Obesity-Associated Metabolic Signatures Correlate to Clinical and Inflammatory Profiles of Asthma: A Pilot Study.
Obesity is associated with metabolic dysregulation, but the underlying metabolic signatures involving clinical and inflammatory profiles of obese asthma are largely unexplored. We aimed at identifying the metabolic signatures of obese asthma. Eligible subjects with obese (n = 11) and lean (n = 22) asthma underwent body composition and clinical assessment, sputum induction, and blood sampling. Sputum supernatant was assessed for interleukin (IL)-1β, -4, -5, -6, -13, and tumor necrosis factor (TNF)-α, and serum was detected for leptin, adiponectin and C-reactive protein. Untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolic profiles in sputum, serum and peripheral blood monocular cells (PBMCs) were analyzed by orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and pathway topology enrichment analysis. The differential metabolites were further validated by correlation analysis with body composition, and clinical and inflammatory profiles. Body composition, asthma control, and the levels of IL-1β, -4, -13, leptin and adiponectin in obese asthmatics were significantly different from those in lean asthmatics. OPLS-DA analysis revealed 28 differential metabolites that distinguished obese from lean asthmatic subjects. The validation analysis identified 18 potential metabolic signatures (11 in sputum, 4 in serum and 2 in PBMCs) of obese asthmatics. Pathway topology enrichment analysis revealed that cyanoamino acid metabolism, caffeine metabolism, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, pentose phosphate pathway in sputum, and glyoxylate and dicarboxylate metabolism, glycerolipid metabolism and pentose phosphate pathway in serum are suggested to be significant pathways related to obese asthma. GC-TOF-MS-based metabolomics indicates obese asthma is characterized by a metabolic profile different from lean asthma. The potential metabolic signatures indicated novel immune-metabolic mechanisms in obese asthma with providing more phenotypic and therapeutic implications, which needs further replication and validation.


Efficacy and safety of lixisenatide in a predominantly Asian population with type 2 diabetes insufficiently controlled with basal insulin: The GetGoal-L-C randomized trial.
To assess the effects on glycaemic control of lixisenatide vs placebo as add-on treatment to basal insulin (BI) ± metformin and effects on glycated haemoglobin (HbA1c) reduction in patients with insufficiently controlled type 2 diabetes (T2D). Patients (n = 448) with inadequately controlled T2D were randomized (1:1) to lixisenatide or placebo as add-on to BI ± metformin for 24 weeks after an 8-week run-in phase, during which BI was titrated to a target self-monitored plasma glucose (SMPG; 4.4-5.6 mmol/L). The primary endpoint was absolute change in HbA1c from baseline to week 24. Secondary efficacy endpoints included: percentage of responders; changes in 2-hour postprandial plasma glucose (PPG); 7-point SMPG (daily average); body weight (BW); total daily BI dose; fasting plasma glucose; and safety assessments. Baseline demographics were similar in the two treatment groups. After insulin optimization during run-in, lixisenatide was superior to placebo in mean change from baseline (7.9% [standard deviation {s.d.}, 0.66] and 7.9% [0.70], respectively) to week 24 in HbA1c (least squares mean [standard error {s.e.}] change -0.62% [0.09] vs -0.11% [0.09]; P < .0001, respectively) and higher proportions of patients achieved HbA1c targets. Two-hour PPG, daily mean SMPG and mean BW were reduced further and daily BI dose was lower with lixisenatide than placebo (-1.12 kg vs 0.04 kg [P < .0001]; -3.0 U vs -1.9 U [P = .0033], respectively). Treatment-emergent adverse events were greater with lixisenatide than placebo (63.8% vs 40.8%, respectively). The incidence of symptomatic hypoglycaemia was similar (lixisenatide 15.6% vs placebo 13.5%). In Asian patients insufficiently controlled on BI ± metformin, lixisenatide was superior to placebo in glycaemic control, with a tolerability profile in line with other glucagon-like peptide-1 receptor agonists. NCT01632163 (clinicaltrials.gov).


A Comprehensive Review of Mutations in the MERTK Proto-Oncogene.
Phagocytosis and elimination of shed aged photoreceptor outer segments (POS) by retinal pigment epithelial cells is crucial for photoreceptor function and survival. Genetic studies on a natural animal model of recessive retinal degeneration allowed the identification of MerTK, the gene encoding the surface receptor required for POS internalization. Following this discovery, screenings of DNA samples from patients have revealed that MERTK mutations cause retinal degenerations in humans. MERTK patients present some of the classical symptoms of retinitis pigmentosa, but it is atypical in that the disease develops very early during childhood and the macula is also involved early on. Therefore, the phenotype ought to be qualified as a rod-cone dystrophy. Recently, MERTK has been implicated in various types of cancers and sclerosis. This review identifies the different MERTK mutations known so far and describes associated pathologies.


Memory re-differentiation and reduced lymphocyte activation in chronic HCV-infected patients receiving direct-acting antivirals.
Recently, the treatment of HCV has advanced significantly due to the introduction of direct-acting antivirals (DAAs). Studies using interferon (IFN)-containing regimens failed to consistently show restoration of immunologic responses. Therefore, IFN-free DAA formulations provide a unique opportunity to dissect the immunologic effect of HCV cure. This study investigates the restoration of the immune compartment as a consequence of rapid viral clearance in patients successfully treated with DAAs and in the absence of IFN and ribavirin. Here, we evaluate the immunologic changes that occurred following DAA-mediated HCV cure. Peripheral blood from nineteen previously treatment-naïve patients with chronic HCV genotype 1a/1b who received an IFN and ribavirin-free regimen of daclatasvir, asunaprevir and BMS-791325 was evaluated. Immune reconstitution occurs in patients in whom HCV was successfully eradicated via DAA therapy. Restoration of the CD4(+) T-cell compartment in the peripheral blood and a re-differentiation of the T lymphocyte memory compartment resulted in a more effector memory cell population and a reduction in expression in the co-inhibitory molecule TIGIT in bulk T lymphocytes. Furthermore, we observed a partial reversal of the exhausted phenotype in HCV-specific CD8(+) T cells and a dampening of the activation state in peripheral NK cells. Collectively, our data provide the groundwork for dissecting the effect of DAA therapy on the immune system and identifying novel mechanisms by which chronic HCV infection exerts immunosuppressive effects on T cells through the recently described co-inhibitory molecule TIGIT.


The IkappaB kinase regulates chromatin structure during reconsolidation of conditioned fear memories.
Previously formed memories are susceptible to disruption immediately after recall due to a necessity to be reconsolidated after retrieval. Protein translation mechanisms have been widely implicated as being necessary for memory reconsolidation, but gene transcription mechanisms have been much less extensively studied in this context. We found that retrieval of contextual conditioned fear memories activates the NF-kappaB pathway to regulate histone H3 phosphorylation and acetylation at specific gene promoters in hippocampus, specifically via IKKalpha and not the NF-kappaB DNA-binding complex. Behaviorally, we found that inhibition of IKKalpha regulation of either chromatin structure or NF-kappaB DNA-binding complex activity leads to impairments in fear memory reconsolidation, and that elevating histone acetylation rescues this memory deficit in the face of IKK blockade. These data provide insights into IKK-regulated transcriptional mechanisms in hippocampus that are necessary for memory reconsolidation.


Need for Specialized Support Services for Nurse Victims of Physical Assault by Psychiatric Patients.
Assault of nurses in the psychiatric setting is an ongoing global concern. In a prior study by these authors, many nurses reported concern about the lack of supportive interventions offered to nurses after the assault event. These nurses reported ongoing psychosocial and emotional disturbance consistent with symptoms of post-traumatic stress disorder. A follow-up study was done to investigate the perceived need of assaulted nurses for specialized support groups to assist them in dealing with the experience. A quantitative, cross sectional survey descriptive research design was done to assess assaulted nurses' perceived need for specialized support groups. The survey also gathered data relating to the reporting of the assault. A qualitative narrative section was added to gather data that might have been missed in the quantitative segment. The sample consisted of 57 previously assaulted nurses currently working at multiple acute care sites. Study findings showed that if specialized support groups were available, 57% of the nurses might be interested in attending these, and 41% would be interested in attending these. These nurses also reported multiple signs and symptoms of post-traumatic stress disorder. Considering the serious negative impact of assault on nurses and their desire for follow-up support, there is a need for the availability of supportive services.


Using hospital at home to reduce admissions.
In the UK at present there is a constant pressure for inpatient beds; with this comes a need to develop services so that patients can be managed in their own homes. Although community nursing has historically been synonymous with district nursing, with the ageing population and the need to manage the increasing numbers of patients who have long-term conditions, community nursing is changing. This article describes a hospital in the home service, developed by one NHS trust; it not only delivers care traditionally provided in hospitals, but is also an effective setting for student nurses to undertake practice placements.


Applying Machine Learning Models to Predict Medication Nonadherence in Crohn's Disease Maintenance Therapy.
Medication adherence is crucial in the management of Crohn's disease (CD), and yet the adherence remains low. This study aimed to develop machine learning models that can help predict CD patients of nonadherence to azathioprine (AZA), and thus assist caregivers to streamline the intervention process. This single-centered, cross-sectional study recruited 446 CD patients who have been prescribed AZA between Sep 2005 and Sep 2018. Questionnaires of medication adherence, anxiety and depression, beliefs of medication necessity and concerns, and medication knowledge were provided to patients, while other data were extracted from the electronic medical records. Two machine learning models of back-propagation neural network (BPNN) and support vector machine (SVM) were developed and compared with logistic regression (LR), and assessed by accuracy, recall, precision, F1 score and the area under the receiver operating characteristic curve (AUC). The average classification accuracy and AUC of the three models were 81.6% and 0.896 for LR, 85.9% and 0.912 for BPNN, and 87.7% and 0.930 for SVM, respectively. Multivariate analysis identified four risk factors associated with AZA nonadherence: medication concern belief (OR=3.130, p<0.001), education (OR=2.199, p<0.001), anxiety (OR=1.549, p<0.001) and depression (OR=1.190, p<0.001), while medication necessity belief (OR=0.004, p<0.001) and medication knowledge (OR=0.805, p=0.013) were protective factors. We developed three machine learning models and proposed an SVM model with promising accuracy in the prediction of AZA nonadherence in Chinese CD patients. The study also reconfirmed that education, psychologic distress, and medication beliefs and knowledge are correlated to AZA nonadherence.


Comparison of five 2nd-generation supraglottic airway devices for airway management performed by novice military operators.
Five different second-generation supraglottic airway devices, ProSeal LMA, Supreme LMA, i-gel, SLIPA, and Laryngeal Tube Suction-D, were studied. Operators were inexperienced users with a military background, combat lifesavers, nurses, and physicians. This was a prospective, randomized, single-blinded study. Devices were inserted in the operating room in low light conditions after induction of general anesthesia. Primary outcome was successful insertion on the first attempt while secondary aims were insertion time, number of attempts, oropharyngeal seal pressure, ease of insertion, fibre optic position of device, efficacy of ventilation, and intraoperative trauma or regurgitation of gastric contents. In total, 505 patients were studied. First-attempt insertion success rate was higher in the Supreme LMA (96%), i-gel (87.9%), and ProSeal LMA (85.9%) groups than in the Laryngeal Tube Suction-D (80.6%) and SLIPA (69.4%) groups. Insertion time was shortest in the Supreme LMA (70.4 ± 32.5 s) and i-gel (74.4 ± 41.1 s) groups (p < 0.001). Oropharyngeal seal pressures were higher in the Laryngeal Tube Suction-D and ProSeal LMA groups than in other three devices. Most study parameters for the Supreme LMA and i-gel were found to be superior to the other three tested supraglottic airway devices when inserted by novice military operators.


Bacterial endotoxin: a trigger factor for alcoholic pancreatitis? Evidence from a novel, physiologically relevant animal model.
This study examined the possible role of endotoxinemia (from increased gut permeability) as an additional trigger factor for overt pancreatic disease and as a promoter of chronic pancreatic injury in alcoholics by using a rat model of chronic alcohol feeding and in vitro experiments with cultured pancreatic stellate cells (PSCs), the key mediators of pancreatic fibrosis. In the in vivo model, Sprague-Dawley rats fed isocaloric Lieber-DeCarli liquid diets +/- alcohol for 10 weeks were challenged with a single dose or 3 repeated doses of the endotoxin lipopolysaccharide (LPS) and the pancreas was examined. In the in vitro studies, rat PSCs were assessed for activation on exposure to LPS +/- ethanol. The expression of LPS receptors TLR4 and CD14 also was assessed in rat and human PSCs. In the in vivo model, single or repeated LPS challenge resulted in significantly greater pancreatic injury in alcohol-fed rats compared with rats fed the control diet without alcohol. Notably, repeated LPS injections caused pancreatic fibrosis in alcohol-fed rats, but not in rats fed the control diet. In the in vitro studies, PSCs were activated by LPS. Alcohol + LPS exerted a synergistic effect on PSC activation. Importantly, both rat and human PSCs expressed TLR4 and CD14. This study describes, for the first time, a clinically relevant animal model of alcohol-related pancreatic injury and provides strong in vivo and in vitro evidence that suggests that LPS is a trigger factor in the initiation and progression of alcoholic pancreatitis.


Where are we going? Beyond JNC 7.
On August 15, 2007, a panel discussion was held to discuss hypertension. The panel was moderated by Thomas D. Giles, MD, Tulane University School of Medicine, New Orleans, LA. Discussants included Suzanne Oparil, MD, University of Alabama at Birmingham, Birmingham, AL, and Thomas G. Pickering, MD, DPhil, Columbia Presbyterian Medical Center, New York, NY.


The type I collagen induction of MT1-MMP-mediated MMP-2 activation is repressed by alphaVbeta3 integrin in human breast cancer cells.
The influence of alphaVbeta3 integrin on MT1-MMP functionality was studied in human breast cancer cells of differing beta3 integrin status. Overexpression of beta3 integrin caused increased cell surface expression of alphaV integrin and increased cellular adhesion to extracellular matrix (ECM) substrates in BT-549, MDA-MB-231 and MCF-7 cells. beta3 integrin expression also enhanced the migration of breast cancer cells on ECM substrates and enhanced collagen gel contraction. In vivo, alphaVbeta3 cooperated with MT1-MMP to increase the growth of MCF-7 cells after orthotopic inoculation in immunocompromised mice, but had no influence on in vitro proliferation. Despite these stimulatory effects, overexpression of beta3 integrin suppressed the type I collagen (Col I) induced MMP-2 activation in all breast cancer cell lines analyzed. This was also evident in extracts from the MCF-7 tumors in vivo, where MMP-2 activation was stimulated by MT1-MMP transfection, but attenuated with beta3 integrin expression. Although our studies confirm important biological effects of alphaVbeta3 integrin on enhancing cell adhesion and migration, ECM remodeling and tumor growth, beta3 integrin caused reduced MMP-2 activation in response to Col I in vitro, which appears to be physiologically relevant, as it was also seen in tumor xenografts in vivo. The reduction of MMP-2 activation (and thus MT1-MMP activity) by alphaVbeta3 in response to Col I may be important in scenarios where cells which are activated for matrix degradation need to preserve some pericellular collagen, perhaps as a substrate for cell adhesion and migration, thus maintaining a balanced level of proteolysis required for efficient tumor growth.


Effects of dietary protein source on the digestive enzyme activities and electrolyte composition in the small intestinal fluid of chickens.
An experiment was conducted to investigate the effects of dietary protein source on the digestive enzymes and electrolyte composition of digesta fluid in the duodenum, jejunum, and ileum of chickens. A 2 × 3 factorial and completely randomized design that used 2 types of diets that differed only in their protein source [a corn-soybean meal-miscellaneous meal diet (CSMD) and a corn-miscellaneous meal diet (CMD)] and 3 types of cannulated roosters (duodenal, jejunal, and ileal cannulations) was adopted. The experiments included 5 replicates for each of the 6 treatments, and each replicate involved 3 cannulated chickens. The digesta samples were collected for 1 h every 4 h between 09:30 and 18:30 h on d 31, 33, and 35 of the experiment. The amylase, lipase, trypsin, and chymotrypsin activities and the electrolyte composition in the duodenal, jejunal, and ileal fluid were determined. In general, no significant differences between the 2 dietary groups were observed for the mean of duodenal, jejuna, and ileal amylase, trypsin, chymotrypsin, and lipase, respectively. However, the duodenal amylase activity was lower in the CMD group than the CSMD group (P < 0.05), which was probably related to the lower duodenal pH value that was observed in this group (P < 0.01). A higher jejunal Mg(2+) concentration was observed in chickens that were fed the CMD (P < 0.05), whereas the differences in the Na(+), K(+), Cl(-), and Ca(2+) concentrations in the small intestine were not significant between the 2 diets (P > 0.05). In conclusion, the digestive enzymes and electrolytes in the small intestinal fluid of chickens adapted to the protein source of the diet, and each segment of the small intestine displayed different modifications.


Synthesis of keratin proteins during maturation of cultured human keratinocytes.
We have examined the synthesis of keratin and total protein during cellular maturation in cultured oral and epidermal keratinocytes. Keratinocytes were separated on the basis of maturational age on gradients of Ficoll 400. Analysis of selected gradient fractions revealed that during maturation in culture the amount of protein/cell increases from 100 to 900 pg and the apparent rate of protein synthesis increases about two-fold. However, the proportion of protein that is keratin remains constant throughout this process. The major keratin proteins (58K, 56K, and 46K) are synthesized at the same relative rates throughout maturation in vitro. Therefore, during terminal differentiation in culture, the keratinocyte forms an expanding cell in which the rate of protein synthesis increases while the relative proportion of keratin proteins and nonkeratin proteins remain the same.


Visible Light-Driven Self-Powered Device Based on a Straddling Nano-Heterojunction and Bio-Application for the Quantitation of Exosomal RNA.
This paper reports the design and fabrication of a self-powered biosensing device based on TiO2 nanosilks (NSs)@MoS2 quantum dots (QDs) and demonstrates a bioapplication for the quantitative detection of exosomal RNA ( Homo sapiens HOXA distal transcript antisense RNA, HOTTIP). This self-powered device features enhanced power output compared to TiO2 NSs alone. This is attributed to the formation of a heterojunction structure with suitable band offset derived from the hybridization between TiO2 NSs and MoS2 QDs, i.e., the straddling (Type I) band alignment. The sensitization effect and excellent visible light absorption provided by MoS2 QDs can prolong interfacial carrier lifetime and improve energy conversion efficiency. This self-powered biosensing device has been successfully applied in quantitative HOTTIP detection through effective hybridization between a capture probe and HOTTIP. The successful capture of HOTTIP leads to a sequential decrease in power output, which is utilized for ultrasensitive quantitative HOTTIP detection, with a linear relationship of power output change versus the logarithm of HOTTIP concentration ranging from 5 fg/mL to 50 000 ng/mL and a detection limit as low as 5 fg/mL. This TiO2 NSs@MoS2 QDs-based nanomaterial has excellent potential for a superior self-powered device characterized by economical and portable self-powered biosensing. Moreover, this self-powered, visible-light-driven device shows promising applications for cancer biomarker quantitative detection.


Silicon: its ameliorative effect on plant defense against herbivory.
Plants protect themselves against pest attack utilizing both direct and indirect modes of defense. The direct mode of defense includes morphological, biochemical, and molecular barriers that affect feeding, growth, and survival of herbivores whereas the indirect mode of defense includes release of a blend of volatiles that attract natural enemies of the pests. Both of these strategies adopted by plants are reinforced if the plants are supplied with one of the most abundant metalloids, silicon (Si). Plants absorb Si as silicic acid (Si(OH)4) and accumulate it as phytoliths, which strengthens their physical defense. This deposition of Si in plant tissue is up-regulated upon pest attack. Further, Si deposited in the apoplast, suppresses pest effector molecules. Additionally, Si up-regulates the expression of defense-related genes and proteins and their activity and enhances the accumulation of secondary metabolites, boosting induced molecular and biochemical defenses. Moreover, Si plays a crucial role in phytohormone-mediated direct and indirect defense mechanisms. It is also involved in the reduction of harmful effects of oxidative stress resulting from herbivory by accelerating the scavenging process. Despite increasing evidence of its multiple roles in defense against pests, the practical implications of Si for crop protection have received less attention. Here, we highlight recent developments in Si-mediated improved plant resistance against pests and its significance for future use in crop improvement.


Ginsenoside Re protects methamphetamine-induced mitochondrial burdens and proapoptosis via genetic inhibition of protein kinase C δ in human neuroblastoma dopaminergic SH-SY5Y cell lines.
Recently, we have demonstrated that ginsenoside Re protects methamphetamine (MA)-induced dopaminergic toxicity in mice via genetic inhibition of PKCδ and attenuation of mitochondrial stress. In addition, we have reported that induction of mitochondrial glutathione peroxidase (GPx) is also important for neuroprotection mediated by ginsenoside Re. To extend our knowledge, we examined the effects of ginsenoside Re against MA toxicity in vitro condition using SH-SY5Y neuroblastoma cells. Treatment with ginsenoside Re resulted in significant attenuations against a decrease in the activity of GPx and an increase in the activity of superoxide dismutase (SOD) in the cytosolic and mitochondrial fraction. The changes in glutathione (GSH) paralleled those in GPx in the same experimental condition. Consistently, ginsenoside Re treatment exhibited significant protections against cytosolic and mitochondrial oxidative damage (i.e. lipid peroxidation and protein oxidation), mitochondrial translocation of PKCδ, mitochondrial dysfunction (mitochondrial transmembrane potential and intra-mitochondrial Ca(2+)), apoptotic events [i.e., cytochrome c release from mitochondria, cleavage of caspase-3 and poly(ADP-ribose)polymerase-1, nuclear condensation, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells], and a reduction in the tyrosine hydroxylase (TH) expression and TH activity induced by MA in SH-SY5Y neuroblastoma cells. These protective effects of ginsenoside Re were comparable to those of PKCδ antisense oligonucleotide (ASO). However, ginsenoside Re did not significantly provide additional protective effects mediated by genetic inhibition of PKCδ. Our results suggest that PKCδ is a specific target for ginsenoside Re-mediated protective activity against MA toxicity in SH-SY5Y neuroblastoma cells.


Combined Mcl-1 and YAP1/TAZ inhibition for treatment of metastatic uveal melanoma.
Uveal melanoma is the most common intraocular tumor in adults, representing approximately 5% of all melanoma cases. Up to 50% of uveal melanoma patients develop metastases that are resistant to most of the commonly used antineoplastic treatments. Virtually all uveal melanoma tumors harbor activating mutations in GNAQ or GNA11 , encoding Gαq and Gα11, respectively. Constant activity of these proteins causes deregulation of multiple downstream signaling pathways including PKC, MAPK and YAP1/TAZ. While the importance of YAP1 signaling for the proliferation of uveal melanoma has recently been demonstrated, much less is known about the paralog of YAP1 transcriptional coactivator, named TAZ; however, similar to YAP1, TAZ is expected to be a therapeutic target in uveal melanoma. We performed a small-scale drug screen to discover a compound synergistically inhibiting uveal melanoma proliferation/survival in combination with YAP1/TAZ inhibition. We found that the combination of genetic depletion of YAP1/TAZ together with Mcl-1 inhibition demonstrates a synergistic inhibitory effect on the viability of uveal melanoma cell lines. Similarly, indirect attenuation of the YAP1/TAZ signaling pathway with an inhibitor of the mevalonate pathway, that is, the geranyl-geranyl transferase inhibitor GGTI-298, synergizes with Mcl-1 inhibition. This combination could be potentially used as a treatment for metastatic uveal melanoma.


Demonstration of strong near-field radiative heat transfer between integrated nanostructures.
Near-field heat transfer recently attracted growing interest but was demonstrated experimentally only in macroscopic systems. However, several projected applications would be relevant mostly in integrated nanostructures. Here we demonstrate a platform for near-field heat transfer on-chip and show that it can be the dominant thermal transport mechanism between integrated nanostructures, overcoming background substrate conduction and the far-field limit (by factors 8 and 7, respectively). Our approach could enable the development of active thermal control devices such as thermal rectifiers and transistors.


Transfusional hemosiderosis and combined chelation therapy in sickle thalassemia.
Although the indications for transfusions in sickle cell syndromes are well listed, and chronic transfusion has become practicable since the recent advances in chelation therapy have essentially eliminated the risk of secondary iron overload, multi-transfused, non-compliant to long-term chelation therapy patients confront the complication of iron overload and secondary hemosiderosis. In thalassemia major patients, combined therapy with desferrioxamine and deferiprone has maximized tissue iron removal and may reduce the overall occurrence of hemosiderotic heart failure. Despite this, safety and contradictions of chelating agents are still controversial. The aim of this report is to present the results of this combination in a long-term transfused sickle beta-thalassemic patient suffering from severe heart failure and liver dysfunction.


RADIATION HAZARDS FROM CRITICALITY ACCIDENT IN OPEN POOL TYPE REACTOR.
In this study, a hypothetical nuclear criticality accident has occurred in open pool type reactor due to ejection of the control rod during loss of coolant accident. Dose rate distribution was determined for prompt neutrons and gamma rays resulting from first radiation pulse of the criticality accident. MCNP code has been used to determine the dose rate in different positions that the worker may locate inside the reactor during the accident. The results show that the maximum radiation dose is 2.52 Sv which located at the center of the top of the main pool. The worker located in the control room, the first floor and the ground floor will receive a dose of 68.2, 11.6 and 0.85 mSv, respectively. The worker located in the underground floor will receive a dose of 35 μSv. SKYDOSE and SKYNEUT codes were used to determine the dose distribution outside the reactor building resulting from skyshine effect where the shielding around the reactor core is sufficient to attenuate the radiation in the radial direction. MCNP code was used to verify the SKYDOSE and SKYNEUT results along the distance of 1200 m from the reactor. The results show that the person around the reactor would receive an accumulated dose ranged between 1776.7 and 0.02 μSv along the distance between 20 and 1200 m.


Initial conditions combine with sensory evidence to induce decision-related dynamics in premotor cortex.
We used a dynamical systems perspective to understand decision-related neural activity, a fundamentally unresolved problem. This perspective posits that time-varying neural activity is described by a state equation with an initial condition and evolves in time by combining at each time step, recurrent activity and inputs. We hypothesized various dynamical mechanisms of decisions, simulated them in models to derive predictions, and evaluated these predictions by examining firing rates of neurons in the dorsal premotor cortex (PMd) of monkeys performing a perceptual decision-making task. Prestimulus neural activity (i.e., the initial condition) predicted poststimulus neural trajectories, covaried with RT and the outcome of the previous trial, but not with choice. Poststimulus dynamics depended on both the sensory evidence and initial condition, with easier stimuli and fast initial conditions leading to the fastest choice-related dynamics. Together, these results suggest that initial conditions combine with sensory evidence to induce decision-related dynamics in PMd.


Anterior Chamber XEN Gel Stent Movements: The Impact on Corneal Endothelial Cell Density.
Although there are several examples of glaucoma drainage devices' dislocations in the literature, the movement of XEN gel stents is scarcely documented, and the impact of such displacements on the corneal endothelium remains unknown. In light of the recent global market withdrawal of the CyPass microstent over concerns with regard to endothelial cell loss, we present a case of XEN gel stent dislocation into the anterior chamber, with localized corneal damage. We describe the case of a 64-year-old female patient who underwent bilateral XEN gel stent implantation for normal-tension glaucoma. While right eye surgery was uneventful, intraocular pressure increased in the left eye, and examination revealed a flat filtration bleb with no microstent visible through the conjunctiva. A 3 mm segment of the XEN stent was visible within the anterior chamber, with corneal contact during eye movement and blinking. Endothelial cell density was measured twice 1 month apart before the XEN gel stent was replaced. First, our observations confirm that XEN gel stents can dislocate and advance within the anterior chamber. We speculate that this displacement was caused by regular eye rubbing after surgery. Second, this report illustrates that the position of a drainage device within the anterior chamber is dynamic and significantly influenced by eye movements and blinking. Finally, occasional corneal contact of a XEN gel stent can cause a reduction in endothelial cell density of 2.1% in a month, which represents 46.2% of the annual endothelial loss observed by Tan and colleagues in patients with a Baerveldt tube (4.54% annual decrease).


Avicenna (980-1037) on the Role of the Liver in Separating Fluid from the Blood, with Insight into the Process from E.H. Starling (1866-1907) a Millennium Later.
A statement was made by Avicenna (980-1037) in his Canon of Medicine that the liver separates fluid from the blood. An explanation for this view has not been considered. Since the statement emerged from an existing English translation of the Canon (which was made from a prior Latin edition), an alternative English translation of the first Hebrew edition was made in order to verify the statement and to seek additional insight, which could explain its basis, in fact. The English edition of Avicenna's Canon of Medicine published in 1932, translated from the Latin. First Hebrew edition of Avicenna's Canon of Medicine published in 1491, translated from the Arabic. None. The relevant sections of the Hebrew Canon on the origin of the body fluids were translated and compared with the existing English translation. The fluid generated by the liver is likely to be protein-containing, since it was described as frothy and suggests that it is lymph. The suggestion that the liver needs a watery fluid for its action cannot be explained. Ernest Henry Starling (1866-1907) measured lymph formation, showing it to be driven by physical forces. The liver stood out as being the organ with the largest capacity for lymph formation. The vascular walls within the liver were shown to have a higher permeability to serum proteins than any other source of lymph. Data are derived from Starling's publications based on individual experiments. These were not analyzed statistically. The explanation for Avicenna's statement that the liver separates moisture from the blood is most likely to be the discovery by Starling, a millennium later, that the liver is the major source of lymph production. The liver is a major source of lymph. Distortion of the architecture of the liver in cirrhosis and other chronic liver diseases lead to ascites, a condition of lymph overflow from the liver.


European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCC): Pancreatic Cancer.
European Cancer Organisation Essential Requirements for Quality Cancer Care (ERQCC) are written by experts representing all disciplines involved in cancer care in Europe. They give patients, health professionals, managers and policymakers a guide to essential care throughout the patient journey. Pancreatic cancer is an increasing cause of cancer mortality and has wide variation in treatment and care in Europe. It is a major healthcare burden and has complex diagnosis and treatment challenges. Care must be carried out only in pancreatic cancer units or centres that have a core multidisciplinary team (MDT) and an extended team of health professionals detailed here. Such units are far from universal in European countries. To meet European aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.


HETEROCHRONIC VARIATION IN THE DEVELOPMENTAL TIMING OF CRANIAL OSSIFICATIONS IN POECILIID FISHES (CYPRINODONTIFORMES).
The quantitative description of ossification sequences and other developmental events with respect to body size provides a basis for assessing the ontogenetic patterns underlying differences in morphological structure. To the extent that such sequences are evolutionarily conservative, they may also provide a basis for phylogenetic inference. Ossification profiles were examined in five species of poeciliid fishes of the genera Poecilia, Xiphophorus, and Poeciliopsis, selected to represent three lineages of varying evolutionary distinctiveness. Although ossification sequences are highly correlated among species, numerous small timing differences and reversals are evident, differences that are accentuated more among than within genera. The timing profiles by themselves, when used to construct hypothetical phylogenetic trees, contain sufficient historical information to recover evolutionary relationships consistent with conventional systematic criteria based primarily on adult osteology and external morphology. Character-state changes mapped onto the resulting trees can be interpreted directly as heterochronic accelerations and retardations of ossification.


Changing biosynthesis of terpenoid percursors in rice through synthetic biology.
Many highly valued chemicals in the pharmaceutical, biotechnological, cosmetic, and biomedical industries belong to the terpenoid family. Biosynthesis of these chemicals relies on polymerization of Isopentenyl di-phosphate (IPP) and/or dimethylallyl diphosphate (DMAPP) monomers, which plants synthesize using two alternative pathways: a cytosolic mevalonic acid (MVA) pathway and a plastidic methyleritritol-4-phosphate (MEP) pathway. As such, developing plants for use as a platform to use IPP/DMAPP and produce high value terpenoids is an important biotechnological goal. Still, IPP/DMAPP are the precursors to many plant developmental hormones. This creates severe challenges in redirecting IPP/DMAPP towards production of non-cognate plant metabolites. A potential solution to this problem is increasing the IPP/DMAPP production flux in planta. Here, we aimed at discovering, understanding, and predicting the effects of increasing IPP/DMAPP production in plants through modelling. We used synthetic biology to create rice lines containing an additional ectopic MVA biosynthetic pathway for producing IPP/DMAPP. The rice lines express three alternative versions of the additional MVA pathway in the plastid, in addition to the normal endogenous pathways. We collected data for changes in macroscopic and molecular phenotypes, gene expression, isoprenoid content, and hormone abundance in those lines. To integrate the molecular and macroscopic data and develop a more in depth understanding of the effects of engineering the exogenous pathway in the mutant rice lines, we developed and analyzed data-centric, line-specific, multilevel mathematical models. These models connect the effects of variations in hormones and gene expression to changes in macroscopic plant phenotype and metabolite concentrations within the MVA and MEP pathways of WT and mutant rice lines. Our models allow us to predict how an exogenous IPP/DMAPP biosynthetic pathway affects the flux of terpenoid precursors. We also quantify the long-term effect of plant hormones on the dynamic behavior of IPP/DMAPP biosynthetic pathways in seeds, and predict plant characteristics, such as plant height, leaf size, and chlorophyll content from molecular data. In addition, our models are a tool that can be used in the future to help in prioritizing re-engineering strategies for the exogenous pathway in order to achieve specific metabolic goals.


Dendrimer N-heterocyclic carbene complexes with rhodium(I) at the core.
Novel dendrimer N-heterocyclic carbene complexes with rhodium(I) located at the core were synthesized, and a positive dendrimer effect was found in the hydrosilylation of ketones catalyzed by them.


Catalysis of S-nitrosothiols formation by serum albumin: the mechanism and implication in vascular control.
Nitric oxide (NO(.)) is a short-lived physiological messenger. Its various biological activities can be preserved in a more stable form of S-nitrosothiols (RS-NO). Here we demonstrate that at physiological NO(.) concentrations, plasma albumin becomes saturated with NO(.) and accelerates formation of low-molecular-weight (LMW) RS-NO in vitro and in vivo. The mechanism involves micellar catalysis of NO(.) oxidation in the albumin hydrophobic core and specific transfer of NO(+) to LMW thiols. Albumin-mediated S-nitrosylation and its vasodilatory effect directly depend on the concentration of circulating LMW thiols. Results suggest that the hydrophobic phase formed by albumin serves as a major reservoir of NO(.) and its reactive oxides and controls the dynamics of NO(.)-dependant processes in the vasculature.


[A case of ammonium acid urate urinary stone].
We report a case of ammonium acid urate urinary stone. A 32-year-old woman with no past medical history presented with right back pain. The kidney-ureter-bladder X-ray and computed tomography revealed right ureteral and bilateral renal stones. The right ureteral stone was excreted spontaneously without treatment. The left renal stone was too large to be excreted and required extracorporeal shock-wave lithotripsy (ESWL). The analysis of the excreted stone revealed that it consisted of pure ammonium acid urate. Flakes of the left renal stone by ESWL were impacted in the left lower ureter and also rapidly grew in the left kidney. The right renal stone grew rapidly and right hydronephrosis developed due to the newly-formed right ureteral stone. As post-renal acute renal failure developed subsequently, ureteral stents were placed bilaterally. We finally treated the bilateral ureteral stone with transurethral ureterolithotripsy, the right renal stone with ESWL and the left renal stone with percutaneous nephrolithotripsy. During the course, dietary instruction was intervened for hyperuricemia. Although there were a few stones left after ESWL, they were halfway excreted without rapid growth of stones.


[Prevalence of neurological complications in Japanese patients with AIDS after the introduction of HAART].
We investigated trends in neurological complications of infection with human immunodeficiency virus (HIV) in Japan after the introduction of highly active antiretroviral therapy (HAART). Two questionnaire surveys were performed in hospitals treating acquired immunodeficiency syndrome (AIDS) to compare two periods: immediately after the introduction of HAART (1999-2001); and a few years later (2002-3). Neurological complications accompanied 15.9% in 1999-2001 and 9.8% in 2002-3. Neurological complications developed without HAART in about 80% of cases. Neurological complications developed as the first AIDS-defining disease for 8.3% of AIDS patients in 1999-2001 and for 5.4% in 2002-3. Prevalences of HIV encephalopathy and myelopathy decreased markedly over the study period, as reported in other developed nations. However, prevalences of cytomegalovirus encephalitis, PML and primary brain lymphoma did not decrease. PML and primary brain lymphoma occurred in patients who received HAART and whose CD4 counts were relatively high during the study period. This is probably related to the extended survival of HIV-infected individuals after the introduction of HAART as a worldwide therapy, and the reactivation of viremia or latent infection persisting within the central nervous system.


A Force on the Crown and Tug of War in the Periodontal Complex.
The load-bearing dentoalveolar fibrous joint is composed of biomechanically active periodontal ligament (PDL), bone, cementum, and the synergistic entheses of PDL-bone and PDL-cementum. Physiologic and pathologic loads on the dentoalveolar fibrous joint prompt natural shifts in strain gradients within mineralized and fibrous tissues and trigger a cascade of biochemical events within the widened and narrowed sites of the periodontal complex. This review highlights data from in situ biomechanical simulations that provide tooth movements relative to the alveolar socket. The methods and subsequent results provide a reasonable approximation of strain-regulated biochemical events resulting in mesial mineral formation and distal resorption events within microanatomical regions at the ligament-tethered/enthesial ends. These biochemical events, including expressions of biglycan, decorin, chondroitin sulfated neuroglial 2, osteopontin, and bone sialoprotein and localization of various hypertrophic progenitors, are observed at the alkaline phosphatase-positive widened site, resulting in mineral formation and osteoid/cementoid layers. On the narrowed side, tartrate-resistant acid phosphatase regions can lead to a sequence of clastic activities resulting in resorption pits in bone and cementum. These strain-regulated biochemical and subsequently biomineralization events in the load-bearing periodontal complex are critical for maintenance of the periodontal space and overall macroscale joint biomechanics.


Intraoperative Contrast-Enhanced Ultrasound in Colorectal Liver Metastasis Surgery Improves the Identification and Characterization of Nodules.
The sensitivity of preoperative assessment of colorectal liver metastases (CRLM) ranges from 74 to 80%. Intraoperative ultrasound (IOUS) associated with contrast-enhanced intraoperative ultrasound (CE-IOUS) may be able to improve this. Thus, the aims of this study were to assess the value of IOUS and CE-IOUS for the surgical approach and to determine risk factors both for the detection of new nodules and for the modification of the surgical strategy. Forty-three patients who underwent CRLM surgery were included. These patients had an MRI in the 8 weeks preceding surgery and benefited from intraoperative IOUS and CE-IOUS. The use of IOUS/CE-IOUS permitted the identification of 43 additional lesions and an improved characterization of nodules in 23 patients with a resulting modification of surgical strategy. Lesions were down-staged in six patients and up-staged in six patients. Chemotherapy (p = 0.02) and the presence of nodules in the left lobe (p = 0.04) were predictive factors for finding new nodules at IOUS/CE-IOUS. The discovery of a new nodule systematically modified surgical management. IOUS/CE-IOUS improved intraoperative management of liver metastases. The techniques enable pertinent modification of surgical resections and a reduction of residual lesions.


[Cervical fractures in autopsy records].
We reviewed the autopsy records of 1872 cases of death because of politrauma, gunshot wounds and suicidal hanging. The analysis included causes and frequency of cervical spine fractures, their most common localisation, architecture of bone destruction and their influence on cervical cord. The most common cause of cervical spine injury was motor vehicle accidents. We examined 82 specimens with traumatic fractures of cervical spine obtained from accident victims. About half of the injuries occurred in upper cervical spine. The most common fracture localisation was C2 with dens fracture as the most frequent injury. The most common spinal cord lesion was complete rupture mainly at the upper cervical spine level.


Typing of human enteroviruses by partial sequencing of VP1.
Human enteroviruses (family Picornaviridae) are the major cause of aseptic meningitis and also cause a wide range of other acute illnesses, including neonatal sepsis-like disease, acute flaccid paralysis, and acute hemorrhagic conjunctivitis. The neutralization assay is usually used for enterovirus typing, but it is labor-intensive and time-consuming and standardized antisera are in limited supply. We have developed a molecular typing system based on reverse transcription-PCR and nucleotide sequencing of the 3' half of the genomic region encoding VP1. The standard PCR primers amplify approximately 450 bp of VP1 for most known human enterovirus serotypes. The serotype of an "unknown" may be inferred by comparison of the partial VP1 sequence to those in a database containing VP1 sequences for the prototype strains of all 66 human enterovirus serotypes. Fifty-one clinical isolates of known serotypes from the years 1991 to 1998 were amplified and sequenced, and the antigenic and molecular typing results agreed for all isolates. With one exception, the nucleotide sequences of homologous strains were at least 75% identical to one another (>88% amino acid identity). Strains with homologous serotypes were easily discriminated from those with heterologous serotypes by using these criteria for identification. This method can greatly reduce the time required to type an enterovirus isolate and can be used to type isolates that are difficult or impossible to type with standard immunological reagents. The technique may also be useful for the rapid determination of whether viruses isolated during an outbreak are epidemiologically related.


The advertisement calls of two species of Brachycephalus (Anura: Brachycephalidae) from southern Atlantic Forest, Brazil.
The advertisement calls are known for only eight species within the genus Brachycephalus. Herein, we describe the advertisement calls of B. olivaceus and B. quiririensis, both species from southern Atlantic Forest, state of Santa Catarina, Brazil. The advertisement calls of these species are similar, composed by one short and high-frequency note. The parameters range overlap between calls, as exemplified by the dominant frequency of 6.4-7.0 kHz in B. olivaceus and 6.2-6.5 kHz in B. quiririensis. Additionally, we provide a compilation of the available bioacoustic information for this genus.


Factor structure of the CNS Vital Signs computerized cognitive battery in youth with neurological diagnoses.
Computerized cognitive batteries, such as CNS Vital Signs (CNSVS), can provide valuable information in clinical and research settings. However, psychometric properties, especially in children and adolescents, remain relatively understudied. The aim of this study was to investigate the factor structure of CNSVS in children and adolescents with neurological diagnoses. Participants with neurological diagnoses (N = 280) age 7-19 years were assessed as part of their clinical care at a tertiary hospital. All participants received the full CNSVS computerized cognitive battery, which contains seven subtests designed to measure attention, executive functioning, psychomotor speed, and memory. Principal components analyses were used to examine factor structure. Scores from CNSVS subtests loaded onto a three-component solution and accounted for 46% of the variance. The three components were deemed to best represent (1) speed, (2) memory, and (3) inhibition, with subtest scores loading differently than the original 11 primary and secondary domain scores would have suggested. Although the CNSVS program generates numerous primary and secondary domain scores, a three-component solution represents a more parsimonious approach to interpreting performance on the CNSVS in youth with neurological diagnoses. Confirmation of this factor solution in other samples is warranted.


Three distinct isoforms of ATP synthase subunit c are expressed in T. brucei and assembled into the mitochondrial ATP synthase complex.
One striking feature of the biology of trypanosomes is the changes in mitochondrial structure and function that occur as these parasites transition from one life cycle stage to another. Our laboratory has been interested in the role the mitochondrial ATP synthase plays in mitochondrial changes through the life cycle. Analysis of the recently completed T. brucei genome suggested that there may be multiple putative genes encoding ATP synthase subunit c. While homologous in their 3' ends, these genes differ in their 5' ends and, if expressed, would result in three distinct proteins. Our analysis showed that all three of the possible transcripts were detected in both procyclic and bloodstream stages, although the c-3 transcript was less abundant than that for c-1 or c-2. The three isoforms of subunit c are produced in both the bloodstream and procyclic stages and their mature protein products possess distinct N-terminal regions of the protein as found within mitochondria. All three isoforms are also incorporated into the assembled ATP synthase complex from procyclic cells. Although multiple subunit c genes have been found in other organisms, they produce identical polypeptides and the finding of significant differences in the mature proteins is unique to T. brucei.


[Geographical variation and the response to hydrothermal factor of stable carbon isotope (δ13C) in Pinus massoniana.]
We used 10 representative provenances at different latitudes in two 33-year-old Pinus massoniana provenance test stands (Chun'an Laoshan in Zhejiang and Taizi Mountain Shilong in Hubei) to measure the differences among provenances, study the geographical variation, and identify its responses to hydrothermal factors. The results showed that the δ13C of the average annual rings was significantly different among the provenances of P. massoniana, being higher in trees from high latitude than from low latitude. The δ13C of average annual rings showed a zonal variation trend, indicating an adaptation to the original environment. The δ13C of annual rings was negatively correlated with mean annual temperature (MAT), mean temperature in January (T1), annual precipitation (MAP), precipitation from May to September (P5-9) and cumulative temperature above 10 ℃ (CT). It was positively correlated with the aridity index (AI). The response function of AI toδδ13C annual rings in Chun'an and Taizi Mountain explained 37.5% and 42.5% of the variation, respectively, indicating that AI was the most important limiting factor. The Taizi Mountain test site in Hubei Province located in the central and western region with relatively dry soil and high aridity. Therefore, the δ13C of the average annual ring was 1.8% higher than that in the Chun'an test site. The δ13C rings of P. massoniana at the Taizi Mountain and Chun'an were sensitive to the temperature in July and August, respectively. Summer precipitation was the main factor for carbon isotope fractionation with stable rings. The sensitivity of different provenances to future climate changes was different.


Bone Mineral Density in Population Long-Term Exposed to Rare Earth Elements from a Mining Area of China.
This study aims to investigate the effects of individuals' exposure to rare earth elements (REEs) on bone metabolism. Adopting the inductively coupled plasma mass spectrometry, we measured REEs and eight other elements (Ca, Fe, Cu, Na, K, Zn, Mg, and P) in the hair of 53 miners exposed to REEs from Baiyunebo and 57 healthy farmers as the control group. Furthermore, bone mineral density (BMD) in both groups was assessed by dual-energy X-ray absorptiometry. Analysis of variance showed that the concentrations of La, Ce, Pr, Nd, Tb, Ho, Tm, and Yb in male hair of exposed group were significantly higher compared with the control group, whereas the concentrations of Ca and Fe in exposed group were significantly lower; the results of female hair, except for Ce, Tb, Ho, Tm, and Yb, were consistent with male hair. Student's t test showed that the BMD of exposed males at lumbar vertebrae, femoral neck, greater trochanter, and intertrochanter was significantly lower than that of controls, and exposed females reported lower BMD values at lumbar vertebrae and femoral neck. Multiple linear regression analysis showed that concentrations of differential REEs were inversely related to BMD in males, and concentrations of Ca and Fe were positively related to BMD both in males and females. Our study suggests that long-term environmental and occupational exposure leads to REE accumulation, and a low level of iron and calcium due to the competitive binding of REEs, which together induce bone metabolism disorders, and further reduce BMD.


Control of intracellular movement of connexins by E-cadherin in murine skin papilloma cells.
The gap junctional intercellular communication-deficient mouse skin papilloma cell line P3/22 expresses Cx43 but not E-cadherin. The E-cadherin gene-transfected cells (P3E1) communicate in a calcium-dependent manner and they were used to study how E-cadherin restores the function of connexins. At low calcium, Cx43 molecules remain in the cytoplasm of P3E1 cells and appear at cell-cell contact areas only in high-calcium medium. While Cx43 is unphosphorylated in P3E1 cells in low-calcium medium, two phosphorylated bands appeared at high calcium. However, when Cx26, which has no C-terminal tail that can undergo phosphorylation, was expressed in P3E1 cells, this connexin also moved to the plasma membrane after the calcium shift and partly colocalized with Cx43, suggesting that C-terminal phosphorylation is not essential for E-cadherin-mediated intracellular transport of connexins. In low calcium, both Cx26 and Cx43 remained and colocalized in the endoplasmic reticulum. As early as 30 min after the shift to high-calcium medium, both Cx43 and Cx26 began to accumulate in the Golgi apparatus. Intracellular movement of connexins to the cytoplasmic membrane at high calcium was effectively blocked by cytochalasin D and brefeldin A. These results suggest that E-cadherin junction formation at high calcium leads to formation of actin cables, which directly or indirectly transport connexins from the cytoplasm to the cell-cell contact membranes via the Golgi apparatus.


Somatic Embryogenesis in the Family Gentianaceae and Its Biotechnological Application.
The family Gentianaceae consists of 1736 species, which play an important role in human being existence due to their pharmacological and horticultural values. Many species accumulate bitter iridoid substances used medicinally and in flavorings, while others are cultivated because of beauty of their flowers showing a wide range of colors and patterns. Out of 99 genera belonging to the gentian family, process of somatic embryogenesis (SE) was reported for 5. The first reports, aimed at micropropagation of ornamental cultivars and production of secondary metabolites, concerned Centaurium erythraea Rafn., Eustoma russellianum Grieseb. and Exacum affine Balf. Somatic embryos were induced on different explants cultured in the liquid Murashige and Skoog medium supplemented with auxins and cytokinins. In the 1990s of the last century, significant progress in the exploration of the phenomenon of SE and its biotechnological application was made for the genus Gentiana. The process was induced on various explants and studied at the structural and ultrastructural levels. Regenerated plants were screened for genetic stability using flow cytometry, chromosome counting, and molecular markers. Besides typical indirect SE, the use of leaf fragments enabled to obtain single-cell origin of somatic embryos. On the other hand, proliferation of embryogenic callus in liquid medium resulted in the establishment of long-term embryogenic cell suspension cultures, paving the way not only to study the formation of somatic embryos and the development of regenerants but also to preserve the morphogenic potential of cell aggregates by cryopreservation. Cell suspensions re-established after storage in liquid nitrogen maintained their embryogenic character and allowed to obtain somatic embryo-derived regenerants that were true-to-type at both genetic and epigenetic levels. Another application of SE was related to genetic manipulation purposes. Efficient protocols of plant regeneration from callus-, cell suspension-, or leaf mesophyll-derived protoplasts allowed engaging procedures of somatic hybridization or protoplast electroporation for gentian genome modifications. Also, high embryogenic potential existing in the numerous gentian species enabled successful Agrobacterium-mediated transformation of G. cruciata L. and G. dahurica Fisch.


Impurity-stimulated heterogeneous nucleation of supercooled H2 clusters.
The sizes and mass spectra of large (N=1900-13,700 molecules) cold (approximately 3.1 K) H2 clusters have been measured after scattering from CO molecules. Cluster-size measurements after between 2 and 8 collisions indicate that 7% of the H2 molecules are evaporated. This loss agrees with calculations for the number of H2 molecules evaporated by the heat released in the transition from an initial liquid state to a final solid state. Even though heterogeneous nucleation is initiated after only a few collisions with CO molecules, the mass spectra show that additional captured CO molecules coagulate to form large CO clusters with up to n=11 molecules, suggesting that the outer layer is sufficiently liquidlike to facilitate mobility of the CO molecules. Since the calculated H2 cluster temperature (approximately 3.1 K) is below the superfluid transition temperature predicted for pH2 with density between 40% and 80% of the triple-point density, a shell-like region of low density near the cluster surface can be expected to be superfluid.


Lamination of pharmaceutical tablets due to air entrapment: direct visualization and influence of the compact thickness.
Capping and lamination are two problems that are often faced during the industrial manufacturing of pharmaceutical tablets. Several reasons have been proposed to explain these phenomena. Among them, air entrapment is supposed to play a role in some cases. Nevertheless, no direct proof were given to prove that air entrapment can promote lamination or capping and various publications have questioned this hypothesis. In this article, using a model product compacted on a compression simulator, a direct proof of the implication of air entrapment during lamination was given. In fact, at the surface of the compact, defects with a spherical shape, clearly linked with an entrapped bubble of air, began to appear on the surface of the compact just below the pressure level to which lamination was observed. Moreover it was also observed that, when the compact thickness increased, the lamination pressure decreased, meaning that the compact thickness can promote lamination. As a conclusion, contrary to what is said in some publications, air entrapment can be involved when problems of lamination occur, and, in this case, powder desaeration should be considered.


Bioactivites of two common polyphenolic compounds: Verbascoside and catechin.
Natural products can present remarkable biological and pharmacological activities. In traditional medicine, plants have been used historically in treating cancer, infections, and other inflammatory conditions. Verbascoside and catechin are widespread polyphenolic plant compounds that could play a role in the anti-inflammatory and health-promoting effects of plants and plant extracts. This study compares the potential cytotoxic effects of polyphenols verbascoside and catechin (6.25-200 µM) on human peripheral blood mononuclear cells (PBMC) for 48 h and myelomonocytic THP-1 and THP-1 Blue cells for 24 h. The effects of the compounds on immune activation markers such as indoleamine 2,3-dioxygenase (IDO) activity as well as on neopterin formation and nuclear factor-κB (NF-κB) activation were investigated. Cytotoxicity of the compounds was tested using Cell-Titer Blue assay. Verbascoside exhibited significant suppressive effects in mitogen-stimulated PBMC on tryptophan breakdown (>50 µM; IC50 value: 58.6 µM) and the production of neopterin (>6.25 µM; IC50 value: 217 µM). These effects correlated with a decline in cell viability, while THP-1 Blue cells were less sensitive. NF-κB activity was slightly enhanced at lower concentrations (<50 µM verbascoside) in stimulated cells and at the highest concentration used in unstimulated cells. Catechin had no relevant effects on cell viability and on the tested inflammation markers, except NF-κB activation in THP-1 Blue cells. The results obtained show that verbascoside and catechin represent effective compounds which interfere with immunobiochemical pathways that are highly relevant for immunosurveillance and competing virus infections.


Random Hyperboxes.
This article proposes a simple yet powerful ensemble classifier, called Random Hyperboxes, constructed from individual hyperbox-based classifiers trained on the random subsets of sample and feature spaces of the training set. We also show a generalization error bound of the proposed classifier based on the strength of the individual hyperbox-based classifiers as well as the correlation among them. The effectiveness of the proposed classifier is analyzed using a carefully selected illustrative example and compared empirically with other popular single and ensemble classifiers via 20 datasets using statistical testing methods. The experimental results confirmed that our proposed method outperformed other fuzzy min-max neural networks (FMNNs), popular learning algorithms, and is competitive with other ensemble methods. Finally, we identify the existing issues related to the generalization error bounds of the real datasets and inform the potential research directions.


Activating miRNA-mRNA network in gemcitabine-resistant pancreatic cancer cell associates with alteration of memory CD4+ T cells.
To identify key microRNAs (miRNAs) and their target mRNAs related to gemcitabine-resistant pancreatic cancer (PC) and investigate the association between gemcitabine-resistant-related miRNAs and mRNAs and immune infiltration. Expression profiles of miRNAs and mRNAs were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed miRNAs and mRNAs (referred to as "DEmiRNAs" and "DEmRNAs", respectively) were distinguished between gemcitabine-resistant PC cells and its parental cells. The DEmRNAs targeted by the DEmiRNAs were retrieved using miRDB, microT, and Targetscan. Furthermore, GO and KEGG pathway enrichment analysis and GSEA were performed. The Kaplan-Meier plotter was used to analyze the prognosis of key DEmiRNAs and DEmRNAs on PC patients. The relationship between the key DEmRNAs and tumor-infiltrating immune cells in PC was investigated using CIBERSORT method using the LM22 signature as reference. Key infiltrating immune cells were further analyzed for the associations with prognosis of TCGA PAAD patients. Four DEmiRNAs, including hsa-miR-3178, hsa-miR-485-3p, hsa-miR-574-5p, and hsa-miR-584-5p, were identified to target seven DEmRNAs, including MSI2, TEAD1, GNPDA1, RND3, PRKACB, TRIM68, and YKT6, individually, in gemcitabine-resistant PC cells versus parental cells. Gemcitabine-resistant PC cells were enriched in proteasome-related, immune-related, and memory CD4+ T cell-related pathways, indicating a gemcitabine therapeutic effect on PC cells. All four DEmiRNAs and almost all DEmRNAs had an impact on the prognosis of PC patients. All seven DEmRNAs had remarkable effects on CD4+ memory T cells, which were affected by the gemcitabine therapeutic effect. Effector memory CD4+ T cells rather than central memory CD4+ T cells predicted a good prognosis according to the TCGA PAAD dataset. Gemcitabine resistance can alter the fraction of memory CD4+ T cells via hsa-miR-3178, hsa-miR-485-3p, hsa-miR-574-5p and hsa-miR-584-5p targeted MSI2, TEAD1, GNPDA1, RND3, PRKACB, TRIM68, and YKT6 network in PC.


Altered expression of PTCH and HHIP in gastric cancer through their gene promoter methylation: novel targets for gastric cancer.
Human hedgehog-interacting protein (HHIP) and protein patched homolog (PTCH) are two negative regulators of the hedgehog signal, however, the mechanism of action in gastric cancer is unknown. Methylation of TSG promoters has been considered as a causative mechanism of tumorigenesis. In the present study, we first determined the expression of PTCH and HHIP mRNA and protein in gastric cancer tissues and adjacent normal tissues, and then detected methylation of the two genes to associate their expression and gene promoter methylation in gastric cancer. Expression in gastric cancer tissues and the cancer cells (AGS) were evaluated by reverse transcription-PCR (RT-PCR), qRT-PCR and IHC, while the methylation expression was valued by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP). Cell viability and apoptosis were analyzed by MTT assay and flow cytometry following treatment with 5-aza-dc. Results showed that PTCH and HHIP expression was reduced in gastric cancer tissues that were not associated with clinical features. Moreover, methylation of the promoters was reversely correlated with the expression. Following treatment with 5-aza-dc, AGS reduced cell viability and induced apoptosis, which is associated with upregulation of HHIP expression. The data demonstrated that loss of expression of HHIP and PTCH is associated with the methylation of gene promoters. In addition, 5-aza-dc-induced apoptosis correlated with the upregulation of HHIP expression in AGS. The findings demonstrated that the PTCH and HHIP genes may be novel targets for the control of gastric cancer.


Application of Third-generation Dual-source CT for Ultra-high Resolution Temporal Bone Imaging Using Automated Tube Voltage Adaptation in Children with Hearing Impairment.
Objective To evaluate the radiation dose and image quality of the third-generation dual-source CT using automated tube voltage adaptation (CARE kV) in temporal bone scanning in pediatric patients with hearing impairment. Methods Totally 27 children with hearing impairment less than 18 years old were randomly divided into two groups:Group A (n=14),examined with CARE kV (reference with 100 kV and 214 mA)and sinogram-affirmed iterative reconstruction;and Group B (n=13),examined with CARE kV (reference with 100 kV and 171 mA)and advanced modeled iterative reconstruction. The scan range was from eyebrow to the end of the mastoid process. CT values and image noise were measured.The signal to noise ratio (SNR)was calculated. Subjective image quality was assessed by two radiologists and later in a consensus reading. Results There was no significant difference in CT value,image noise,and SNR between these two groups (all P>0.05). Also,the subjective scores of the 10 anatomical structures showed no significant difference (all P>0.05). The CT dose index volume and dose-length product were (11.62+1.92)mGy and (106.92+37.48)mGy·cm,respectively,in group B and (21.28+2.19)mGy (t=12.15,P<0.001)and (229.65+56.26)mGy·cm (t=6.62,P<0.001)in group A,decreased by 45% and 53%. Conclusion Compared with the second-generation dual-source CT,the third-generation dual-source CT for the scanning of temporal bone with CARE kV can ensure image quality and reduce radiation dose.


Relationships between brachial artery flow mediated dilation and carotid artery intima-media thickness in patients with suspected coronary artery disease.
The correlation of peripheral endothelial dysfunction and intima-media thickness (IMT) in patients with suspected coronary artery disease (CAD) has been unclear. Inflammation and thrombosis may play a role at early stages of atherosclerosis. Thus, early atherosclerosis was noninvasively examined morphologically by IMT of carotid arteries, and functionally by flow mediated dilation (FMD) of brachial arteries in patients who were suspected of CAD and had undergone coronary angiography. Plasma antigen levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, representative atherogenic cytokines, tissue factor (TF) and tissue factor pathway inhibitor (TFPI), markers of coagulation, and plasma activity level of plasminogen activator inhibitor type-1 (PAI-1), a marker of defective fibrinolysis, were measured. Patients with coronary atherosclerosis in one or more vessels with lesion > or = 50% had significantly reduced FMD compared with those with angiographically normal coronary arteries. Carotid artery IMT increased significantly only in patients with advanced coronary atherosclerosis in one or more vessels with lesion > or = 90%. Plasma antigen levels of IL-6 were significantly increased in patients with reduced FMD (< 5%) compared to those in patients with FMD between 10 and 15%. Plasma antigen levels of TF, total and free TFPI, and PAI-1 activity tended to increase with a reduction in FMD. Thus, (1) FMD was reduced at early stages of CAD while IMT was increased in advanced CAD, and (2) inflammation and thrombosis may play a role in the early stages of the atherosclerotic process.


Post-COVID-19 syndrome: Insights into a novel post-infectious systemic disorder.
Coronavirus disease 2019 (COVID-19) is currently considered a complex systemic infectious and inflammatory disease, determined by the infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the cause of one of the most important epidemiological phenomena in the last century - the COVID-19 pandemic. This infectious-inflammatory disease may generate a wide range of clinical manifestations and biological modifications, explained by the ubiquitous nature of the SARS-CoV-2 receptors, represented by the angiotensin-converting enzyme-2 (ACE-2), and by the host's violent immune and proinflammatory reaction to the viral infection. These manifestations include immunological disturbances, which, according to certain clinical findings, may persist post-infection, in the form of a presumed systemic inflammatory entity, defined by several clinical concepts with a common pathological significance: post-COVID-19 multisystem (or systemic) inflammatory syndrome, post-COVID syndrome or long-COVID. Although the pathophysiological mechanisms of the post-COVID-19 syndrome are elusive at the present moment, there are currently several studies that describe a systemic inflammatory or autoimmune phenomenon following the remission of the COVID-19 infection in some patients, which suggests the existence of molecular and cellular immune abnormalities, most probably due to the host's initial violent immune response to the viral infection, in the form of three overlapping entities: secondary hemophagocytic lymph histiocytosis (HLH), macrophage activation syndrome (MAS) and cytokine release syndrome (CRS). Thus, this is reminiscent of different classic autoimmune diseases, in which various infections are risk factors in developing the autoimmune process.


Hydroxyethyl starch.
HES products should be designated by both their number average of molecular weight (that determines colloidal activity) and molar substitution ratios. In addition to the original HES-70/70 developed in 1960, a rapidly excreted HES-50/50 has been available since 1977. HES-70/70 and human albumin are equivalent in both healthy and hypoalbuminemia subjects in regard to maximal and total effects on plasma volume, intravascular colloidal activity and plasma concentration of ingested colloid. Albumin and HES-70/70 are extravasated at nearly equal rates. Albumin elimination is predominantly monoexponential. HES-70/70 however, is partly metabolized and partly excreted in urine at rates that decrease progressively as the amount remaining in the body decreases. HES-50/50 has maximal effects on plasma volume and colloidal activity similar to those of dextran-40, but it is eliminated twice as rapidly and unlike dextran-40, does not accumulate on repeated ingestion of large doses. HES ingestion increases apparent serum activity of alpha amylase by slowing enzyme elimination. Anaphylactoid reactions have been infrequent and mild, even on repetitive ingestion in recurrent "Phoresis" donors. The effect of HES on coagulation in urine but does not slow urine flow by hyperviscosity. Hydroxyethylation of waxy starches yields safe colloids with the advantage of permitting selective control of drug effects by altering independently molecular size and rate of enzymatic hydrolysis, tailoring drug kinetics to specific uses.


Gastrobronchial fistula repair followed by esophageal leak--rescue by transesophageal drainage of the pleural cavity.
A gastrobronchial fistula (GBF) associated with bilateral aspiration pneumonia was diagnosed six years after an esophagectomy with gastric pull-up. After failed surgical repair, an uncontained esophagopleural leak developed. Fistula closure was attempted by implanting a Wilson-Cook endoprosthesis, which quickly became dislodged. Transesophageal drainage was positioned endoscopically through the suture-line defect and led to closure of the leak after 10 days.


Feasibility and effect of in-home physical exercise training delivered via telehealth before bariatric surgery.
Optimal physical activity (PA) interventions are needed to increase PA in individuals with severe obesity, and optimize the results of bariatric surgery (BS). The aim of this study was to assess the feasibility and effect of Pre-Surgical Exercise Training (PreSET) delivered in-home via telehealth (TelePreSET) in subjects awaiting BS. Six women following the TelePreSET were compared to the women from a previous study (12 performing the PreSET in a gymnasium and 11 receiving usual care). In-home TelePreSET (12-weeks of endurance and strength training) was supervised twice weekly using videoconferencing. Physical fitness, quality of life, exercise beliefs, anthropometric measures and telehealth perception were assessed before and after 12-weeks. Satisfaction was evaluated with questionnaires at the end of the intervention. The TelePreSET participants attended 96% of the exercise sessions, and were very satisfied by the TelePreSET. The baseline telehealth perception score was high, and increased significantly after the intervention. The TelePreSET group significantly increased their physical fitness compared to the usual care group. No significant change was noted in other outcomes. The TelePreSET is feasible and seems effective to improve the physical fitness of women awaiting BS. Further studies are needed to confirm beneficial effects of this innovative mode of delivery.


Household and Individual Risk Factors for Cholera among Cholera Vaccine Recipients in Rural Haiti.
Oral cholera vaccination was used as part of cholera control in Haiti, but the vaccine does not provide complete protection. We conducted secondary data analyses of a vaccine effectiveness study in Haiti to evaluate risk factors for cholera among cholera vaccine recipients. Individuals vaccinated against cholera that presented with acute watery diarrhea and had a stool sample positive for Vibrio cholerae O1 were included as cases. Up to four vaccinated individuals who did not present for treatment of diarrhea were included as controls for each case, and matched by location of residence, enrollment time, and age. We evaluated sociodemographic characteristics and risk factors for cholera. Univariable and multivariable logistic regression were performed to identify risk factors for cholera among vaccinees. Thirty-three vaccine recipients with culture-confirmed cholera were included as cases. One-hundred-and-seventeen of their matched controls reported receiving vaccine and were included as controls. In a multivariable analysis, self-reporting use of branded household water disinfection products as a means of treating water (adjusted relative risk [aRR] = 44.3, 95% confidence interval [CI] = 4.19-468.05, P = 0.002), and reporting having a latrine as the main household toilet (aRR = 4.22, 95% CI = 1.23-14.43, P = 0.02), were independent risk factors for cholera. Self-reporting always treating water (aRR = 0.09, 95% CI = 0.01-0.57, P = 0.01) was associated with protection against cholera. The field effectiveness of water, sanitation, and hygiene interventions used in combination with cholera vaccination in cholera control should be measured and monitored over time to identify and remediate shortcomings, and ensure successful impact on disease control.


The carboxy-terminal serine 392 phosphorylation site of human p53 is not required for wild-type activities.
Wild-type p53 functions in the G1 DNA damage checkpoint pathway by activating gene transcription and preventing cell cycle progression. Others reported that mutation of the serine 386 codon in mouse p53 abolished its ability to suppress growth. Serine 386 of murine p53 and the homologous residue of human p53, serine 392, are phosphorylated in vivo and can be phosphorylated in vitro by casein kinase II (CKII). We constructed mutants that changed serine 392 of human p53 to alanine (p53-S392A) or aspartic acid (p53-S392D); cotransfection of both these mutants with a reporter gene carrying a p53-responsive element into the p53-null Saos-2 cell line activated transcription as well as did wild-type p53. Furthermore, both mutants blocked cell cycle progression after transient transfection in these cells. A stable derivative of the T98G human glioblastoma cell line was established that expressed p53-S392A in response to dexamethasone. Overexpression of this mutant activated transcription of the endogenous waf1 (also called cip1) and mdm2 genes to the same extent as wild-type p53 and also produced growth arrest. Finally, p53-S392A and p53-S392D suppressed foci formation by activated ras and adenovirus E1A oncogenes as efficiently as did wild-type p53. Thus, unlike mutants that altered the serine 15 phosphorylation site, elimination of the serine 392 phosphorylation site had no discernible effect on p53 function. We conclude that neither phosphorylation nor RNA attachment to serine 392 are required for human p53's ability to suppress cell growth or to activate transcription in vivo.


Cardiovascular and mortality benefits of sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus: CVD-Real Catalonia.
Evidence from prospective cardiovascular (CV) outcome trials in type 2 diabetes (T2DM) patients supports the use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) to reduce the risk of CV events. In this study, we compared the risk of several CV outcomes between new users of SGLT2i and other glucose-lowering drugs (oGLDs) in Catalonia, Spain. CVD-REAL Catalonia was a retrospective cohort study using real-world data routinely collected between 2013 and 2016. The cohorts of new users of SGLT2i and oGLDs were matched by propensity score on a 1:1 ratio. We compared the incidence rates and hazard ratio (HR) for all-cause death, hospitalization for heart failure, chronic kidney disease, and modified major adverse CV event (MACE; all-cause mortality, myocardial infarction, or stroke). After propensity score matching, 12,917 new users were included in each group. About 27% of users had a previous history of CV disease. In the SGLT2i group, the exposure time was 60% for dapagliflozin, 26% for empagliflozin and 14% for canagliflozin. The use of SGLT2i was associated with a lower risk of heart failure (HR: 0.59; 95% confidence interval [CI] 0.47-0.74; p < 0.001), all-cause death (HR = 0.41; 95% CI 0.31-0.54; p < 0.001), all-cause death or heart failure (HR = 0.55; 95% CI 0.47-0.63; p < 0.001), modified MACE (HR = 0.62; 95% CI 0.52-0.74; p < 0.001), and chronic kidney disease (HR = 0.66; 95% CI 0.54-0.80; p < 0.001). In this large, retrospective observational study of patients with T2DM from a Catalonia, initiation of SGLT-2i was associated with lower risk of mortality, as well as heart failure and CKD.


Formononetin Inhibits Progression of Endometriosis via Regulation of p27, pSTAT3, and Progesterone Receptor: In Vitro and In Vivo Studies.
Formononetin is one of the phytoestrogens that functions like a selective estrogen receptor modulator (SERM). In this study, we evaluated the effects of formononetin on endometriosis progression in vitro and in vivo. After pathological confirmation, 10 eutopic and ectopic endometria were collected from patients with endometriosis. Ten eutopic endometria samples were collected from patients who did not have endometriosis. To determine the cytotoxic dose and therapeutic dose of formononetin, the concentration of 70% of the cells that survived after formononetin administration was estimated using a Cell counting kit-8 (CCK 8) assay. Western blot analysis was used to determine the relative expression levels of BAX, p53, pAKT, ERK, pERK, p27, and pSTAT3 in the eutopic endometria without endometriosis, eutopic endometria with endometriosis, and ectopic endometria with endometriosis as the formononetin concentration was increased. We confirmed the effect of formononetin on apoptosis and migration in endometriosis using fluorescence-activated cell sorting (FACS) and wound healing assays, respectively. A mouse model of endometriosis was prepared using a non-surgical method, as previously described. The mice were intraperitoneally administered formononetin for four weeks after dividing them into control, low-dose formononetin (40 mg/kg/day) treatment, and high-dose (80 mg/kg/day) formononetin treatment groups. All the mice were euthanized after formononetin treatment. Endometriotic lesions were retrieved and confirmed using hematoxylin and eosin (H&E) staining. Immunohistochemical (IHC) staining of p27 was performed. We set the maximum concentration of formononetin administration to 80 μM through the CCK8 assay. Based on formononetin concentration, the expression levels of BAX, p53, pAKT, ERK, pERK, p27, and pSTAT3 proteins were measured using Western blot analysis (N = 4 per group). The expression level of pERK, p27, and pSTAT3 in eutopic endometrium with endometriosis tended to decrease with increasing formononetin concentration, and a significant decrease was noted at 80 μM. The expression of p27 in ectopic endometrium with endometriosis was also significantly decreased at 80 μM of formononetin. FACS analysis revealed that formononetin did not significantly affect apoptosis. In the wound healing assay, formononetin treatment revealed a more significant decrease in the proliferation of the eutopic endometrium in patients with endometriosis than in the eutopic endometrium without endometriosis. Relative expression of sex hormone receptors decreased with increasing formononetin doses. Although no significant differences were observed in the ER, PR-A, ERβ/ERα, and PR-B/PR-A, significant down-regulation of PR-B expression was noted after formononetin treatment at 80 μM. In the in vivo study, endometriotic lesions in the formononetin-treated group significantly decreased compared to those in the control group. The relative expression of p27 using IHC was highest in the control group and lowest in the high-dose formononetin treatment group. Formononetin treatment was shown to inhibit the proliferation of eutopic and ectopic endometria in patients with endometriosis through the regulation of p27, pSTAT3, and PR-B. In an endometriosis mouse model, formononetin treatment significantly reduced the number of endometriotic lesions with decreased p27 expression. The results of this study suggest that formononetin may be used as a non-hormonal treatment option for endometriosis.


REDOX RESPONSIVE TRANSCRIPTION FACTOR1 is involved in age-dependent and systemic stress signaling.
REDOX RESPONSIVE TRANSCRIPTION FACTOR1 (RRTF1) regulates redox homeostasis under stress, however the mechanism is mainly unknown. In a recent publication, we analyzed rrtf1 knockout (ko) and RRTF1 overexpressor lines of Arabidopsis thaliana and showed that RRTF1 plays a crucial role in reactive oxygen species (ROS) production. Ko line produces less and overexpressor lines constitutively high levels of ROS under stress, and the amount of ROS increases with increase in stress and the RRTF1 level in the plant. The transcription factor also activates systemic ROS signaling under stress. (1) In this report, we show that RRTF1 exerts different roles in young and old leaves. While RRTF1 enhances defense responses to high light (HL) stress in young leaves, it induces senescence and chlorosis in older leaves. These findings suggest that RRTF1 and/or RRTF1-mediated ROS signaling induce stress responses in an age-dependent manner, and the age-dependent alteration in the RRTF1 function might be important for plants' acclimation to the stress environment.


Highly thermoconductive polymer nanocomposite with a nanoporous alpha-alumina sheet.
A highly thermoconductive insulative polymer nanocomposite with a nanoporous alpha-alumina sheet was reported. The thermal conductivity of the nanocomposite along the surface normal was 12 W m(-1) K(-1) (41 vol % alumina), a value as high as that predicted theoretically for a nanocomposite with thermoconductive fillers that form a perfectly connected thermoconductive network. The high thermal conductivity is probably due to the continuous alpha-alumina phase that functions as an efficient phonon path in the nanocomposite. The results suggest that the structure of the filler is important for the design of highly thermoconductive materials.


[Synthesis, characterization and blood compatibility studies of waterproof breathable polyurethanes].
Adopting the two-step method and changing the proportion between PEG (Polyethylene glycol) and PTMG (poly (tetrahydrofuran), we used the MDI (4,4'-diphenylmethane diisocyanate) and short chain extender BDO (1,4-butanediol) as hard segment, the PTMG and PEG as soft segment, and hence prepared a series of polyether-based thermoplastic polyurethanes. FTIR showed the structure character of these polyurethanes. The determination of mechanics property and water contact angles revealed their good mechanics properties and hydrophilicity. Blood compatibility was evaluated by hemolysis test and platelet adhesion test, which revealed their good hemocompatibility. So those polyurethanes may be of wide application in the future.


Successive Interfacial Reaction-Directed Synthesis of CeO2@Au@CeO2-MnO2 Environmental Catalyst with Sandwich Hollow Structure.
Noble metal nanoparticle-based catalysts are widely used for the removal of hazardous materials. During the catalytic reactions, it is of particular importance for developing novel strategies to avoid the leaching or sintering of noble metal nanoparticles. Here, the 4-nitrophenol (4-NP) and CO, typical hazardous chemicals in industrial water and exhaust gases from vehicles, are studied for their removal using CeO2@Au@CeO2-MnO2 catalyst. The sandwich hollow structure is achieved by means of successive interfacial redox reaction without any surfactants and without involving any surface modifications. Because of the synergistic interaction between Au nanoparticles and oxides, the as-prepared environmental catalyst exhibits remarkable activity toward the 4-NP reduction. Moreover, the sandwich structure inhibits the growth of the Au nanoparticles and the as-prepared catalyst still displays high activity toward CO oxidation even when the catalyst is treated at 600 °C.


PEARS: A Web Tool for Fitting Time-Resolved Photoluminescence Decays of Perovskite Materials.
Time-resolved photoluminescence (TRPL) is a powerful tool to investigate charge carrier recombination processes in emissive materials. Perovskite materials are extremely promising for applications in solar cells; however, the interpretation of their TRPL is arduous due to the complicated nature of the recombination processes occurring in these materials. We present here the PErovskite cArrier Recombination Simulator (PEARS) web tool for effortlessly and quickly fitting TRPL of perovskite materials using advanced charge carrier recombination models, allowing for the extraction of recombination rate constants and trap state concentration. PEARS is flexible and can adapt to different situations, by ignoring recombination processes or fixing known parameters (e.g., the doping concentration). The tool is publicly available at https://pears-tool.herokuapp.com.


DCL2- and RDR6-dependent transitive silencing of SMXL4 and SMXL5 in Arabidopsis dcl4 mutants causes defective phloem transport and carbohydrate over-accumulation.
DICER-LIKE (DCL) enzymes process double-stranded RNA into small RNAs that act as regulators of gene expression. Arabidopsis DCL4 and DCL2 each allow the post-transcriptional gene silencing (PTGS) of viruses and transgenes, but primary PTGS-prone DCL4 outcompetes transitive PTGS-prone DCL2 in wild-type plants. This hierarchy likely prevents DCL2 having any detrimental effects on endogenous genes. Indeed, dcl4 mutants exhibit developmental defects and increased sensitivity to genotoxic stress. In this study, the mechanism underlying dcl4 defects was investigated using genetic, biochemical and high-throughput sequencing approaches. We show that the purple phenotype of dcl4 leaves correlates with carbohydrate over-accumulation and defective phloem transport, and depends on the activity of SUPPRESSOR OF GENE SILENCING 3, RNA-DEPENDENT RNA POLYMERASE 6 (RDR6) and DCL2. This phenotype correlates with the downregulation of two genes expressed in the apex and the vasculature, SMAX1-LIKE 4 (SMXL4) and SMXL5, and the accumulation of DCL2- and RDR6-dependent small interfering RNAs derived from these two genes. Supporting a causal effect, smxl4 smxl5 double mutants exhibit leaf pigmentation, enhanced starch accumulation and defective phloem transport, similar to dcl4 plants. Overall, this study elucidates the detrimental action of DCL2 when DCL4 is absent, and indicates that DCL4 outcompeting DCL2 in wild-type plants is crucial to prevent the degradation of endogenous transcripts by DCL2- and RDR6-dependent transitive PTGS.


Altered structures in the cytoplasm of the ependymal cells next to the periventricular nucleus of the turtle Mauremys caspica.
In the apical cytoplasm of some ependymal cells of the Hypothalamic Periventricular Nucleus of the turtle Mauremys caspica large amount of cell structures of difficult diagnose are found. Their morphology is variable seeming to correspond to cell organelles in a process of degeneration, characteristic feature of the high metabolic activity in the ventricular barrier. Their possible physiological significance is discussed in the present work.


Ultra-deep sequencing analysis of the hepatitis A virus 5'-untranslated region among cases of the same outbreak from a single source.
Hepatitis A virus (HAV) is a causative agent of acute viral hepatitis for which an effective vaccine has been developed. Here we describe ultra-deep pyrosequences (UDPSs) of HAV 5'-untranslated region (5'UTR) among cases of the same outbreak, which arose from a single source, associated with a revolving sushi bar. We determined the reference sequence from HAV-derived clone from an attendant by the Sanger method. Sixteen UDPSs from this outbreak and one from another sporadic case were compared with this reference. Nucleotide errors yielded a UDPS error rate of < 1%. This study confirmed that nucleotide substitutions of this region are transition mutations in outbreak cases, that insertion was observed only in non-severe cases, and that these nucleotide substitutions were different from those of the sporadic case. Analysis of UDPSs detected low-prevalence HAV variations in 5'UTR, but no specific mutations associated with severity in these outbreak cases. To our surprise, HAV strains in this outbreak conserved HAV IRES sequence even if we performed analysis of UDPSs. UDPS analysis of HAV 5'UTR gave us no association between the disease severity of hepatitis A and HAV 5'UTR substitutions. It might be more interesting to perform ultra-deep sequencing of full length HAV genome in order to reveal possible unknown genomic determinants associated with disease severity. Further studies will be needed.


Violent Injuries Among College Students in China: An Exploration of Gender Mental Stress Model.
The purpose of this study was to explore the gender-specific mental stress model of violent injuries among Chinese college students. A cross-sectional, multistage sampling process was employed to recruit a total of 5025 college students from 22 universities in China. Survey respondents reported their exposure to violent injuries and noted individual and environmental factors that could relate to violent injuries. Both unadjusted and adjusted statistical methods were used to examine the relationships between selected individual and environmental variables with violent injuries among male and female college students. The overall prevalence of violent injuries among male and female college students in this study was 4.40% (95% CI [0.10%, 7.80%]) and 5.20% (95% CI [0.05%, 10.35%]). The study found that higher mental stress (OR: 3.32), lower level universities (OR: 5.99), and family location in rural areas (OR: 4.00) were associated with a higher likelihood of violent injuries, and mothers employed as professionals (OR: 0.07) was associated with lower prevalence of violent injuries among male students. Unlike male students, mental stress and mothers' occupation were not associated with violent injuries among female students. University type was also associated with violent injuries but this association was inverted (OR: 0.06) among female students. This study found gender-specific relationships affecting violent injuries among college students in China. Prevention strategies need to be developed in consideration of gender influences and should be enacted to reduce the negative impact of violent injuries on society and personal health in China.


[Association of sleep problems with self-rated health - a large epidemiologic survey in the working population].
To investigate the association between various sleep problems and self-rated health (SRH), a total of 43,092 (34,164 men and 8,928 women) employees were surveyed by means of a self-administered questionnaire. The risk of suboptimal (poor, very poor) SRH associated with sleep problems was estimated using multivariable logistic regression with odds ratios (ORs) as measures of associations. Because the prevalence of suboptimal SRH differed by sex (men 29.4% and women 34.1%, P < 0.001), the analyses were done separately for men and women. Employees sleeping less than 6 hrs/day (OR = 1.39 for men, 1.40 for women), with difficulty initiating sleep (OR=4.44 for men, 3.85 for women), with difficulty maintaining sleep (OR=5.72 for men, 4.85 for women), with early morning awakening (OR=3.87 for men, 4.25 for women), with difficulty waking up in the morning (OR=3.30 for men, 3.40 for women), feeling tired when waking up in the morning (OR=4.97 for men, 4.82 for women), and excessive daytime sleepiness at work (OR=2.34 for men, 2.11 for women) had a significantly higher odds of suboptimal SRH compared to those without sleep problems. The association between sleep problems and suboptimal SRH did not differ between men and women. In conclusion, the data point to an independent relationship between sleep problems and suboptimal SRH among Japanese employees.