimentional health of PWHs, providing important public health implications for public policy that aims to improve health of persons with HIV and further reduce these disparities.


Atrazine is not readily mineralised in 24 temperate soils regardless of pre-exposure to triazine herbicides.
Mineralisation of atrazine in soil has been shown to depend on previous exposure of the herbicide. In this study, 24 Danish soils were collected and screened for potential to mineralise atrazine. Six soils were chosen, because they had never been exposed to atrazine, whereas 18 soils were chosen because of their history of application of atrazine or the related compound terbuthylazine. None of the 24 soils revealed a mineralisation potential of more than 4% of the added atrazine within a 60 day timeframe. In an atrazine adapted French soil, we found 60% mineralisation of atrazine in 30 days. Cattle manure was applied in order to boost the microbial activity, and a 2-3% increase in the atrazine mineralisation was found in some of the temperate soils, while in the highly adapted French soil it caused a 5% reduction.


Ruptured renal artery aneurysm in pregnancy. Case report.
A patient who survived rupture of a renal artery aneurysm in pregnancy is described. The aneurysm was caused by fibromuscular dysplasia of the renal artery.


Tailgut cyst initially misdiagnosed as ovarian tumor.
Tailgut cyst (retrorectal cystic hamartoma) is an uncommon congenital lesion that arises from remnants of the embryonic post-anal gut. It is usually benign and located in the retrorectal/presacral space. A 45-year-old woman presented with lower abdominal discomfort, urinary frequency and right-sided pelvic mass. Digital rectal examination and computerized tomography scan demonstrated a multicystic complex mass occupying the region of the right ovary and extending into the retrorectal/presacral space. The initial diagnosis was neoplasm of the right ovary. At laparotomy, the mass was lying free from apparently normal internal genital organs. Excision of the mass from the right pelvis and retrorectal/presacral space and total abdominal hysterectomy were performed. Microscopic examination revealed that the wall of the cystic mass consists of a lining epithelium composed of columnar and squamous epithelium and a stroma composed of fibrous tissue containing scattered discontinuous bundles of smooth muscle fibers. Based on these histological findings, the final diagnosis was tailgut cyst. Tailgut cyst is an uncommon entity that should be included in the differential diagnosis of retrorectal/presacral mass. The treatment of choice is complete surgical excision.


DNA and oestradiol receptor distribution in human breast cancer.
The content of DNA and oestradiol receptors was measured in two different samples taken from the same tumoral mass of 33 primary infiltrating ductal carcinomas. The results were related to the total cytoplasmic protein and to the DNA of the tissue. The results showed that variations of both DNA and oestradiol receptors are frequent and often significant. The reliability of analyses carried out on a single biopsy is discussed.


Closing the Implementation Gap Comment on "Insights Gained From a Re-analysis of Five Improvement Cases in Healthcare Integrating System Dynamics Into Action Research".
Holmström et al provide an interesting and thought-provoking contribution to a perennial problem: why, despite a vast number of applications of simulation modelling in healthcare over the past 70 years, there is still remarkably little evidence of successful implementation of model results. Their paper is a retrospective analysis of five case studies, all undertaken as consultancy, that used a blend of system dynamics (SD) modelling and action research (AR). This commentary assesses the effectiveness of this approach in achieving implementation, based on the evidence presented, and discusses some of the issues raised. These issues include a comparison of Holmström's approach with group model building (GMB) in SD, the differences between healthcare modelling projects undertaken by (a) business consultants and (b) academics, and the challenges of undertaking 'systematic' reviews of the grey literature.


Preliminary in vitro and in vivo evaluation of specific activity of branched oligohexamethyleneguanidine hydrochloride.
Branched oligohexamethyleneguanidine hydrochloride (OHMG) possesses great potential for the development of novel drugs for the treatment of diseases caused by bacteria. This study aimed at evaluating the antimicrobial activity of OHMG against potential causative agents of oral and pharyngeal mucosa infections, specifically, the activity against 56 clinical strains, 5 of which were antibiotics-resistant. Also, a preliminary in vivo study of the specific activity of OHMG based on a traumatic stomatitis and gingivitis model in rabbits was carried out. In vitro antimicrobial activity of OHMG was determined by testing the minimal inhibitory concentration (MIC). OHMG displayed excellent activity against Streptococcus pneumoniae, Streptococcus pyogenes (MIC was 0.002-0.25 µg/ml), Moraxella catarrhalis (0.03-0.06 µg/ml), Neisseria gonorrhoeae (0.125-2 µg/ml). Almost complete healing of defects in the groups of animals within the 7-day application of 'OHMG hydrochloride' at concentrations of 0.1% and 0.3% after the thermal formation of the stomatitis and gingivitis model was observed.


Erythropoiesis-stimulating agents in anaemia due to chronic kidney disease: a cost-minimization analysis.
Some publications have shown that equivalent doses of erythropoiesis-stimulating agents (ESA) defined on label differ from those effective in clinical practice. Therefore, real costs could vary from theoretical costs in the treatment of anaemia in chronic kidney disease (CKD). To perform a cost-minimization analysis to establish the economic impact of the principal ESAs used in treating anaemia secondary to CKD in daily practice. to determine patient-month cost based on the erythropoietin resistance index (ERI); to analyze the difference in cost between pre-dialysis and peritoneal dialysis (PD) patients; and to analyze the association between iron deposits and ESA cost. This study was carried out at 2 tertiary hospitals in Spain. A multicentre cost-minimization analysis was performed in adult outpatients treated with ESAs for anaemia due to CKD. The primary outcome was the patient-month cost for each ESA. 409 patients were included. Median patient-month cost was: epoetin (103.2 [63.7, 187.8] euros), darbepoetin α (134.4 [67.2, 216.0] euros) and CERA (147.5 [98.3, 196.7] euros). Median patient-month cost according to ERI was: epoetin (1.60 [0.90, 2.60] euros/kg), darbepoetin α (2.01 [0.95, 3.48] euros/kg) and CERA (1.87 [1.33, 3.00] euros/kg). Median patient-month cost in pre-dialysis was 126.0 (73.7, 201.6) euros and in PD 153.0 (100.2, 275.4) euros. Median patient-month cost for patients with TSI < 20% was 147.5 (98.3, 224.9) euros compared to 100.9 (67.2, 196.7) euros which was the cost for patients with IST ≥ 20%. The median patient-month cost for patients with ferritin < 100 mcg/l was 134.4 (85.0, 201.6) euros compared to 100.8 (68.8, 196.7) euros, which was the cost for patients with ferritin ≥ 100 mcg/l (p = 0.242). Doses of CERA used in clinical practice are lower than those recommended on label, which directly influences cost and treatment efficiency. Cost stratification based on iron deposits has shown that patients with low TSI or ferritin require higher doses and consequently an associated higher cost. Thus, to guarantee adequate iron levels is essential in the rational use of ESAs.


Evaluation of sensory function after median nerve decompression in carpal tunnel syndrome using the current perception threshold test.
The recovery level for sensory function after carpal tunnel release for the treatment of idiopathic carpal tunnel syndrome (CTS) was assessed with the current perception threshold (CPT) test. Seventeen CTS patients (21 hands) were followed, and the CPTs at the index finger of each patient was measured preoperatively and at 1, 3, and 6 months postoperatively. After carpal tunnel release, there was significant recovery of CPT at all stimulation frequencies, indicating improvement of all sensory functions including sensations of temperature, pain, touch, and vibration.


Cellular expression of idiotopes defined by monoclonal antibodies.
Monoclonal anti-idiotype (Id) antibodies with specificities for determinants related to the antigen-binding sites of 3 BALB/c myeloma proteins, MOPC-460, HOPC-8 and J558, were used to study Id expression on murine lymphocytes. The monoclonal antibodies were shown to react only with Id structures associated with immunoglobulin on B cells. None of these 3 Id nor a VH Id, detected by a monoclonal antibody made against HOPC-8 heavy chain, were found on T cells. These Id were detected on splenic B cells in neonatal mice; the frequencies in normal, nude and germ-free mice were similar: MOPC-460 Id+: 1.05 +/- 1.7/10(4) spleen cells, HOPC-8 Id+: 1.45 +/- 1.2/10(4) and J558: 0.35 +/- 0.6/10(4). Almost all Id+ cells bore surface IgM, a few expressed surface IgG. MOPC-460 Id+ IgG+ cells were mainly gamma 2a+ or gamma 2b+, whereas J558 and HOPC-8 Id+ IgG+ cells were gamma 3+.


Identifying the electricity-saving driving behaviors of electric bus based on trip-level electricity consumption: a machine learning approach.
Electric buses (EBs) are gaining popularity worldwide as a more sustainable and eco-friendly alternative to diesel buses (DBs). Electricity-saving driving plays a crucial role in minimizing an EB's energy consumption, subsequently leading to an extended driving range. This study proposes a machine learning-based framework for identifying electricity-saving EB driving behaviors during various driving stages, including running on road segments, entering bus stops/intersections, and exiting bus stops/intersections. The proposed random forest (RF) model effectively evaluates the energy consumption level using EB drivers' historical driving data under different scenarios. Specifically, the electricity consumption factor (ECF), as the evaluation index, is divided into three categories to determine the implicit relationship between driving behavior and energy consumption. The results indicate that the classification accuracy of RF models surpasses 90%, which highlights the effectiveness in accurately identifying energy-efficient EB driving behaviors. In addition, the Shapley additive explanations (SHAP) and partial dependency plots (PDPs) are utilized to visualize and interpret the results of RF models. A speed interval of 30-40 km/h is identified as the most energy-efficient range for EB running on a road segment. Findings from this study can be applied to targeted optimization of electricity-saving driving strategies in different driving scenarios to improve the overall efficiency and sustainability of the transportation system.


Response factors in delay discounting: evidence for Pavlovian influences on delay discounting in pigeons.
Pigeons completed a delay-discounting task where in different conditions the required response was either key pecking or treadle pressing. Because of stimulus-reinforcer relations that are known to form between localized visual cues and the delivery of food (e.g., autoshaping), we predicted that there would be steeper rates of discounting with key pecking than treadle pressing. To account for possible effort differences between key pecking and treadle pressing, pigeons also completed a discounting task where multiple key pecks were required to gain access to the food. The rates of discounting for the key peck and effort-equivalence discounting procedures were similar, and both were steeper than the rate of discounting for the treadle-pressing procedure. While it is tacitly assumed that behavior in choice situations is largely under the control of operant contingencies, the present results suggest that when developing animal analogs to study discounting in a discrete-trial choice procedure, the stimulus-reinforcer relations (Pavlovian conditioning) may need to be taken into consideration.


Quantitative analysis of VEGF-C mRNA of extrahepatic cholangiocarcinoma with real-time PCR using samples obtained during endoscopic retrograde cholangiopancreatography.
Vascular endothelial growth factor (VEGF)-C overexpression in extrahepatic cholangiocarcinoma (ECC) has been shown to be correlated with lymph node metastasis. The intensity of immunohistochemical staining of VEGF-C protein in surgical samples has been used as index of VEGF-C overexpression in previous studies. The aim of the study was to examine if VEGF-C overexpression in ECC could be preoperatively detected by using samples obtained during ERCP. Consecutive patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for biliary stricture during the study period were prospectively analyzed. VEGF-C mRNA was quantified by real-time PCR methods using endoscopic samples obtained during ERCP. The high intensity of immunohistochemical staining of VEGF-C protein in surgical samples was used for the reference standard of VEGF-C overexpression. The level of S100P mRNA which was a novel diagnostic marker of ECC was also quantified to evaluate whether the endoscopic samples contained ECC cells. Twenty-five patients were enrolled in this study. Eighteen patients were diagnosed as ECC and seven patients were diagnosed as benign biliary structure. Nine of eighteen patients with ECC, who showed positive S100P mRNA in endoscopic samples and received surgical resection, were finally analyzed. Receiver operating characteristics analysis yielded VEGF-C mRNA cut-off value of 3.85 for detection of VEGF-C overexpression, and the diagnostic performance of VEGF-C mRNA measurement in the endoscopic sample for VEGF-C overexpression reached sensitivity of 75.0%, specificity of 100%, and accuracy of 88.9%. The quantification of VEGF-C mRNA of ECC with real-time PCR using endoscopic samples was useful for preoperative detection of VEGF-C overexpression.


[Medical management of patients with stable coronary artery disease in France in 2004. Data from the Mutualité Sociale Agricole].
To describe the treatment of ambulatory patients with coronary artery disease, using information from the French farmers' insurance fund (Mutualité Sociale Agricole, MSA) database. Analysis of cardiovascular medications bought and reimbursed during the second quarter of 2004 for 16,694 patients affiliated with the MSA who were first diagnosed with coronary artery disease in 1998, 2001 or 2003. On average, 71% of patients received antiplatelet agents, 56% beta-blockers, 59% statins, and 36% ACE inhibitors. Only 32% received the combination of antiplatelet agents, statins, and beta-blockers, and only 14% all four classes. Practice guidelines were followed more closely in patients diagnosed most recently. Patients receiving all four classes of secondary prevention medication more often has a history of myocardial infarction or were younger. Average doses were consistent with recommendations for beta-blockers, but appeared too low for ACE inhibitors and statins (except for atorvastatin). Medical management of patients with chronic coronary artery disease in France, while still suboptimal, is improving. Our findings, which are concordant with previous registry data, emphasize the underuse of recognized secondary prevention medications in very elderly patients and the importance of the initial prescription at diagnosis.


[Radiotherapy in nasopharyngeal cancer. Evaluation of 37 cases].
37 cases of nasopharyngeal tumors were studied which have been treated from January 1971 through December 1976 at the University Clinic for Radiotherapy and Radiobiology Vienna. These cases were analysed according to local and regional control and survival time. The 5-year-disease-free survival rate for all patients studied is 46%. Local and regional recurrences are discussed.


Hurricane Katrina and the Gulf oil spill: lessons learned.
Education and training about immediate responses are important for all mental health providers of immediate and continuing services to assist children, adolescents, adults, and families in the aftermath of disasters. To sensitively help with evacuations and return to normalcy, responders must also be trained to understand the culture and traditions of affected communities. It is important to provide knowledge about available resources and to emphasize the need for routines and self-care for both victims and responders in an environment that, with recovery, will reflect a new normal.


Process design for augmentation and spectrofluorometric quantification of neutral lipid by judicious doping of pathway intermediate in the culture of marine Chlorella variabilis for biodiesel application.
Over the past few years microalgae have emerged as the most promising feedstock for biodiesel production. However, enhancing lipid content remains a major scientific challenge. Many studies irrationally rely upon nitrogen starvation for improving lipid content at the cost of biomass. In this study, strategic enhancement of neutral lipid without compromising with biomass production was achieved in marine Chlorella variabilis by supplementing the culture with triacylglycerol pathway intermediate, citric acid (1 g L(-1) pure and 0.5 g L(-1) orange peel extract as a low cost substitute). The microalga accumulated 17% and 34% (on dry cell weight basis) more neutral lipid, when cultivated in with citric acid and orange peel extract as supplements respectively, without any adverse effect on growth. The medium supplemented with orange peel extract stimulated better growth than that supplemented with citric acid. Gas chromatography studies validated that both the supplemented media yielded desired fatty acid composition for biodiesel production.


Hypoxia induces expression and activation of AMPK in rat dental pulp cells.
AMP-activated protein kinase (AMPK) is a stress-responsive enzyme involved in cell adaptation to an energy crisis. We hypothesized that hypoxia suppresses oxidative phosphorylation and ATP production, resulting in AMPK activation to protect cells. We investigated the effects of hypoxia on cell proliferation, the expression of AMPK and hypoxia-inducible factor 1alpha (HIF-1alpha), the activation of AMPK, and the relationship between AMPK and HIF-1alpha expression in rat dental pulp RPC-C2A cells. AMPK in the cells was composed of catalytic alpha1, and regulatory beta1 and gamma1 subunit isoforms. Cell proliferation was initially suppressed under hypoxia, but it increased thereafter, together with an increase in the expression of AMPK and HIF-1alpha, and the activation of AMPK. Down-regulation of AMPKalpha1 by siRNA inhibited cell proliferation under both normoxia and hypoxia, revealing that AMPK induction and activation were required for cell proliferation, although HIF-1alpha expression under hypoxia was not affected.


Devitrification of ionomer glass and its effect on the in vitro biocompatibility of glass-ionomer cements.
The effects of devitrification of an ionomer glass with a molar composition 4.5SiO(2).3Al(2)O(3).1.5P(2)O(5).3CaO.2CaF(2) on cement formation and in vitro biocompatibility were investigated. Differential thermal analysis was used to study the phase evolution in the glass, and to determine the heat treatments for production of glass-ceramics. X-ray diffraction patterns from glass frit heat-treated at 750 degrees C for 2h contained peaks corresponding to apatite (JCPDS 15-876), whereas for samples heat-treated at 950 degrees C for 2h apatite and mullite (JCPDS 15-776) were the major phases detected. Transmission electron microscopy (TEM) confirmed that apatite and apatite-mullite phases were present after heat treatments at 750 degrees C and 950 degrees C respectively. Glass and glass-ceramics were ground to prepare <45microm powders and glass ionomer cements were produced using a ratio of 1g powder: 0.2g PAA: 0.3g 10% m/v tartaric acid solution in water. In vitro biocompatibility was evaluated using cultured rat osteosarcoma (ROS) cells. Scanning electron microscopy (SEM) showed that cells colonised the surfaces of cements prepared using untreated ionomer glass and glass crystallised to form apatite (750 degrees C/2h). However, quantitative evaluation using MTT and total protein assays indicated that more cell growth occurred in the presence of cements prepared using ionomer glasses crystallised to apatite than cements prepared using untreated glass. The least cell growth and respiratory activity was observed on cements made with crystallised glass containing both apatite and mullite. It was concluded that the controlled devitrification of ionomer glasses could be used to produce GIC bone cements with improved biocompatibility.


Reply to Nayak, P.K. Comment on "Samulewski et al. Magnetite Synthesis in the Presence of Cyanide or Thiocyanate under Prebiotic Chemistry Conditions. Life 2020, 10, 34".
We have considered the criticisms raised by Pranaba K. Nayak [...].


Genetic characterization of Cylindrospermopsis raciborskii (cyanobacteria) isolates from diverse geographic origins based on nifH and cpcBA-IGS nucleotide sequence analysis.
Isolates of the toxic, N(2)-fixing species Cylindrospermopsis raciborskii from various geographic locations were analyzed with respect to their genetic diversity based on the nifH and cpcBA-IGS genes. Gene sequences clustered according to their geographic origin, with the nifH sequences separating into European, Australian, and American groups and the cpcBA-IGS sequences separating into American and European or Australian groups. PCR primers for both genes were designed to exclusively amplify DNA from Cylindrospermopsis species, and an additional primer set for cpcBA-IGS was designed to specifically amplify the American C. raciborskii strains.


Biomarkers as predictors of treatment response to tricyclic antidepressants in major depressive disorder: A systematic review.
Tricyclic antidepressants (TCAs) are frequently prescribed in case of non-response to first-line antidepressants in Major Depressive Disorder (MDD). Treatment of MDD often entails a trial-and-error process of finding a suitable antidepressant and its appropriate dose. Nowadays, a shift is seen towards a more personalized treatment strategy in MDD to increase treatment efficacy. One of these strategies involves the use of biomarkers for the prediction of antidepressant treatment response. We aimed to summarize biomarkers for prediction of TCA specific (i.e. per agent, not for the TCA as a drug class) treatment response in unipolar nonpsychotic MDD. We performed a systematic search in PubMed and MEDLINE. After full-text screening, 36 papers were included. Seven genetic biomarkers were identified for nortriptyline treatment response. For desipramine, we identified two biomarkers; one genetic and one nongenetic. Three nongenetic biomarkers were identified for imipramine. None of these biomarkers were replicated. Quality assessment demonstrated that biomarker studies vary in endpoint definitions and frequently lack power calculations. None of the biomarkers can be confirmed as a predictor for TCA treatment response. Despite the necessity for TCA treatment optimization, biomarker studies reporting drug-specific results for TCAs are limited and adequate replication studies are lacking. Moreover, biomarker studies generally use small sample sizes. To move forward, larger cohorts, pooled data or biomarkers combined with other clinical characteristics should be used to improve predictive power.


Simultaneous determination of phenyl- and sulfonyl-urea herbicides in river water at sub-parts-per-billion level by on-line preconcentration and liquid chromatography-tandem mass spectrometry.
A method based on on-line preconcentration followed by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was developed for the determination of three sulfonyl-urea (thifensulfuron, metsulfuron, chlorsulfuron) and two phenyl-urea (isoproturon and chlortoluron) herbicides in water at sub-ppb concentration ranges. Preconcentration was accomplished using on-line enrichment on a C18 cartridge; the procedure was optimized by an evaluation of the breakthrough volumes for the target analytes. Subsequently, LC-ESI-MS/MS was adopted for analytes separation and detection. In particular, a selective reaction monitoring (SRM) approach, based on the detection of a peculiar fragment for each analyte, was chosen for MS/MS analysis, in order to enhance selectivity. Normalization to the response of a phenyl-urea herbicide (chloroxuron), used as an internal standard, was also adopted to achieve a reproducibility enhancement. The described method was applied to the analysis of the target analytes in river water samples and LOD values ranging between 8 and 30 ppt were obtained.


EIF4A3-mediated circ_0042881 activates the RAS pathway via miR-217/SOS1 axis to facilitate breast cancer progression.
Breast cancer (BC) is one of the most frequent cancer-related deaths in women worldwide. Studies have shown the potential impact of circRNAs in multiple human tumorigeneses. Research on the vital signaling pathways and therapeutic targets of circRNAs is indispensable. Here, we aimed to investigate the clinical implications and underlying mechanisms of circ_0042881 in BC. RT-qPCR validated circ_0042881 was notably elevated in BC tissues and plasma, and closely associated with BC clinicopathological features. Functionally, circ_0042881 significantly accelerated the proliferation, migration, and invasion of BC cells in vitro and tumor growth and metastasis in vivo. Mechanistically, circ_0042881 promoted BC progression by sponging miR-217 to relieve its inhibition effect in son of sevenless 1 (SOS1), which further activated RAS protein and initiated downstream signaling cascades, including MEK/ERK pathway and PI3K/AKT pathway. We also demonstrated that treatment of BAY-293, an inhibitor of SOS1 and RAS interaction, attenuated BC progression induced by circ_0042881 overexpression. Furthermore, Eukaryotic initiation factor 4A-III (EIF4A3) could facilitate circ_0042881 circularization. Altogether, we proposed a novel signaling network in which circ_0042881, induced by EIF4A3, influences the process of BC tumorigenesis and metastasis by miR-217/SOS1 axis.


Molecular cloning, functional characterization and localization of an annexin from a fish gill fluke Microcotyle sebastis (Platyhelminthes: Monogenea).
The full cDNA of an annexin gene from Microcotyle sebastis (MsANX) was cloned for the first time in monogeneans. The cDNA of MsANX comprises 1199bp with a 29bp 5' untranslated region, an open reading frame of 1062bp, and a 108bp 3' untranslated region. The recombinantly produced MsANX bound phosphatidylserine vesicles in the presence of Ca2+, whereas no MsANX was precipitated in the absence of free Ca2+. Phylogenetically, MsANX formed a cluster with human annexin A13, known as the earliest annexin in vertebrates and expressed mainly in the intestine. The localization of MsANX in M. sebastis was analyzed by Western blotting and immunohistochemistry using the antiserum raised against the recombinant MsANX. In Western blot analysis, rat antiserum bound to a protein corresponding to the MsANX in size when worm crude extracts were used as antigens, but no bands were detected by the antiserum when the excretory/secretory proteins of worms were used as antigens. In immunohistochemistry analysis, significant antibody binding annexin was found in the ovarian region, the pharynx and the intestinal caecum of the worm. Interestingly, the alimentary canal location of MsANX was similar to the location of human annexin A13, and further research is needed to trace evolutionary relationship among helminthic annexins and human annexin A13. Also it remains to be investigated whether immunization of naïve fish with the recombinant MsANX can induce protective immune responses against M. sebastis infection.


Pharmaceutical savings after gastric bypass surgery.
Clinically severe obesity (CSO) is a surgically treated disease. The Roux-en-Y gastric bypass (RYGBP) has been used to treat patients with CSO and has resulted in an improvement in co-morbidities. We speculated that after a period of weight loss, patients would require less medication, resulting in cost-savings to both the patient and the insurance company, as well as an overall gain in health. A retrospective study was performed which involved the first 100 patients who had undergone RYGBP at a community-teaching hospital. Analysis of the data was conducted by the Wilcoxon signed rank test. 64 patients met our inclusion criteria and had adequate follow-up data available. The mean BMI was 57 kg/m(2) (range 36.6- 85.4 kg/m(2)), the female to male ratio was 4:1 (51:13), and the mean age was 44 years (range 27-64). The average monthly medication expenditure was reduced from US dollars 317 (SEM 47.25, range US dollars 23.12-US dollars 1801.19) preoperatively, to US dollars 135 (SEM 35.35, range US dollars 0.00-US dollars 1122.72) postoperatively. This reduction is significant (P <0.01). Weight loss after RYGBP leads to a significant reduction in medication expenses. These medication savings offset the costs of the initial procedure and represent permanent financial savings for the patient and society.


alpha-Dicarbonyl compounds--key intermediates for the formation of carbohydrate-based melanoidins.
The Maillard reaction of carbohydrates and amino acids is the chemical basis for flavor and color formation in many processed foods. Dicarbonyl compounds, such as 1-, 3-deoxyosones and 1,4-dideoxyosones, as well as short-chain dicarbonyls, such as methylgyoxal or glyoxal, are key compounds of the Maillard browning reaction. The alpha-dicarbonyls are also starting materials for polymerization reactions which lead to formation of carbohydrate-based melanoidins. With regard to the dicarbonyl compound, different possible chemical structures of melanoidins will be discussed. The analysis by size-exclusion chromatography revealed that those colored compounds differ in their molecular size and are directly associated with reactions having specific alpha-dicarbonyl compounds.


Gut microbiome of mealworms (Tenebrio molitor Larvae) show similar responses to polystyrene and corn straw diets.
Some insects can degrade both natural and synthetic plastic polymers, their host and gut microbes play crucial roles in this process. However, there is still a scientific gap in understanding how the insect adapted to the polystyrene (PS) diet from natural feed. In this study, we analyzed diet consumption, gut microbiota responses, and metabolic pathways of Tenebrio molitor larvae exposed to PS and corn straw (CS). T. molitor larvae were incubated under controlled conditions (25 ± 1 °C, 75 ± 5% humidity) for 30 days by using PS foam with weight-, number-, and size-average molecular weight (Mw, Mn, and Mz) of 120.0, 73.2, and 150.7 kDa as a diet, respectively. The larvae exhibited lower PS consumption (32.5%) than CS (52.0%), and these diets had no adverse effects on their survival. The gut microbiota structures, metabolic pathways, and enzymatic profiles of PS- and CS-fed larvae showed similar responses. The gut microbiota of larvae analysis indicated Serratia sp., Staphylococcus sp., and Rhodococcus sp. were associated with both PS and CS diets. Metatranscriptomic analysis revealed that xenobiotics, aromatic compounds, and fatty acid degradation pathways were enriched in PS- and CS-fed groups; laccase-like multicopper oxidases, cytochrome P450, monooxygenase, superoxidase, and dehydrogenase were involved in lignin and PS degradation. Furthermore, the upregulated gene lac640 in both PS- and CS-fed groups was overexpressed in E. coli and exhibited PS and lignin degradation ability. The high similarity of gut microbiomes adapted to biodegradation of PS and CS indicated the plastics-degrading ability of the T. molitor larvae originated through an ancient mechanism that degrades the natural lignocellulose. Video Abstract.


Genomic amplification of the Gret1 retroelement in white-fruited accessions of wild vitis and interspecific hybrids.
Retrotransposons are retrovirus-related mobile sequences that have the potential to replicate via RNA intermediates and increase the genome size by insertion into new sites. The retroelement, Gret1, has been identified as playing a key role in generating fruit color variation in cultivated grape (Vitis vinifera L.) due to its insertion into the promoter of VvMybA1. Fruit color variation is an important distinguishing feature of cultivated grapes and virtually no fruit color variation is observed in wild grape species. The presence and relative copy number of Gret1 was assessed using quantitative PCR on 22 different Vitis species, only four of which (plus interspecific hybrids) are known to contain white accessions. Gret1 copy number was observed to vary by species as well as by color within species and was significantly higher in white-fruited accessions across all taxa tested. Additionally, genomic regions surrounding Gret1 insertion were sequenced in white V. vinifera, hybrid, V. labrusca, V. aestivalis, and V. riparia accessions.


Determination of porphyrins in urine by direct injection on a liquid chromatographic column coated with tributylphosphate.
To separate and quantify urinary porphyrins, acidified and centrifuged urine was injected on a reversed-phase high-performance liquid chromatographic column, LiChrosorb RP-18, coated with tributylphosphate. A linear pH gradient from pH 4.40 to pH 6.50 was applied in the eluent using phosphate buffers containing methanol (9:1). The method permits detection of uro- and coproporphyrin down to concentrations normally present in urine and also selective determination of the hepta-, hexa- and pentacarboxylic porphyrins present in urine from patients suffering from porphyria cutanea tarda.


Unraveling the behavior of oral drug products inside the human gastrointestinal tract using the aspiration technique: History, methodology and applications.
Fluid sampling from the gastrointestinal (GI) tract has been applied as a valuable tool to gain more insight into the fluids present in the human GI tract and to explore the dynamic interplay of drug release, dissolution, precipitation and absorption after drug product administration to healthy subjects. In the last twenty years, collaborative initiatives have led to a plethora of clinical aspiration studies that aimed to unravel the luminal drug behavior of an orally administered drug product. The obtained drug concentration-time profiles from different segments in the GI tract were a valuable source of information to optimize and/or validate predictive in vitro and in silico tools, frequently applied in the non-clinical stage of drug product development. Sampling techniques are presently not only being considered as a stand-alone technique but are also used in combination with other in vivo techniques (e.g., gastric motility recording, magnetic resonance imaging (MRI)). By doing so, various physiological variables can be mapped simultaneously and evaluated for their impact on luminal drug and formulation behavior. This comprehensive review aims to describe the history, challenges and opportunities of the aspiration technique with a specific focus on how this technique can unravel the luminal behavior of drug products inside the human GI tract by providing a summary of studies performed over the last 20 years. A section 'Best practices' on how to perform the studies and how to treat the aspirated samples is described. In the conclusion, we focus on future perspectives concerning this technique.