Molar excess of coordinating N-heterocyclic carbene ligands triggers kinetic digestion of gold nanocrystals.
There has been much interest in evaluating the strength of the coordination interactions between N-heterocyclic carbene (NHC) molecules and transition metal ions, nanocolloids and surfaces. We implement a top-down core digestion test of Au nanoparticles (AuNPs) triggered by incubation with a large molar excess of poly(ethylene glycol)-appended NHC molecules, where kinetic dislodging of surface atoms and formation of NHC-Au complexes progressively take place. We characterize the structure and chemical nature of the generated PEG-NHC-Au complexes using 1D and 2D 1H-13C NMR spectroscopy, supplemented with matrix assisted laser desorption/ionization mass spectrometry, and transmission electron microscopy. We further apply the same test using thiol-modified molecules and find that though etching can be measured the kinetics are substantially slower. We discuss our findings within the classic digestion of transition metal ores and colloids induced by interactions with sodium cyanide, which provides an insight into the strength of coordination between the strong σ-donating (soft Lewis base) NHC and Au surfaces (having a soft Lewis acid character), as compared to gold-to-gold covalent binding.


Altered gene expression in frontal cortex and midbrain of 3,4-methylenedioxymethamphetamine (MDMA) treated mice: differential regulation of GABA transporter subtypes.
Changes in gene expression were examined in the brain of mice treated with a drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, also called Ecstasy). Frontal cortex and midbrain mRNA, analyzed by differential display polymerase chain reaction (DD-PCR) method, showed an altered expression of several cDNAs, 11 of which were isolated, cloned and sequenced. The sequence of one MDMA-induced mRNA corresponds (99.3%) to the mouse gamma-amino butyric acid (GABA) transporter 1 (mGAT1). The established involvement of GABA neurotransmission in the activity of several abused drugs prompted us to focus herein on MDMA effect on the GABA transporter gene family. Semi-quantitative PCR analysis with primers selective to the reported mGAT1 sequence confirmed that MDMA treatment increased mGAT1 expression. Time-course study of the expression of the three GABA transporter subtypes showed that MDMA induced a differential temporal activation of mGAT1 and mGAT4, but had no effect on mGAT2. Quantitative real-time PCR further proved the increased expression of mGAT1 and mGAT4 upon MDMA treatment. Western immunoblotting with anti-GAT1 antibodies showed that MDMA also increased GAT1 protein levels, suggesting that neurotransmission of GABA was altered. MDMA effect was also verified in serotonin transporter knockout (-/-) mice that are insensitive behaviorally to MDMA; the drug did not increase GAT1 protein level in these mutants. In mice, tiagabine and NO-711, inhibitors of GABA transporters, restrained MDMA-induced acute toxicity and death. These results should facilitate novel approaches to prevent deleterious effects, including fatality, induced by MDMA and similar abused psychostimulants.


Impact of dietary fiber intake on glycemic control, cardiovascular risk factors and chronic kidney disease in Japanese patients with type 2 diabetes mellitus: the Fukuoka Diabetes Registry.
Dietary fiber is beneficial for the treatment of type 2 diabetes mellitus, although it is consumed differently in ethnic foods around the world. We investigated the association between dietary fiber intake and obesity, glycemic control, cardiovascular risk factors and chronic kidney disease in Japanese type 2 diabetic patients. A total of 4,399 patients were assessed for dietary fiber intake using a brief self-administered diet history questionnaire. The associations between dietary fiber intake and various cardiovascular risk factors were investigated cross-sectionally. Body mass index, fasting plasma glucose, HbA1c, triglyceride and high-sensitivity C-reactive protein negatively associated with dietary fiber intake after adjusting for age, sex, duration of diabetes, current smoking, current drinking, total energy intake, fat intake, saturated fatty acid intake, leisure-time physical activity and use of oral hypoglycemic agents or insulin. The homeostasis model assessment insulin sensitivity and HDL cholesterol positively associated with dietary fiber intake. Dietary fiber intake was associated with reduced prevalence of abdominal obesity, hypertension and metabolic syndrome after multivariate adjustments including obesity. Furthermore, dietary fiber intake was associated with lower prevalence of albuminuria, low estimated glomerular filtration rate and chronic kidney disease after multivariate adjustments including protein intake. Additional adjustments for obesity, hypertension or metabolic syndrome did not change these associations. We demonstrated that increased dietary fiber intake was associated with better glycemic control and more favorable cardiovascular disease risk factors including chronic kidney disease in Japanese type 2 diabetic patients. Diabetic patients should be encouraged to consume more dietary fiber in daily life.


AN9, a petunia glutathione S-transferase required for anthocyanin sequestration, is a flavonoid-binding protein.
AN9 is a glutathione S-transferase from petunia (Petunia hybrida) required for efficient anthocyanin export from the site of synthesis in the cytoplasm into permanent storage in the vacuole. For many xenobiotics it is well established that a covalent glutathione (GSH) tag mediates recognition of molecules destined for vacuolar sequestration by a tonoplast-localized ATP-binding cassette pump. Here we inquired whether AN9 catalyzes the formation of GSH conjugates with flavonoid substrates. Using high-performance liquid chromatography analysis of reaction mixtures containing enzyme, GSH, and flavonoids, including anthocyanins, we could detect neither conjugates nor a decrease in the free thiol concentration. These results suggest that no conjugate is formed in vitro. However, AN9 was shown to bind flavonoids using three assays: inhibition of the glutathione S-transferase activity of AN9 toward the common substrate 1-chloro 2,4-dinitrobenzene, equilibrium dialysis, and tryptophan quenching. We conclude that AN9 is a flavonoid-binding protein, and propose that in vivo it serves as a cytoplasmic flavonoid carrier protein.


[Innovation in research].
We briefly revise the economic resources that the State allocated between the years 2000 and 2005, and their relationship with the production of research projects. In face of the few fiscal resources, innovations are proposed to the traditional research model, sustained in producing new products. Assuming it is possible to perform innovations in the process of producing a service or a product, which implies modifying the regional and national policies, driving the model proposed by P. Drucker of producing innovations with technology with T in capital letters, would on turn generate patents and social and economic profitability.


Gamma-phase shifting in awake monkey visual cortex.
Gamma-band synchronization is abundant in nervous systems. Typically, the strength or precision of gamma-band synchronization is studied. However, the precise phase with which individual neurons are synchronized to the gamma-band rhythm might have interesting consequences for their impact on further processing and for spike timing-dependent plasticity. Therefore, we investigated whether the spike times of individual neurons shift systematically in the gamma cycle as a function of the neuronal activation strength. We found that stronger neuronal activation leads to spikes earlier in the gamma cycle, i.e., we observed gamma-phase shifting. Gamma-phase shifting occurred on very rapid timescales. It was particularly pronounced for periods in which gamma-band synchronization was relatively weak and for neurons that were only weakly coupled to the gamma rhythm. We suggest that gamma-phase shifting is brought about by an interplay between overall excitation and gamma-rhythmic synaptic input and has interesting consequences for neuronal coding, competition, and plasticity.


Treatment of Pseudomonas aeruginosa Biofilm Present in Endotracheal Tubes by Poly-l-Lysine.
The endotracheal tube (ETT) is an essential interface between the patient and ventilator in mechanically ventilated patients. However, a microbial biofilm is formed gradually on this tube and is associated with the development of ventilator-associated pneumonia. The bacteria present in the biofilm are more resistant to antibiotics, and current medical practices do not make it possible to eliminate. Pseudomonas aeruginosa is one of the leading pathogens that cause biofilm infections and ventilator-associated pneumonia. Poly-l-lysine (pLK) is a cationic polypeptide possessing antibacterial properties and mucolytic activity by compacting DNA. Here, we explored the antibiofilm activity of pLK to treat P. aeruginosa biofilms on ETTs while taking into consideration the necessary constraints for clinical translation in our experimental designs. First, we showed that pLK eradicates a P. aeruginosa biofilm formed in vitro on 96-well microplates. We further demonstrated that pLK alters bacterial membrane integrity, as revealed by scanning electron microscopy, and eventually eradicates biofilm formed either by reference or clinical strains of P. aeruginosa biofilms generated in vitro on ETTs. Second, we collected the ETT from patients with P. aeruginosa ventilator-associated pneumonia. We observed that a single dose of pLK is able to immediately disrupt the biofilm structure and kills more than 90% of bacteria present in the biofilm. Additionally, we did not observe any lung tolerance issue when the pLK solution was instilled into the ETT of ventilated pigs, an animal model particularly relevant to mimic invasive mechanical ventilation in humans. In conclusion, pLK appears as an innovative antibiofilm molecule, which could be applied in the ETT of mechanically ventilated patients.


Image-Based Remodeling.
Imagining what a proposed home remodel might look like without actually performing it is challenging. We present an image-based remodeling methodology that allows real-time photorealistic visualization during both the modeling and remodeling process of a home interior. Large-scale edits, like removing a wall or enlarging a window, are performed easily and in real time, with realistic results. Our interface supports the creation of concise, parameterized, and constrained geometry, as well as remodeling directly from within the photographs. Real-time texturing of modified geometry is made possible by precomputing view-dependent textures for all faces that are potentially visible to each original camera viewpoint, blending multiple viewpoints and hole-filling when necessary. The resulting textures are stored and accessed efficiently enabling intuitive real-time realistic visualization, modeling, and editing of the building interior.


Aromatase gene expression and regulation in the female rat pituitary.
Aromatase cytochrome P450, the key enzyme of estrogen biosynthesis from androgens, is encoded by CYP19. Its structure shows some peculiarities: exons II to X encode the protein, while multiple alternative exons I encode unique 5'-untranslated regions of the aromatase mRNA transcripts. Immunohistochemistry studies in the rat have shown that pituitary aromatase expression is sex-dependent and varies across the estrous cycle, suggesting that estrogens might be involved in the regulation of aromatase activity and might act locally as a paracrine or autocrine factor in the pituitary. In the present study, we used RT-PCR to characterize aromatase transcripts and real-time PCR to quantify the expression of the total aromatase mRNA at the different stages of the estrous cycle and from an ovariectomy and estradiol replacement model. We identified the two previously described aromatase transcripts with a specific 5'untranslated region of the brain 1f and the gonadal PII transcripts. Total aromatase mRNA expression in the pituitary varied significantly during the estrous cycle, with the highest level occurring on the day of metestrus. After ovariectomy, we observed an increase of aromatase mRNA levels, and this effect was completely prevented by estradiol administration. These results suggest that pituitary aromatase mRNA expression is downregulated by estrogens.


The relationship between characteristics of context and research utilization in a pediatric setting.
Research utilization investigators have called for more focused examination of the influence of context on research utilization behaviors. Yet, up until recently, lack of instrumentation to identify and quantify aspects of organizational context that are integral to research use has significantly hampered these efforts. The Alberta Context Tool (ACT) was developed to assess the relationships between organizational factors and research utilization by a variety of healthcare professional groups. The purpose of this paper is to present findings from a pilot study using the ACT to elicit pediatric and neonatal healthcare professionals' perceptions of the organizational context in which they work and their use of research to inform practice. Specifically, we report on the relationship between dimensions of context, founded on the Promoting Action on Research Implementation in Health Services (PARIHS) framework, and self-reported research use behavior. A cross-sectional survey approach was employed using a version of the ACT, modified specifically for pediatric settings. The survey was administered to nurses working in three pediatric units in Alberta, Canada. Scores for three dimensions of context (culture, leadership and evaluation) were used to categorize respondent data into one of four context groups (high, moderately high, moderately low and low). We then examined the relationships between nurses' self-reported research use and their perceived context. A 69% response rate was achieved. Statistically significant differences in nurses' perceptions of culture, leadership and evaluation, and self-reported conceptual research use were found across the three units. Differences in instrumental research use across the three groups of nurses by unit were not significant. Higher self-reported instrumental and conceptual research use by all nurses in the sample was associated with more positive perceptions of their context. Overall, the results of this study lend support to the view that more positive contexts are associated with higher reports of research use in practice. These findings have implications for organizational endeavors to promote evidence-informed practice and maximize the quality of care. Importantly, these findings can be used to guide the development of interventions to target modifiable characteristics of organizational context that are influential in shaping research use behavior.


Intercellular adhesion molecule 1 knockout abrogates radiation induced pulmonary inflammation.
Increased expression of intercellular adhesion molecule 1 (ICAM-1; CD54) is induced by exposure to ionizing radiation. The lung was used as a model to study the role of ICAM-1 in the pathogenesis of the radiation-induced inflammation-like response. ICAM-1 expression increased in the pulmonary microvascular endothelium and not in the endothelium of larger pulmonary vessels following treatment of mice with thoracic irradiation. To quantify radiation-induced ICAM-1 expression, we utilized fluorescence-activated cell sorting analysis of anti-ICAM-1 antibody labeling of pulmonary microvascular endothelial cells from human cadaver donors (HMVEC-L cells). Fluorochrome conjugates and UV microscopy were used to quantify the fluorescence intensity of ICAM in the irradiated lung. These studies showed a dose- and time-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium. Peak expression occurred at 24 h, while threshold dose was as low as 2 Gy. To determine whether ICAM-1 is required for inflammatory cell infiltration into the irradiated lung, the anti-ICAM-1 blocking antibody was administered by tail vein injection to mice following thoracic irradiation. Inflammatory cells were quantified by immunofluorescence for leukocyte common antigen (CD45). Mice treated with the anti-ICAM-1 blocking antibody showed attenuation of inflammatory cell infiltration into the lung in response to ionizing radiation exposure. To verify the requirement of ICAM-1 in the inflammation-like radiation response, we utilized the ICAM-1 knockout mouse. ICAM-1 was not expressed in the lungs of ICAM-1-deficient mice following treatment with thoracic irradiation. ICAM-1 knockout mice had no increase in the inflammatory cell infiltration into the lung in response to thoracic irradiation. These studies demonstrate a radiation dose-dependent increase in ICAM-1 expression in the pulmonary microvascular endothelium, and show that ICAM-1 is required for inflammatory cell infiltration into the irradiated lung.


Sensitive detection of a novel class of toluene-degrading denitrifiers, Azoarcus tolulyticus, with small-subunit rRNA primers and probes.
Azoarcus tolulyticus is a new class of widely distributed toluene-degrading denitrifiers of potential importance in remediating benzene, toluene, ethylbenzene, and xylene (BTEX)-contaminated environments. To detect these organisms in the environment, 16S rRNA gene-based phylogenetic probes were developed. Two sets of specific PCR amplification primers and two oligonucleotide hybridization probes were designed and tested against both closely and distantly related environmental isolates. All of these primers and probes were specific to the species A. tolulyticus. The sensitivity of the PCR amplification primer sets was evaluated with DNA isolated from A. tolulyticus Tol-4 pure culture and from sterile soils seeded with a known number of Tol-4 and Escherichia coli cells. These primer sets were able to detect 1 fg to 1 pg of template DNA from the pure culture and 1.11 x 10(2) to 1.1 x 10(8) Tol-4 cells per g of soil in the presence of 1.56 x 10(10) E. coli cells. These two PCR amplification primers were also successfully tested at two field sites. The primers identified the A. tolulyticus strains among the toluene-degrading bacteria isolated from a low-O2-high-NO(3)- aquifer at Moffett Field, Calif. Also, the presence of A. tolulyticus was detected in the groundwater samples from a BTEX-contaminated aquifer at an industrial site in Detroit, Mich., which showed anaerobic toluene degradation.


Echocardiographic and electrocardiographic presentations of patients with endomyocardial biopsy-proven cardiac amyloidosis.
Cardiac amyloidosis is under diagnosed and its prevalence is unknown. This is a retrospective, nonrandomised, single centre study of patients with endomyocardial biopsy-proven cardiac amyloidosis focusing on their echocardiographic and electrocardiogram (ECG) presentations. This is the first case series in Malaysia on this subject. We identified all of our endomyocardial biopsyproven cardiac amyloidosis patients from January 2010 to January 2018 and reviewed their medical records. All patients echocardiographic and ECG findings reviewed and analysed comparing to basic mean population value. In total there are 13 biopsy-proven cardiac amyloidosis patients. All of the biopsies shows light chain (AL) amyloid. Majority of the patients (8, 61.5%) is male, and most of our patients (8, 61.5%) is Chinese. All seven patients on whom we performed deformation imaging have apical sparing pattern on longitudinal strain echocardiogram. Mean ejection fraction is 49.3%, (SD=7.9). All patients have concentric left ventricular hypertrophy and right ventricular hypertrophy. Diastolic dysfunction was present in all of our patients with nine out of 13 patients (69.2%) having restrictive filling patterns (E/A ≥2.0 E/e' ≥15). On electrocardiogram, 12 (92%) patients have prolonged PR interval (median 200ms, IQR 76.50ms) and 9 (69.2%) patients have pseudoinfarct pattern. Echocardiography plays an important role in diagnosing cardiac amyloidosis. The findings of concentric left ventricular hypertrophy with preserved ejection fraction without increased in loading condition should alert the clinician towards its possibility. This is further supported by right ventricular hypertrophy and particularly longitudinal strain imaging showing apical sparing pattern.


Antibiotic utilisation in adult and children patients in Kosovo hospitals.
There are no reliable data on antibiotic use in Kosovo hospitals. The aim of this survey was to monitor volumes and patterns of antibiotic use in hospitalised patients in order to identify targets for quality improvement. Data on antimicrobial use were collected from seven hospitals in Kosovo during 2013 using the standardised point prevalence survey (PPS) methodology as developed by the ESAC (European Surveillance of Antimicrobial Consumption) and ARPEC (Antibiotic Resistance and Prescribing in European Children). The survey included all inpatients receiving an antimicrobial agent on the day of the PPS. Overall, 1667 patients were included in the study: adults 1345 (81%) and children 322 (19%). Of the hospital inpatients, 579/1345 (43%) adults and 188/322 (58%) children received at least one antibiotic during a hospital stay. The top three antibacterial subgroups (ATC level 3) were β-lactam antibiotics, cephalosporins and aminoglycosides. In all hospital centres, the most commonly prescribed antibiotic was ceftriaxone (39% for adult and 36% for children). Antibiotics were administered mainly parenterally in 74% of adults and 94% of children. Empirical prescribing was higher in adults 498/579 (86%) and children 181/188 (96%), compared with targeted treatment based on susceptibility testing-81 (14%) and 8 (4%), respectively. Antibiotic use in Kosovo's hospitals is very high. Gathered data will be an important tool to identify targets for quality improvement and will support preparation of guidelines and protocols for the prudent use of antibiotics.


Nondestructive Metabolomic Fingerprinting: FTIR, NIR and Raman Spectroscopy in Food Screening.
In recent years, there has been renewed interest in the maintenance of food quality and food safety on the basis of metabolomic fingerprinting using vibrational spectroscopy combined with multivariate chemometrics. Nontargeted spectroscopy techniques such as FTIR, NIR and Raman can provide fingerprint information for metabolomic constituents in agricultural products, natural products and foods in a high-throughput, cost-effective and rapid way. In the current review, we tried to explain the capabilities of FTIR, NIR and Raman spectroscopy techniques combined with multivariate analysis for metabolic fingerprinting and profiling. Previous contributions highlighted the considerable potential of these analytical techniques for the detection and quantification of key constituents, such as aromatic amino acids, peptides, aromatic acids, carotenoids, alcohols, terpenoids and flavonoids in the food matrices. Additionally, promising results were obtained for the identification and characterization of different microorganism species such as fungus, bacterial strains and yeasts using these techniques combined with supervised and unsupervised pattern recognition techniques. In conclusion, this review summarized the cutting-edge applications of FTIR, NIR and Raman spectroscopy techniques equipped with multivariate statistics for food analysis and foodomics in the context of metabolomic fingerprinting and profiling.


Donor scoring system for cadaveric renal transplantation.
We studied early renal function in 241 consecutive patients who received cadaveric renal transplants at two different transplantation centers (group 1, n = 90; group 2, n = 151). Univariate and multivariate analyses of data from group 1 showed a significant correlation between seven donor variables and early renal function after cadaveric renal transplantation. A scoring system was developed from these seven donor variables (cause of death, 0-6 points; history of hypertension, 0-6; final creatinine clearance before procurement, 0-6; age, 0-6; history of diabetes mellitus, 0-3; cold ischemia time, 0-3; and severity of renal artery plaque, 0-3). Data from group 2 were used to validate the donor scoring system and stratify cadaver kidneys on the basis of score: grade A, 0-5 points; grade B, 6-10; grade C, 11-15; and grade D, 16-32. A significant decline in early renal function was observed with increasing donor score and grade of cadaver kidney. In conclusion, a donor scoring system based on information available at the time of procurement can be used to estimate early graft function after cadaveric renal transplantation and may assist in the allocation of marginal organs.


Elevated Serum Ferritin Levels Are Predictive of Renal Function Recovery among Patients with Acute Kidney Injury.
Oxidative stress (OS) frequently contributes to the development of acute kidney injury (AKI). Iron can promote oxidative stress and tissue injury by catalyzing free reactive oxygen species (ROS) generation and increasing the steady-state concentration of these potent oxidants. The anticipated role of ferritin is to protect from OS by sequestering iron and limiting its involvement in reactions that generate ROS. In this prospective study, we aimed to investigate the association between serum ferritin levels and kidney function recovery among patients with AKI. Renal recovery was determined as a return of serum creatinine to less than 1.25 times the baseline value after 90 days of follow-up. One hundred twelve patients (72 males and 40 females, 63.68 ± 10.6 years old) were included in the final analysis. They were divided into AKI recovery (n = 76) and non-recovery groups (n = 36). Ferritin levels on admission were higher in AKI recovery group [284 (IQR 153-525) ng/mL] compared with the non-recovery group [127.4 (IQR 30-243) ng/mL], p < 0.001. Serum ferritin levels and the renal recovery significantly positively correlated (r = 0.72, p < 0.001). In multiple linear regression analysis, higher serum ferritin was associated with renal function recovery (OR 3.68, CI 2.02-3.97, p < 0.001). The optimal cut-off point of 240.5 ng/mL was determined for serum ferritin, which showed a sensitivity of 75.8% and a positive predictive value of 90%. In conclusion, serum ferritin levels on admission may be used as a prognostic marker for predicting renal recovery in AKI patients.


Increased Outer Membrane Vesicle Formation in a Helicobacter pylori tolB Mutant.
Multiple studies have established the importance of the tol-pal gene cluster in bacterial cell membrane integrity and outer membrane vesicle (OMV) formation in Escherichia coli. In contrast, the functions of Tol-Pal proteins in pathogenic organisms, including those of the Epsilonproteobacteria, remain poorly if at all defined. The aim of this study was to characterize the roles of two key components of the Tol-Pal system, TolB and Pal, in OMV formation in the pathogenic bacterium, Helicobacter pylori. H. pylori ΔtolB, Δpal and ΔtolBpal mutants, as well as complemented strains, were generated and assessed for changes in morphology and OMV production by scanning electron microscopy and enzyme-linked immunoassay (ELISA), respectively. The protein content and pro-inflammatory properties of OMVs were determined by mass spectroscopy and interleukin-8 (IL-8) ELISA on culture supernatants from OMV-stimulated cells, respectively. H. pylori ΔtolB and Δpal bacteria exhibited aberrant cell morphology and/or flagella biosynthesis. Importantly, the disruption of H. pylori tolB but not pal resulted in a significant increase in OMV production. The OMVs from H. pylori ΔtolB and Δpal bacteria harbored many of the major outer membrane and virulence proteins observed in wild-type (WT) OMVs. Interestingly, ΔtolB, Δpal and ΔtolBpal OMVs induced significantly higher levels of IL-8 production by host cells, compared with WT OMVs. This work demonstrates that TolB and Pal are important for membrane integrity in H. pylori. Moreover, it shows how H. pylori tolB-pal genes may be manipulated to develop "hypervesiculating" strains for vaccine purposes.


Systemic Inflammation during and after Bronchiectasis Exacerbations: Impact of Pseudomonas aeruginosa.
Bronchiectasis is a chronic structural disease associated with exacerbations that provoke systemic inflammation. We aimed to evaluate the systemic acute proinflammatory cytokine and its biomarker profiles during and after exacerbations and its relationship with the severity of episode, microbiological findings, and the bronchiectasis severity index. This prospective observational study compared exacerbation and stable groups. Cytokine (interleukins (IL)-17a, IL-1β, IL-6, IL 8; tumor necrosis factor-alpha (α)) and high-sensitivity C-reactive protein (hsCRP) levels were determined by multiplex analysis on days 1, 5, 30, and 60 in the exacerbation group and on day 1 in the stable group. We recruited 165 patients with exacerbations, of which 93 were severe (hospitalized). Proinflammatory systemic IL-17a, IL-1β, IL-8, and tumor necrosis factor-α levels increased similarly on days 1 and 5 in severe and non-severe episodes, but on day 30, IL-17a, IL-8, and IL-6 levels were only increased for severe exacerbations. The highest IL-17a level occurred in patients with chronic plus the acute isolation of Pseudomonas aeruginosa. At 30 days, severe exacerbations were independently associated with higher levels of IL-17 (Odds ratio (OR) 4.58), IL-6 (OR 4.89), IL-8 (OR 3.08), and hsCRP (OR 6.7), adjusted for age, the bronchiectasis severity index, and treatment duration. Exacerbations in patients with chronic P. aeruginosa infection were associated with an increase in IL-17 and IL-6 at 30 days (ORs 7.47 and 3.44, respectively). Severe exacerbations elicit a higher systemic proinflammatory response that is sustained to day 30. Patients with chronic P. aeruginosa infection had impaired IL-17a reduction. IL-17a could be a useful target for measuring systemic inflammation.


A large scale study of the psychometric characteristics of the IBR Modified Overt Aggression Scale: findings and evidence for increased self-destructive behaviors in adult females with autism spectrum disorder.
The psychometric characteristics of the IBR Modified Overt Aggression Scale were studied in over 2,000 people with Intellectual Disability (ID). Reliability ranged from good to excellent. Aggression toward others and objects was highest in the youngest adults, in those in the moderate to severe range of ID, and in those with an autism spectrum diagnosis. Self-injury was highest in those in the severe to profound range of ID and in those with autism, particularly the females. Females with autism were also more likely to make the most self-deprecating statements. Our data suggest that adult females with autism are a unique group and support the notion that mood and anxiety disorders play a role in self-destructive behaviors in this population.


[The possibility of forensic medical assessment of the damage to clothes caused by a blank shots with the MP-79-9TM pistol].
The authors undertook an analysis of constructional features of standard blank and non-lethal cartridges for the MP-79-9TM pistol. The composition of gunshot products and the maximum distance over which they propagate have been determined. Special attention is given to the peculiarities of the damage caused to the target cloths (cotton and woolen) by blank rounds shot from different distances. A new chemical method was used for the first time to detect the particles of gunpowder on the victim's cloth; the possibility of its application for differential diagnostics of gunshot damages inflicted by blank and traumatic cartridges affected from different distances was estimated.


Oscillatory flows induced by microorganisms swimming in two dimensions.
We present the first time-resolved measurements of the oscillatory velocity field induced by swimming unicellular microorganisms. Confinement of the green alga C. reinhardtii in stabilized thin liquid films allows simultaneous tracking of cells and tracer particles. The measured velocity field reveals complex time-dependent flow structures, and scales inversely with distance. The instantaneous mechanical power generated by the cells is measured from the velocity fields and peaks at 15 fW. The dissipation per cycle is more than 4 times what steady swimming would require.


[Preoxygenation and upper airway patency control].
During preoperative assessment, risk factors of upper airway obstruction should be evaluated: respiratory insufficiency, low O(2) reserve, preoxygenation failure or difficult face mask ventilation. In healthy subjects, spontaneous breathing O(2) for 3 min is the reference method. Apnoea duration is longer after preoxygenation than after denitrogenation, even if FEO(2) and SpO(2) do not change during the two last minutes of preoxygenation. The apnea time is longer after 3 min spontaneous breathing than after four deep breaths for 1 min in most of the literature. Maximal breathing during 2 min can produce values comparable to those obtained with tidal volume breathing for 3 min. FEO(2) monitoring is helpful in the assessment of preoxygenation quality: In case of oxygenation impairment during anaesthesia induction, algorithm use is helpful. Because desperate emergencies will occur in association with anaesthesia, every location should have the immediate availability of Fastrach and trans tracheal ventilation. Every anaesthesiologist should be familiar with and well practised in a variety of airway management techniques. Teaching programs are organised in order to develop anaesthesiologist sensitisation and skill.


A gene required for RNase P activity in Candida (Torulopsis) glabrata mitochondria codes for a 227-nucleotide RNA with homology to bacterial RNase P RNA.
We have mapped a gene in the mitochondrial DNA of Candida (Torulopsis) glabrata and shown that it is required for 5' end maturation of mitochondrial tRNAs. It is located between the tRNAfMet and tRNAPro genes, the same tRNA genes that flank the mitochondrial RNase P RNA gene in the yeast Saccharomyces cerevisiae. The gene is extremely AT rich and codes for AU-rich RNAs that display some sequence homology with the mitochondrial RNase P RNA from S. cerevisiae, including two regions of striking sequence homology between the mitochondrial RNAs and the bacterial RNase P RNAs. RNase P activity that is sensitive to micrococcal nuclease has been detected in mitochondrial extracts of C. glabrata. An RNA of 227 nucleotides that is one of the RNAs encoded by the gene that we mapped cofractionated with this mitochondrial RNase P activity on glycerol gradients. The nuclease sensitivity of the activity, the cofractionation of the RNA with activity, and the homology of the RNA with known RNase P RNAs lead us to propose that the 227-nucleotide RNA is the RNA subunit of the C. glabrata mitochondrial RNase P enzyme.


Annotating whole genome variants and constructing a multi-classifier based on samples of ADNI.
Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder in the elderly, which will eventually lead to dementia without an effective precaution and treatment. As a typical complex disease, the mechanism of AD's occurrence and development still lacks sufficient understanding. In this study, we aim to directly analyze the relationship between DNA variants and phenotypes based on the whole genome sequencing data. Firstly, to enhance the biological meanings of our study, we annotate the deleterious variants and mapped them to nearest protein coding genes. Then, to eliminate the redundant features and reduce the burden of downstream analysis, a multi-objective evaluation strategy based on entropy theory is applied for ranking all candidate genes. Finally, we use multi-classifier XGBoost for classifying unbalanced data composed with 46 AD samples, 483 mild cognitive impairment (MCI) samples and 279 cognitive normal (CN) samples. The experimental results on real whole genome sequencing data from Alzheimer's Disease Neuroimaging Initiative (ADNI) show that our method not only has satisfactory classification performance but also finds significance correlation between AD and RIN3, a known susceptibility gene of AD. In addition, pathway enrichment analysis was carried out using the top 20 feature genes, and three pathways were confirmed to be significantly related to the formation of AD. From the experimental results, we demonstrated that the efficacy of our proposed method has practical significance.


An investigation of heterochromatin domains on the fourth chromosome of Drosophila melanogaster.
The banded portion of Drosophila melanogaster chromosome 4 exhibits euchromatic and heterochromatic characteristics. Reminiscent of heterochromatin, it contains a high percentage of repetitive elements, does not undergo recombination, and exhibits high levels of HP1 and histone-3 lysine-9 dimethylation. However, in the distal 1.2 Mb, the gene density is typical of euchromatin, and this region is polytene in salivary gland nuclei. Using P-element reporters carrying a copy of hsp70-white, alternative chromatin packaging domains can be distinguished by the eye color phenotype. Mapping studies identified the repetitive element 1360 as a candidate for heterochromatin targeting in the fourth chromosome Hcf region. We report here two new screens using this reporter to look for additional heterochromatin target sites. We confirm that reporter elements within 10 kb of 1360 are usually packaged as heterochromatin; however, heterochromatin packaging occurs in the sv region in the absence of 1360. Analyses of the sequences adjacent to P-element reporters show no simple association between specific repeated elements and transgene expression phenotype on a whole chromosome level. The data require that heterochromatin formation as a whole depends on a more complex pattern of sequence organization rather than the presence of a single sequence element.


Incidence and risk factors for stroke in type 2 diabetic patients: the DAI study.
Type 2 diabetes mellitus is a strong predictor of cerebrovascular disease, yet few studies have assessed the incidence of stroke and the role of other risk factors in unselected type 2 diabetes mellitus populations. We prospectively followed-up 14,432 type 2 diabetes mellitus patients, aged 40 to 97 years, with and without a history of cardiovascular disease at enrollment, and we estimated the incidence of stroke and the hazards ratios with respect to clinical variables. During a 4-year follow-up, 296 incident stroke events were recorded. In persons with no history of cardiovascular disease, the age-standardized incidence of stroke (per 1000 person-years) was 5.5 (95% confidence interval, 4.2 to 6.8) in men and 6.3 (95% confidence interval, 4.5 to 8.2) in women. In persons with a history of cardiovascular disease, it was 13.7 (95% confidence interval, 7.5 to 19.8) in men and 10.8 (95% confidence interval, 7.3 to 14.4) in women. The hazards ratios of stroke incidence varied according to age, sex, and history of cardiovascular disease. Among men with no history, HbA1c and smoking were predictors of stroke. Among patients with a history, the risk factors were, in men, therapy with insulin plus oral agents, treated high total cholesterol and low HDL cholesterol, whereas in women microvascular complications were a risk factor. Previous stroke was a strong predictor of stroke in both sexes. Age and previous stroke are the main predictors of stroke in diabetes. The combined role of Hba1c, microvascular complications, low HDL cholesterol, and treatment with insulin plus oral agents highlights the importance of diabetic history and clinical background in the development of stroke.


Student use and perceptions of different learning aids in a problem-based learning (PBL) dentistry course.
First-year dental students in a new problem-based learning (PBL) course, the Bachelor of Dentistry (BDent) Program at the University of Sydney, Australia, completed the Study Process Questionnaire and two other questionnaires in this study. The study aimed to identify student perceptions of a written formative assessment and the helpfulness of various learning aids used to prepare for this assessment and preparing to be a dental clinician. Correlations between approach to learning and perceptions of assessment and learning aids showed theoretically expected associations. Surface learning was associated with students' concerns regarding whether assessment items reflected curriculum content, a valuing of lectures as a learning aid, and low scores for theme sessions. Deep learning was associated with a perception that the assessment tested application of basic and clinical sciences and a valuing of both independent study groups and learning topics as learning aids. An achievement orientation to learning was associated with a valuing of formative assessment as a learning aid and an intention to modify study habits as a result of participating in formative assessment. The findings provide insight into student learning in a PBL context that will help teachers and curriculum developers better understand the value of teaching aids provided in the program and the impact assessment has on study styles.


Diagnostic Performance of Deep Learning Models for Gastric Intestinal Metaplasia Detection in Narrow-band Images.
Gastric Intestinal Metaplasia (GIM) is one of the precancerous conditions in the gastric carcinogenesis cascade and its optical diagnosis during endoscopic screening is challenging even for seasoned endoscopists. Several solutions leveraging pre-trained deep neural networks (DNNs) have been recently proposed in order to assist human diagnosis. In this paper, we present a comparative study of these architectures in a new dataset containing GIM and non-GIM Narrow-band imaging still frames. We find that the surveyed DNNs perform remarkably well on average, but still measure sizeable inter-fold variability during cross-validation. An additional ad-hoc analysis suggests that these baseline architectures may not perform equally well at all scales when diagnosing GIM.Clinical relevance- Enhanching a clinician's ability to detect and localize intestinal metaplasia can be a crucial tool for gastric cancer management policies.


Chronic behavioral testing after focal ischemia in the mouse: functional recovery and the effects of gender.
Several useful behavioral tests exist for measuring behavioral recovery after ischemia in higher-order animals and rats. With the increasing use of mice in focal stroke research, simple, reliable, and reproducible behavioral testing has become a priority. As neuroprotective agents are tested, long-term outcome must be assessed, especially in studies focused on neuronal plasticity and regeneration after ischemia. Our laboratory and others have previously shown that estrogen (E2) is neuroprotective in rodent stroke paradigms. We examined a battery of behavioral tests in male and female mice subjected to 90 min of middle cerebral artery occlusion (MCAO) to determine the most sensitive tests for detecting sensorimotor dysfunction after stroke, and to determine the functional significance of E2-mediated neuroprotection. Only two tests, the corner test and the cylinder test, were able to differentiate between groups (sham and stroke) after several days of repeated testing. The cylinder test was sensitive to the neuroprotective/neurorestorative effects of E2, but 2 weeks after stroke, the cylinder test was unable to distinguish between sham and stroke animals treated with E2. In contrast, the corner test was able to differentiate stroke and sham animals even 6 weeks after stroke, but did not distinguish animals treated with E2 vs. vehicle. These tests provide a simple, rapid, reliable assessment of sensorimotor dysfunction in the mouse after focal ischemia. Hormonal status influences speed of recovery on cylinder testing in animals of both genders. This suggests that a short battery of tests including the neurological score, cylinder, and corner test may be adequate to rapidly and repeatedly assess sensorimotor dysfunction in mice of both genders.


Plasticizer acetyl triethyl citrate (ATEC) induces lipogenesis and obesity.
Environmental chemicals, such as plasticizers, have been linked to increased rates of obesity, according to epidemiological studies. Acetyl triethyl citrate (ATEC) is a plasticizer that is commonly utilized in pharmaceutical products and food packaging as a non-phthalate alternative. Due to its direct contact with the human body and high leakage rate from the polymers, assessment of the potential risk of ATEC exposure at environmentally relevant low doses to human health is needed. Male C57BL/6 J mice were fed diets containing ATEC at doses of either 0.1 or 10 μg/kg per day in a period of 12 weeks to mimic the real exposure environment. The findings suggest that in C57BL/6 J mice, ATEC exposure resulted in increased body weight gain, body fat percentage, and benign hepatocytes, as well as adipocyte size. Consistent with in vivo models, ATEC treatment obviously stimulated the increase of intracellular lipid load in both mouse and human hepatocytes. Mechanically, ATEC induced the transcriptional expression of genes involved in de novo lipogenesis and lipid uptake. Using both enzyme inhibitor and small interfering RNA (siRNA) transfection, we found that stearoyl-coenzyme A desaturase 1 (SCD1) played a significant role in ATEC-induced intracellular lipid accumulation. This study for the first time provided initial evidence suggesting the obesogenic and fatty liver-inducing effect of ATEC at low doses near human exposure levels, and ATEC might be a potential environmental obesogen and its effect on human health need to be further evaluated.


Impact of lymphadenectomy on the treatment of endometrial cancer using data from the JSOG cancer registry.
Regional lymph node (LN) dissection is a standard surgical procedure for endometrial cancer, but there is currently no clear consensus on its therapeutic significance. We aimed to determine the impact of regional LN dissection on the outcome of endometrial cancer. Study subjects comprised 36,813 patients who were registered in the gynecological tumor registry of the Japan Society of Obstetrics and Gynecology, had undergone initial surgery for endometrial cancer between 2004 and 2011, and whose clinicopathological factors and prognosis were appropriate for our investigation. The following clinicopathological factors were obtained from the registry: age, surgical stage classification, Union for International Cancer Control tumor, node, metastasis classification, histological type, histological differentiation, presence or absence of LN dissection, and postoperative treatment. We retrospectively analyzed the clinicopathological factors and therapeutic outcomes for patients with endometrial cancer. Analysis of all subjects showed that the group that underwent LN dissection had a significantly better overall survival than the group that did not undergo dissection. Analysis based on stage showed similar results across groups, except for stage Ia. Analysis based on stage and histological type showed similar results across groups, except for stage Ia endometrial carcinoma G1 or Ia G2. Multivariate analysis of prognostic factors indicated that LN dissection is an independent prognostic factor and that it has a greater impact on prognosis than adjuvant chemotherapy. Despite the limitations of a retrospective study with some biases, the results suggest that LN dissection in endometrial cancer has a prognostic effect.


Internet- and App-Based Stress Intervention for Distance-Learning Students With Depressive Symptoms: Protocol of a Randomized Controlled Trial.
Background: Mental disorders are highly prevalent among university students. Distance-learning students are particularly burdened and have limited access to conventional university health services. Interventions for stress are sought after in distance learners and may help increase treatment coverage. Internet-based interventions have been shown to be effective in preventing and treating depression, but it remains unclear if interventions directed at academic stress also have this potential. Aim: The trial presented here investigates the effectiveness of an Internet- and App-based stress intervention in distance-learning students with elevated levels of depression. Methods: A sample of N = 200 students of a large German distance university with elevated levels of depression [Center for Epidemiological Studies' Depression Scale (CES-D) ≥ 16] will be randomly assigned to either an Internet- and App-based stress management intervention group (IG) or a control group (CG) receiving an Internet-based psychoeducational program for academic stress. The IG consists of eight Internet-based sessions promoting stress management skills using cognitive-behavioral and problem-solving techniques. A mobile App will be employed to facilitate training transfer. Self-report data will be assessed at baseline (T0), post-treatment (T1; 7 weeks), and 3-month follow-up (T2). Potential moderators will be assessed at baseline. The primary outcome is depression (CES-D) post-treatment. Secondary outcomes include mental health outcomes, modifiable risk and protective factors, and academic outcomes. Data will be analyzed on an intention-to-treat principle along with sensitivity analyses to assess the robustness of findings. Additional health economic analyses will be conducted. Discussion: Results will provide the basis to assess the acceptance and effectiveness of Internet-delivered stress interventions in distance-learning students with symptoms of depression. Ethics and dissemination: The study has been reviewed and approved by the University of Erlangen-Nuremberg ethics committee (Erlangen, Germany; 33_17 Bc). Results of the study will be disseminated through peer-reviewed publications. Trial Registration: German Clinical Trial Registration (DRKS), identifier DRKS00011800.


Tropomyosin antibody: the specific localization of tropomyosin in nonmuscle cells.
An antibody against purified chicken skeletal muscle tropomyosin is used in indirect immunofluorescence to visualize the localization of tropomyosin in a variety of nonmuscle cells. The antibody produces a fluorescent pattern which is very similar to that obtained with an actin-specific antibody. This pattern is composed of fluorescent fibers which are shown to be coincident with the fibers seen with phase-contrast optics. High resolution epifluorescent microscopy reveals that fibers stained with the actin antibody show a continuous fluorescence, while fibers reacted with the tropomyosin antibody show a periodic fluorescence. Measurements indicate that the lengths of the fluorescent segments are variable with an average of 1.2 mum while the spacing between segments is approximately 0.4 mum.


Outcome after prenatal diagnosis of the hypoplastic left heart syndrome.
To derive accurate survival figures in the current surgical era for counselling in early pregnancy after the diagnosis of fetal hypoplastic left heart syndrome. A tertiary referral centre for paediatric cardiology and cardiac surgery. A retrospective study of the outcome in all cases of hypoplastic left heart syndrome presenting in fetal life between mid-1993 and the end of 1996. The diagnosis was made in 30 fetuses. In four of 12 identified before 24 weeks' gestation the mothers chose to terminate the pregnancy. There was an intention to treat in 24 of the remaining fetuses. Survival to six months of postnatal life. Of the 24 infants, five were not offered Norwood stage 1 because of trisomy 18 (n = 2), unfavourable cardiac anatomy (n = 2), or neurological impairment (n = 1). One further infant did not survive to cardiac surgery after gastrointestinal surgery. Of the remaining 18 patients, eight had features that were considered to increase the risk of surgical repair. Of the 18 patients who underwent Norwood stage 1, there were nine survivors. There was a survival rate of 70% in infants undergoing surgery with no complicating features, a 50% survival of the all surgical candidates, and 37.5% survival from an intention to treat position. At the initial diagnosis of fetal hypoplastic left heart syndrome, the overall survival appears to be less than 40%. Evaluation must include detailed extracardiac and intracardiac assessment to predict the risks of surgical treatment. Prenatal counselling can be modified as pregnancy advances, depending on the detection or exclusion of complicating factors.


Corrination mitigates peptide aggregation as exemplified for Glucagon.
Pharmaceutical development of glucagon for use in acute hypoglycemia has proved challenging, due in large part to poor solubility, poor stability and aggregate formation. Herein, we describe highly soluble, low aggregating, glucagon conjugates generated through use of the commercially available vitamin B12precursor dicyanocobinamide ('corrination'), which retain full stimulatory action at the human glucagon receptor. The modified glucagon analogs were tested in a chemical stability assay in 50mM phosphate buffer and the percentage of original concentration retained was determined after two weeks of incubation at 37 ˚C. Aggregate formation assays were also performed after 48hours of agitation at 37 ˚C using a thioflavin (ThT) fluorescence-based assay. All corrinated compounds retained original concentration to a higher degree than glucagon controls and showed markedly decreased aggregation compared to their respective noncorrinated analogues. Based on the statistically significant increase in chemical stability coupled with the notably decreased tendency to form aggregates, analogues 2 and its corrinated conjugate 5 were used for a functional assay study performed after agitation at 37 ˚C for 24-hr after which in agonism was measured at the human glucagon receptor agonism using a cAMP FRET assay. Corrinated 5 exhibited a 6.6-fold increased potency relative to glucagon, which was shown to have a 165-fold reduction in potency. The relative potency of 5 was also improved compared to that of 2 with EC50 values of 5.5nM and 9.6nM for 5 and 2, respectively. In conclusion, corrination of peptides mitigrates aggregation, presenting a compound with prolonged stability and agonism as demonstrated for glucagon.


The actin filament severing protein actophorin promotes the formation of rigid bundles of actin filaments crosslinked with alpha-actinin.
The actin filament severing protein, Acanthamoeba actophorin, decreases the viscosity of actin filaments, but increases the stiffness and viscosity of mixtures of actin filaments and the crosslinking protein alpha-actinin. The explanation of this paradox is that in the presence of both the severing protein and crosslinker the actin filaments aggregate into an interlocking meshwork of bundles large enough to be visualized by light microscopy. The size of these bundles depends on the size of the containing vessel. The actin filaments in these bundles are tightly packed in some areas while in others they are more disperse. The bundles form a continuous reticulum that fills the container, since the filaments from a particular bundle may interdigitate with filaments from other bundles at points where they intersect. The same phenomena are seen when rabbit muscle aldolase rather than alpha-actinin is used as the crosslinker. We propose that actophorin promotes bundling by shortening the actin filaments enough to allow them to rotate into positions favorable for lateral interactions with each other via alpha-actinin. The network of bundles is more rigid and less thixotropic than the corresponding network of single actin filaments linked by alpha-actinin. One explanation may be that alpha-actinin (or aldolase) normally in rapid equilibria with actin filaments may become trapped between the filaments increasing the effective concentration of the crosslinker.


Hypokalemia Promotes Arrhythmia by Distinct Mechanisms in Atrial and Ventricular Myocytes.
Hypokalemia occurs in up to 20% of hospitalized patients and is associated with increased incidence of ventricular and atrial fibrillation. It is unclear whether these differing types of arrhythmia result from direct and perhaps distinct effects of hypokalemia on cardiomyocytes. To investigate proarrhythmic mechanisms of hypokalemia in ventricular and atrial myocytes. Experiments were performed in isolated rat myocytes exposed to simulated hypokalemia conditions (reduction of extracellular [K+] from 5.0 to 2.7 mmol/L) and supported by mathematical modeling studies. Ventricular cells subjected to hypokalemia exhibited Ca2+ overload and increased generation of both spontaneous Ca2+ waves and delayed afterdepolarizations. However, similar Ca2+-dependent spontaneous activity during hypokalemia was only observed in a minority of atrial cells that were observed to contain t-tubules. This effect was attributed to close functional pairing of the Na+-K+ ATPase and Na+-Ca2+ exchanger proteins within these structures, as reduction in Na+ pump activity locally inhibited Ca2+ extrusion. Ventricular myocytes and tubulated atrial myocytes additionally exhibited early afterdepolarizations during hypokalemia, associated with Ca2+ overload. However, early afterdepolarizations also occurred in untubulated atrial cells, despite Ca2+ quiescence. These phase-3 early afterdepolarizations were rather linked to reactivation of nonequilibrium Na+ current, as they were rapidly blocked by tetrodotoxin. Na+ current-driven early afterdepolarizations in untubulated atrial cells were enabled by membrane hyperpolarization during hypokalemia and short action potential configurations. Brief action potentials were in turn maintained by ultra-rapid K+ current (IKur); a current which was found to be absent in tubulated atrial myocytes and ventricular myocytes. Distinct mechanisms underlie hypokalemia-induced arrhythmia in the ventricle and atrium but also vary between atrial myocytes depending on subcellular structure and electrophysiology.


Organic and Inorganic Analysis of Rhaphidophora pinnata (l.f.) Schott Water Extract.
Rhaphidophora pinnata (L.f.) Schott is one of the Indonesian plants, has known as a medicinal plant. This plant is a vine; round stems have sticky roots and hanging roots. The leaves have been used as traditional anticancer in Singapore. Indonesian people have also used R. pinnata plants as a diuretic agent, anticancer and antibacterial. R. pinnata plants contain active substances from alkaloid compounds, flavonoids, saponins, tannins and triterpenoids/steroids. The purpose of this study was to determine the organic and inorganic content of Rhaphidophora pinnata (L.f.) Schott water extract in the form of fresh leaves, micro simplicia and nano simplicia. The collected R. pinnata leaves are drained and grinded to make micro, and nano Simplicia powder of R. pinnata leaves. The size characterisation of R. pinnata leaves was analysing using Particles Size Analyzer. The water extract of R. pinnata leaves, micro simplicia, and nano simplicia R. pinnata leaves was made 10% (w / v) in water. Phytochemical screening of nano simplicia and nano simplicia water extract included an examination of alkaloid compounds, flavonoids, saponins, tannins, glycosides, and steroids/triterpenoids. Thin-layer chromatography analysis of water extract was analysed using TLC scanner. The element that contains in the water extract was analysed using atomic absorption spectrophotometry methods. The results of phytochemical screening of nano simplicia powder and nano simplicia water extract showed the presence of flavonoids, alkaloids, saponins, tannins, and glycosides. Eluent, which shows good elution is n-butanol: acetic acid: water (6: 2: 2). This eluent is used to elute polar and semipolar compounds and is very good for separating flavonoids. R. pinnata water extract contains the minerals potassium, sodium, magnesium and calcium. R. pinnata water extract contains organic compounds in the form of flavonoids, alkaloids, saponins, tannins, and glycosides. The nano simplicia water extract showed more chemical content than other water extracts on the TLC plate by detection at a wavelength of 250 nm and 300 nm. The most element content in R. pinnata water extract is potassium, followed by magnesium, sodium, and calcium.


A personalized and optimal approach for dosing contrast material at coronary computed tomography angiography.
A method for constructing a personalized contrast medium protocol at contrast enhanced, Coronary CT Angiography (CCTA) is presented. A one compartment pharmacokinetic model is parameterized and identified with a minimal data set from a test-bolus injection. A direct-search optimization is performed to construct a protocol that achieves target enhancement in the cardiac structures. Clinical results demonstrating the method's ability to achieve prospectively chosen image enhancement levels while reducing contrast medium dose are presented.


[Correlation between the lymphocyte surface potential and membrane potential in various physiological states].
Present work shows that changes in the surface potential (SP) are linearly connected with alterations of the cell membrane potential (MP) at three physiological states of the organism: control (C), induced cancerogenesis (IC) and total reaction of the organism to damage (TRD). In the control greater SP changes are corresponded with the least MP changes. When SP is changed almost by 100%, MP change is about 20%. In the course of TRD development a reverse relationship is observed: 20% change of the charge is corresponded by a practically 100% change of MP. The relationship indices of MP and SP change in the course of TRD and in the control are equal: with a decrease of MP the lymphocyte SP is also decreased. At the initial stages of IC development the relationship index of MP with SP is changed. In this case a 20% decrease of SP is accompanied by a 60% increase of MP.


First biocompatibility margins for optical stimulation at the eardrum via 532-nm laser pulses in a mouse model.
Hearing impairment affects ∼460 million people worldwide. Conservative therapies, such as hearing aids, bone conduction systems, and middle ear implants, do not always sufficiently compensate for this deficit. The optical stimulation is currently under investigation as an alternative stimulation strategy for the activation of the hearing system. To assess the biocompatibility margins of this emerging technology, we established a method applicable in whole-mount preparations of murine tympanic membranes (TM). We irradiated the TM of anesthetized mice with 532-nm laser pulses at an average power of 50, 89, 99, and 125 mW at two different locations of the TM and monitored the hearing function with auditory brainstem responses. Laser-power-dependent negative side effects to the TM were observed at power levels exceeding 89 mW. Although we did not find any significant negative effects of optical stimulation on the hearing function in these mice, based on the histology results further studies are necessary for optimization of the used parameters.


Adverse childhood experiences, mental health, and quality of life of Chilean girls placed in foster care: An exploratory study.
In Latin America, little research has been conducted regarding exposure to adverse childhood experiences (ACEs), mental health, and health-related quality of life (HRQoL) among foster children. This study examined the association between ACEs and mental health, posttraumatic stress disorder (PTSD), and HRQoL in Chilean foster girls relative to age-matched Chilean family girls. Data were obtained from 27 Chilean foster girls and 27 Chilean girls ages 6 to 17 years living in family homes. Standardized self- and proxy-report measures were used. Foster girls reported more ACEs than controls in terms of familial and nonfamilial sexual abuse and both emotional and physical neglect. Girls living in foster care had a significantly higher rate of PTSD, displayed greater behavioral and emotional problems, and reported a lower HRQoL. Analysis confirmed the well-known cumulative risk hypothesis by demonstrating a significant positive association between the number of ACEs and PTSD symptom severity and a significant negative association with HRQoL. Chilean foster girls endured more ACEs that impair mental health and HRQoL than age-matched peers living with their families. These findings have implications for out-of-home care services in Latin America, highlighting the need to implement not only appropriate trauma-focused treatments but also appropriate prevention strategies.


An unusual cause of recurrent falls in an older gentleman.
The authors present the case of an 82-year-old gentleman who was admitted through Accident & Emergency with a history of increasingly recurrent falls. A thorough history and examination led to the provisional diagnosis of cervical cord compression. Subsequent investigations confirmed an erosive abnormality around the odontoid peg, with an adjacent soft tissue mass. The patient underwent a partial odontoidectomy and the histological examination of the pannus revealed a basophilic crystalline arthropathy, consistent with pseudogout.


Assessing the function of the Ro ribonucleoprotein complex using Caenorhabditis elegans as a biological tool.
The Ro ribonucleoprotein complex (Ro RNP) was initially described as an autoimmune target in human diseases such as systemic lupus erythematosus and Sjögren's syndrome. In Xenopus and human cells, its general structure is composed of one major protein of 60 kDa, Ro60, that binds to one of four small RNA molecules, designated Y RNAs. Although no function has been assigned to the Ro RNP, Ro60 has been shown to bind mutant 5S ribosomal RNA (rRNA) molecules in Xenopus oocytes, suggesting a role for Ro60 in 5S rRNA biogenesis. Ro60 has also been shown to participate in the regulation of the translational fate of the L4 ribosomal protein mRNA by interacting with the 5' untranslated region, again suggesting its possible implication in ribosome biogenesis. To identify the function of Ro RNP, we have taken a genetic approach in the nematode Caenorhabditis elegans. As such, we characterized the gene encoding the protein ROP-1, the homologue of the human Ro60 protein. Here, we review the phenotypic analysis of C. elegans rop-l(-) mutants and integrate these results into a model for the function of the Ro RNP particle.


Causes of cross-over in unilateral neglect: between-group comparisons, within-patient dissociations and eye movements.
Patients with left unilateral neglect bisect long horizontal lines to the right of the true centre. However, when given short lines, many of the same patients mark the midpoint to the left of the true centre, towards the otherwise neglected space. This paradoxical phenomenon has been termed 'cross-over' and is difficult to explain based on current accounts of the neglect syndrome. To explore the causes of cross-over, in a first study we evaluated bisection of 20, 100 and 200 mm horizontal lines in groups of unilateral brain-damaged patients with neglect and hemianopia, with neglect and no hemianopia, with hemianopia and no neglect and without neglect or hemianopia. Cross-over of 20 mm lines was found only in neglect patients with hemianopia. To ascertain further the influence of visual field defects on cross-over, in a second study we compared the performance of two right-brain-damaged patients with contralesional neglect and inferior quadrantanopia with that of a patient with inferior quadrantanopia and no neglect. Patients bisected lines oriented so as to cross or uncross the blind quadrant of the visual field. When short 20 mm lines crossed the blind quadrant, neglect patients showed cross-over; when the same lines crossed the seeing quadrants cross-over was absent. These findings were confirmed by the examination of a neglect patient with sparing of the central 5 degrees of the contralesional left visual hemifield in the right eye and no sparing in the left eye. In monocular viewing, cross-over was present when 20 mm lines were bisected with the left eye and absent when bisected with the right eye. Recording of eye movements showed that at the moment of bisection left eye fixations shifted towards the contralesional line endpoint whereas right eye fixations remained anchored to the centre of the line. With long lines, both eyes deviated ipsilesionally. These results show that in neglect patients ipsilesional deviation in the bisection of long lines turns into apparently paradoxical contralesional bisection of short ones only when these cross a retinotopically blind sector of the neglected space. Cross-over seems to depend on the small spatial effects produced by reflexive contralesional gaze shifts allowing eccentric fixations with the seeing hemifield. During the bisection of long lines, these effects are cancelled out by the strong attentional deviation induced by the marked extension of the ipsilesional line segment. This explanation establishes coherence between cross-over and current accounts of the neglect syndrome.


Bilateral oophorectomy and rate of colorectal cancer: A prospective cohort study.
Worldwide, colorectal cancer is the second most common cancer and third cause of cancer death in women. Estrogen exposure has been inversely associated with colorectal cancer. Oophorectomy reduces circulating estrogen, but the effect on colorectal cancer remains uncertain. The aim of this study was to examine the association between unilateral and bilateral oophorectomy and subsequent risk of colorectal cancer, and whether this association varied by menopausal status at time of oophorectomy, use of hormone replacement therapy (HRT) at baseline, hysterectomy and baseline body mass index (BMI). The study included 25 698 female nurses (aged ≥45 years) participating in the Danish Nurse Cohort. Nurses were followed from baseline until date of colorectal cancer, death, emigration or end of follow-up at December 31, 2018, whichever came first. We examined the association between oophorectomy and colorectal cancer (all ages and stratified by menopausal status). The potential modifying effects of hysterectomy, HRT use at baseline and BMI were investigated. During 542 140 person-years of follow-up, 863 (3.4%) nurses were diagnosed with colorectal cancer. Bilateral oophorectomy was associated with a 79% increased colorectal cancer rate, adjusted rate ratio (aRR) (95% confidence interval [CI]): 1.79 (1.33-2.42). Effect estimates following unilateral oophorectomy also showed higher rate of colorectal cancer, although less pronounced and nonstatistically significant (aRR) (95% CI): 1.25 (0.86-1.82). Similar results were seen when stratifying by menopausal status. The association was not modified by baseline HRT use, hysterectomy or BMI. Oophorectomy was associated with increased rate of colorectal cancer, with highest rates among women with bilateral oophorectomy.


A network analysis based approach to characterizing periodic sharp wave complexes in electroencephalograms of patients with sporadic CJD.
Creutzfeldt-Jacob disease (CJD) is a rapidly progressive, uniformly fatal transmissible spongiform encephalopathy. Sporadic CJD (sCJD) is the most common form of CJD. Electroencephalography (EEG) is one of the main methods to perform clinical diagnosis of CJD, mainly because of periodic sharp wave complexes (PSWCs). In this paper, we propose a network analysis based approach to characterizing PSWCs in EEGs of patients with sCJD. Our approach associates a network with each EEG at disposal and defines a new numerical coefficient and some network motifs, which characterize the presence of PSWCs in an EEG tracing. The new coefficient, called connection coefficient, and the detected network motifs are capable of characterizing the EEG tracing segments with PSWCs. Furthermore, network motifs are able to detect what are the most active and/or connected brain areas in the tracing segments with PSWCs. The results obtained show that, analogously to what happens for other neurological diseases, network analysis can be successfully exploited to investigate sCJD.


Extreme deficiency of L-type pyruvate kinase with moderate clinical expression.
In the erythrocytes and liver of a patient with hereditary non-spherocytic hemolytic anemia and increased serum aminotransferases, almost complete deficiency of L-type pyruvate kinase was detected. The parents of the patient are second cousins and the pyruvate kinase activity in their erythrocytes was decreased to about half normal values. Pyruvate kinase from the patient is characterized by extreme lability. Pyruvate kinase from the parents' red cells showed no molecular abnormalities. No cross-reactive material could be precipitated with a monospecific antibody raised against L-type pyruvate kinase in the patient's erythrocytes. In the red cells of the parents a decreased amount of cross-reactive material against pyruvate kinase antibodies was found, indicating that the lowered pyruvate kinase activity in the erythrocytes of the parents is caused by a decreased level of the pyruvate kinase protein. In the liver of the patient no L-type pyruvate kinase activity and no immunologically recognizable L-type pyruvate kinase could be detected. The increased lability of the enzyme protein may explain the low residual activity. However, this decreased activity is shown to be sufficient to perform a normal glycolytic flux resulting only in moderate clinical expression.


Unsuspected "isolated" dislocation of the radial head in an adult.
We have described a patient who as a child sustained a Monteggia's fracture that was neither diagnosed nor treated. Neurologic deficit and limitation of motion were clinically apparent. A high index of suspicion, careful examination of the patient, and high-quality roentgenograms should enable accurate diagnosis of this and similar lesions in less obvious cases, thus avoiding the complications of missed diagnosis.


Over 4000 nm bandwidth of mid-IR supercontinuum generation in sub-centimeter segments of highly nonlinear tellurite PCFs.
We report broad bandwidth, mid-IR supercontinuum generation using a sub-cm (8 mm) length of highly nonlinear tellurite microstructured photonic crystal fiber (PCF). We pump the fiber at telecommunication wavelengths by using 1550 nm, 100 fs pulses of energy E=1.9 nJ. When coupled in the PCF, these pulses result in a supercontinuum (SC) bandwidth of 4080 nm extending from 789 to 4870 nm measured at 20 dBm below the peak spectral power. This bandwidth is comparable or in excess of previously reported spectra for other nonlinear glass fiber formulations despite the significantly shorter fiber length. In addition, besides offering a convenient pump wavelength, short fiber lengths enable smoother SC spectra, lower dispersion, and reduced material absorption at longer wavelengths making the use of this PCF particularly interesting.


A Simple Method for the Design and Development of Flavivirus NS1 Recombinant Proteins Using an In Silico Approach.
Even in countries that are currently not facing a flavivirus epidemic, the spread of mosquito-borne flaviviruses presents an increasing public threat, owing to climate change, international travel, and other factors. Many of these countries lack the resources (viral strains, clinical specimens, etc.) needed for the research that could help cope with the threat imposed by flaviviruses, and therefore, an alternative approach is needed. Using an in silico approach to global databases, we aimed to design and develop flavivirus NS1 recombinant proteins with due consideration towards antigenic variation. NS1 genes analyzed in this study included a total of 6,823 sequences, from Dengue virus (DENV), Japanese encephalitis virus (JEV), West Nile virus (WNV), Zika virus (ZIKV), and Yellow fever virus (YKV). We extracted and analyzed 316 DENV NS1 sequence types (STs), 59 JEV STs, 75 WNV STs, 30 YFV STs, and 43 ZIKV STs using a simple algorithm based on phylogenetic analysis. STs were reclassified according to the variation of the major epitope by MHC II binding. 78 DENV epitope type (EpT), 29 JEV EpTs, 29 WNV EpTs, 12 YFV EpTs, and 5 ZIKV EpTs were extracted according to their major epitopes. Also, frequency results showed that there were dominant EpTs in all flavivirus. Fifteen STs were selected and purified for the expression of recombinant antigen in Escherichia coli by sodium dodecyl sulfate extraction. Our study details a novel in silico approach for the development of flavivirus diagnostics, including a simple way to screen the important peptide regions.


Macromolecular prodrugs of ribavirin: concerted efforts of the carrier and the drug.
Polymers in tune. Automated parallel polymer synthesis is developed to obtain libraries of macromolecular prodrugs of ribavirin, a broad-spectrum antiviral agent. As many as 10 identified lead polymer conjugates exhibit therapeutic efficacy matching that of the pristine drug and at the same time suppressed the origin of the main side effect of ribavirin.


Nodular Classic Kaposi's Sarcoma Treated With Neodymium-Doped Yttrium Aluminum Garnet Laser Delivered Through a Tilted Angle: Outcome and 12-Month Follow Up.
Classic Kaposi's sarcoma (KS) is a multifocal angioproliferative disorder with a long and indolent course typically affecting the lower extremities of elderly men. Multiple nodules with a rapid growth may sometimes develop, causing pain, bleeding, and discomfort on walking. In such cases, immediate intervention using different methods, including laser therapy, is advisable. We report our experience in classic KS patients with the use of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser delivered through a tilted angle. A total of 81 KS nodules (0.5-3 cm size) located in the feet or lower limbs of nine patients (mean age: 78.8 years; age range: 64-86 years) were selected for treatment with Nd:YAG laser (5-7 mm spot, 140-200 J/cm2 fluence, 5 ms triple pulse with 10 ms delay). The laser beam was delivered at the periphery of each nodule using a tilted angle of 30° to 60° according to lesion size in order to better target the feeding vessels located in the inner and basal depth of the lesion and minimize tissue damage. The treatment outcome was evaluated by clinical photograph, videodermatoscopy, and ultrasound scanning performed before and after treatment, and at each monthly follow-up visit. All treated patients showed full recovery, with negligible scarring, no residual hyperpigmentation, and complete regression of pain. Treatment discomfort was minimal and use of topical anesthetics was not needed. No recurrences were observed at 12-month follow up. Long-pulse Nd:YAG laser delivered using a tilted angle is a fast, easy, effective, comfortable, and safe treatment option available to promptly shrink bulky, painful, or bleeding nodules with minimal discomfort and gives excellent functional and cosmetic results. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.


Expression and Function of Kruppel Like-Factors (KLF) in Carcinogenesis.
Krüppel-like factor (KLF) family members share a three C2H2 zinc finger DNA binding domain, and are involved in cell proliferation and differentiation control in normal as in pathological situations. Studies over the past several years support a significant role for this family of transcription factors in carcinogenesis. KLFs can both activate and repress genes that participate in cell-cycle regulation. Among them, many up-regulated genes are inhibitors of proliferation, whereas genes that promote cell proliferation are repressed. However, several studies do present KLFs as positive regulator of cell proliferation. KLFs can be deregulated in multiple cancers either by loss of heterozygosity (LOH), somatic mutation or transcriptional silencing by promoter hypermethylation. Accordingly, KLF expression was shown to mediate growth inhibition when ectopically expressed in multiple cancer-derived cell lines through the inhibition of a number of key oncogenic signaling pathways, and to revert the tumorogenic phenotype in vivo. Taken together, these observations suggest that KLFs act as tumor suppressor. However, in some occasion, KLFs could act as tumor promoters, depending on "cellular context". Thus, this review will discuss the roles and the functions of KLF family members in carcinogenesis, with a special focus on cancers from epithelial origin.


Telomerase activity in reactive and neoplastic lymphoid tissues: infrequent detection of activity in Hodgkin's disease.
We used the recently described sensitive and rapid detection assay called telomeric repeat amplification protocol (TRAP) to detect telomerase activity in lymphoblastoid (n = 5) and lymphoma cell lines (n = 7), hyperplastic lymph nodes (n = 6) and tonsils (n = 5), and tissues involved by non-Hodgkin's lymphoma (NHL) (n = 43) and Hodgkin's disease (HD) (n = 14). Clearly evident telomerase activity was found in all lymphoblastoid and lymphoma cell lines, and in 34 of 43 cases (80%) of NHL. These results were expected because of the proliferative and immortal nature of the cell lines and most malignant cells. However, positive results were obtained with the TRAP assay in all hyperplastic lymph nodes and tonsils, which raises the issue of derepression of telomerase activity during an immune response. Telomerase activity alone therefore does not distinguish malignant lymphoid proliferations from reactive states. Telomerase activity was detected in only 1 of 14 cases (7%) of lymphoid tissues involved by HD. Eight of the 13 negative cases were considered to be interpretable because of the lack (3 of 13 cases) or low level (5 of 13 cases) of telomerase inhibition. The five remaining cases could not be evaluated because of their telomerase inhibitor content. The findings imply either transient or very low levels of telomerase activity in HD or that HD for the greater part is a telomerase-independent neoplasm. Microdissection studies are needed to identify subsets of cells carrying telomerase activity in both reactive and neoplastic lymphoid tissues.


6-Bromoindirubin-3'-Oxime Regulates Colony Formation, Apoptosis, and Odonto/Osteogenic Differentiation in Human Dental Pulp Stem Cells.
6-bromoindirubin-3'-oxime (BIO) is a candidate small molecule that effectively modulates Wnt signalling owing to its stable property. The present study investigated the influence of BIO on the odonto/osteogenic differentiation of human dental pulp stem cells (hDPSCs). hDPSCs were treated with 200, 400, or 800 nM BIO, and the effects on hDPSC responses and osteogenic differentiation were assessed. BIO-mediated Wnt activation was confirmed by β-catenin nuclear translocation detected by immunofluorescence staining. BIO attenuated colony formation and cell migration determined by in vitro wound-healing assay. BIO increased early apoptotic cell population evaluated using flow cytometry. For osteogenic induction, BIO promoted alkaline phosphatase (ALP) activity and mineralisation in a dose-dependent manner. ALP, RUNX2, OCN, OSX, ANKH, DMP1, and DSPP mRNA expression were significantly upregulated. The OPG/RANKL expression ratio was also increased. Further, BIO attenuated adipogenic differentiation as demonstrated by decreased lipid accumulation and adipogenic-related gene expression. Bioinformatic analysis of RNA sequencing data from the BIO-treated hDPSCs revealed that BIO modulated pathways related to autophagy and actin cytoskeleton regulation. These findings demonstrated that BIO treatment promoted hDPSC osteogenic differentiation. Therefore, this small molecule is a strong candidate as a bioactive molecule to enhance dentin repair.


Matrix site effects on vibrational frequencies of HXeCCH, HXeBr, and HXeI: a hybrid quantum-classical simulation.
The matrix shifts of the H-Xe stretching frequency of noble-gas hydrides, HXeCCH, HXeBr, and HXeI in various noble-gas matrices (in Ne, Ar, Kr, and Xe matrices) are investigated via the hybrid quantum-classical simulations. The order of the H-Xe stretching frequencies is found to be ν(gas) < ν(Ne) < ν(Xe) < ν(Kr) < ν(Ar) for HXeCCH and HXeBr, while it is ν(gas) < ν(Ne) < ν(Xe) < ν(Ar) < ν(Kr) for HXeI. This order is anomalous with respect to the matrix dielectric constants, and the calculated results reproduce the experimentally observed shifts quite successfully. We also find that the matrix shifts from the gas-phase values are Δν(HXeCCH) ≈ Δν(HXeCl) < Δν(HXeBr) < Δν(HXeI) in the same noble-gas matrix environments, which implies that the weakly bound molecules exhibit large matrix shifts. The local trapping site is analyzed in detail, and it is shown that a realistic modeling of the surrounding matrix environments is essential to describe the unusual matrix shifts accurately.


Modulation of the composition of AP-1 complex and its impact on transcriptional activity.
AP-1 transcription factor known to play a role in cell proliferation and neuronal activation, it is also involved in apoptosis of cells in response to stress, DNA damaging agents or lack of survival signals. AP-1 DNA binding complex is not a single transcription factor but a dimer consisting of members of Fos and Jun families. In this review, we discuss evidence that composition of the AP-1 complex is different under various physiological and pathophysiological conditions. Furthermore, we describe biochemical properties of Fos and Jun proteins that may explain the ability of this transcription factor to activate different sets of genes in response to different stimuli. We propose a hypothesis that AP-1 might contribute to distinct biological processes because an activation of specific signaling pathways results in changes of AP-1 composition and/or phosphorylation status and modulates its transactivating potential towards different promoters.


Mapping the association between mental health and people's perceived and actual ability to practice hygiene-related behaviours in humanitarian and pandemic crises: A scoping review.
Humanitarian crises such as disease outbreaks, conflict and displacement and natural disasters affect millions of people primarily in low- and middle-income countries. Here, they often reside in areas with poor environmental health conditions leading to an increased burden of infectious diseases such as gastrointestinal and respiratory infections. Water, sanitation, and hygiene behaviours are critical to prevent such infections and deaths. A scoping review was conducted to map out what is known about the association between three mental health disorders and people's perceived and actual ability to practice hygiene-related behaviours, particularly handwashing, in humanitarian and pandemic crises. Published and grey literature was identified through database searches, humanitarian-relevant portals, and consultations with key stakeholders in the humanitarian sector. 25 publications were included, 21 were peer-reviewed published articles and four were grey literature publications. Most of the studies were conducted in mainland China (n = 12) and most were conducted in an outbreak setting (n = 20). Six studies found a positive correlation between handwashing and anxiety where participants with higher rates of anxiety were more likely to practice handwashing with soap. Four studies found an inverse relationship where those with higher rates of anxiety were less likely to wash their hands with soap. The review found mixed results for the association between handwashing and depression, with four of the seven studies reporting those with higher rates of depression were less likely to wash their hands, while the remaining studies found that higher depression scores resulted in more handwashing. Mixed results were also found between post-traumatic stress disorder (PTSD) and handwashing. Two studies found that lower scores of PTSD were associated with better hygiene practices, including handwashing with soap. The contradictory patterns suggest that researchers and practitioners need to explore this association further, in a wider range of crises, and need to standardize tools to do so.


Leaf photosynthetic traits scale with hydraulic conductivity and wood density in Panamanian forest canopy trees.
We investigated how water transport capacity, wood density and wood anatomy were related to leaf photosynthetic traits in two lowland forests in Panama. Leaf-specific hydraulic conductivity ( k(L)) of upper branches was positively correlated with maximum rates of net CO(2) assimilation per unit leaf area ( A(area)) and stomatal conductance ( g(s)) across 20 species of canopy trees. Maximum k(L) showed stronger correlation with A(area) than initial k(L) suggesting that allocation to photosynthetic potential is proportional to maximum water transport capacity. Terminal branch k(L) was negatively correlated with A(area)/ g(s) and positively correlated with photosynthesis per unit N, indicating a trade-off of efficient use of water against efficient use of N in photosynthesis as water transport efficiency varied. Specific hydraulic conductivity calculated from xylem anatomical characteristics ( k(theoretical)) was positively related to A(area) and k(L), consistent with relationships among physiological measurements. Branch wood density was negatively correlated with wood water storage at saturation, k(L), A(area), net CO(2) assimilation per unit leaf mass ( A(mass)), and minimum leaf water potential measured on covered leaves, suggesting that wood density constrains physiological function to specific operating ranges. Kinetic and static indices of branch water transport capacity thus exhibit considerable co-ordination with allocation to potential carbon gain. Our results indicate that understanding tree hydraulic architecture provides added insights to comparisons of leaf level measurements among species, and links photosynthetic allocation patterns with branch hydraulic processes.


Effortful information processing in a spontaneous spatial situation by rats with medial prefrontal lesions.
Previous research has suggested that the rat prefrontal cortex might play a role in spatial information processing and in divided attention. More recent work showed that the effect of prefrontal lesions is more important when the task involves response selection in complex situations. The first aim of the present study was to test the effect of lesions of the prelimbic area of the rat prefrontal cortex in spatial exploration, a situation involving the processing of spatial and non-spatial information, but requiring no response selection. The second aim was to manipulate the degree of cognitive effort required by the task. The latter effect was tested by manipulating the number of items to explore. Rats explored either a simple (3 objects) or a complex (6 objects) situation. We reasoned that acquiring spatial information so as to react adequately to spatial or non spatial changes involved more effortful processing in the complex situation than in the simpler one. The results suggest that the medial prefrontal cortex is not crucially involved in effortful processing when the task requires no response selection.


Herpes simplex virus phosphoproteins. II. Characterization of the virion protein kinase and of the polypeptides phosphorylated in the virion.
The protein kinase associated with purified herpes simplex virus 1 and 2 virions partitioned with the capsid-tegument structures and was not solubilized by non-ionic detergents and low, non-inhibitory concentrations of urea. The enzyme required Mg2+ or Mn2+ and utilized ATP or GTP. The activity was enhanced by non-ionic detergents and by Na+ even in the presence of high concentrations of of Mg2+, but not by cyclic nucleotides. The enzyme associated with capsid-tegument structures phosphorylated virion polypeptides only; exogenously added substrates (acidic and basic histones, casein, phosphovitin, protamine, and bovine serum albumin) were not phosphorylated. The major phosphorylated species were virion polypeptides (VP) 1-2, 4, 11-12, 13-14, 18.7, 18.8 and 23. VP 18.7 and VP 18.8 have not been previously detected, but may be phosphorylated forms of polypeptides co-migrating with VP 19. Of the remainder, only VP 23 has been previously identified as a capsid protein; the others are constituents of the tegument or of the under surface of the virion envelope. The distribution of the phosphate bound to viral polypeptides varied depending on the Mg2+ concentration and pH. In the absence of dithiothreitol, in vitro phosphate exchange was demonstrable in VP 23 and to a lesser extent in two other polypeptides on sequential phosphorylation frist with saturating amounts off unlabeled ATP and then with [gamma-32P]ATP. Analysis of the virion polypeptides specified by herpes simplex virus 1 X herpes simplex virus 2 recombinants indicates that the genes specifying the polypeptides which serve as a substrate for the protein kinase map in the unique sequences near the left and right reinterated DNA sequences of the L component.


miR-132 enhances HIV-1 replication.
MicroRNAs upregulated during CD4(+) T cell activation may contribute to the increased efficiency of HIV-1 replication seen following perturbation of the resting state. We have found miR-132 to be highly upregulated following CD4(+) T cell activation, and show that miR-132 potentiates viral replication in the Jurkat CD4(+) T cell line. Knockdown of MeCP2, a previously identified target of miR-132, also increases HIV-1 replication. To the best of our knowledge, miR-132 is the first miRNA reported to enhance HIV-1 replication.


Muscle activity during running in water and on dry land: matched physiology.
We investigated muscle activity during deep water running (DWR) and treadmill running on dry land (TMR) at similar physiological responses. 9 subjects (30.7±10.4 years) participated in this study. The baseline conditions consisted of TMR at 3 ratings of perceived exertion (RPE) level (RPE 11, 13, and 15) with heart rate (HR) recorded during each condition. The target HR for each level of DWR condition was determined by the HR recorded during the TMR. Muscle activity from the rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and gastrocnemius (GA) were measured. As originally planned, HR was not different between modes (P>0.05) and was different between exercise intensities (P<0.001). Only TA muscle activity was influenced by the interaction of mode and intensity (P<0.05). Muscle activity from the GA during DWR was significantly lower than that of TMR (a 34-48% decrease; P<0.05), although muscle activity from the remaining tested muscles were not influenced by modes of exercise (P>0.05). These observations suggest that matching HR can be recommended to produce similar magnitude of lower extremity muscle activity during DWR to that of TMR, with the exception of the GA.


IL-17A produced by γδ T cells promotes tumor growth in hepatocellular carcinoma.
Interleukin (IL)-17A is expressed in the tumor microenvironment where it appears to contribute to tumor development, but its precise role in tumor immunity remains controversial. Here, we report mouse genetic evidence that IL-17A is critical for tumor growth. IL-17A-deficient mice exhibited reduced tumor growth, whereas systemic administration of recombinant mouse IL-17A promoted the growth of hepatocellular carcinoma. The tumor-promoting effect of IL-17A was mediated through suppression of antitumor responses, especially CD8(+) T-cell responses. Furthermore, we found that IL-17A was produced mainly by Vγ4 γδ T cells, insofar as depleting Vγ4 γδ T cells reduced tumor growth, whereas adoptive transfer of Vγ4 γδ T cells promoted tumor growth. Mechanistic investigations showed that IL-17A induced CXCL5 production by tumor cells to enhance the infiltration of myeloid-derived suppressor cells (MDSC) to tumor sites in a CXCL5/CXCR2-dependent manner. IL-17A also promoted the suppressive activity of MDSC to reinforce suppression of tumoral immunity. Moreover, we found that MDSC could induce IL-17A-producing γδ T cells via production of IL-1β and IL-23. Conversely, IL-17A could also enhance production of IL-1β and IL-23 in MDSC as a positive feedback. Together, our results revealed a novel mechanism involving cross-talk among γδ T cells, MDSCs, and tumor cells through IL-17A production. These findings offer new insights into how IL-17A influences tumor immunity, with potential implications for the development of tumor immunotherapy.


Cerebral hemodynamics, vascular reactivity, and metabolism during canine endotoxin shock.
Cerebral hemodynamics, vascular reactivity, and metabolic alterations were studied in anesthetized, spontaneously respiring dogs for 4-6 hr of gram-negative endotoxin shock. Cerebral venous outflow (cerebral blood flow) was measured directly from the cannulated confluence of the sagittal, straight, and lateral sinuses, with the lateral sinuses occluded. Cerebral blood flow and cerebral perfusion pressure decreased immediately upon administration of 1,2, or 5 mg/kg endotoxin and consistently remained below control values. By the fourth hour of shock, cerebral blood flow was decreased 37, 48, and 45% respectively. Cerebral vascular resistance initially decreased, then progressively increased to levels significantly above control, and it was primarily responsible for the reduced cerebral blood flow in the later stages of shock. Cerebral autoregulatory and "venous-arteriolar" responses were well maintained, although cerebral vascular reactivity to arterial hypercapnia was depressed. Cerebral venous blood pH and pO2 decreased, and arterial-venous differences of percentage oxygen saturation, total CO2, and HCO3 increased. These alterations in cerebral vascular hemodynamics and tissue acid-base balance indicate that cerebral ischemia and resulting acidosis occur during canine endotoxin shock.