Genome instability mediates the loss of key traits by Acinetobacter baylyi ADP1 during laboratory evolution.
Acinetobacter baylyi ADP1 has the potential to be a versatile bacterial host for synthetic biology because it is naturally transformable. To examine the genetic reliability of this desirable trait and to understand the potential stability of other engineered capabilities, we propagated ADP1 for 1,000 generations of growth in rich nutrient broth and analyzed the genetic changes that evolved by whole-genome sequencing. Substantially reduced transformability and increased cellular aggregation evolved during the experiment. New insertions of IS1236 transposable elements and IS1236-mediated deletions led to these phenotypes in most cases and were common overall among the selected mutations. We also observed a 49-kb deletion of a prophage region that removed an integration site, which has been used for genome engineering, from every evolved genome. The comparatively low rates of these three classes of mutations in lineages that were propagated with reduced selection for 7,500 generations indicate that they increase ADP1 fitness under common laboratory growth conditions. Our results suggest that eliminating transposable elements and other genetic failure modes that affect key organismal traits is essential for improving the reliability of metabolic engineering and genome editing in undomesticated microbial hosts, such as Acinetobacter baylyi ADP1.


Establishing and Running a Three-dimensional and Advanced Imaging Laboratory.
Multidetector CT technology has advanced during the past 2 decades from single-digit numbers of sections to 320-section CT scanners. The ability to perform three-dimensional (3D) postprocessing of acquired data has accompanied this technical progress. Multiple considerations are involved in developing and deploying a 3D and advanced imaging laboratory to provide postprocessing for both CT and MRI examinations. Establishing and running a 3D laboratory requires administrators to buy into the process and also requires regular input from radiologists and other stakeholders. Technologists with prior 3D experience are rare, and extensive immersive training is typically required. Laboratory space and equipment must be maintained and updated regularly to continue to meet stakeholders' needs. Postprocessing protocols must be established and reviewed periodically. Quality control is also necessary to ensure that postprocessing outputs adhere to the protocols. Laboratory technologists can also provide postprocessing support for research examinations and can lend their technical expertise to research projects. Regular review of laboratory productivity is essential to ensure longevity and availability of necessary resources (human, environmental, and technical). As the technologies for the imaging equipment, the picture archiving and communication system, and postprocessing continue to advance, the role of the 3D laboratory will also evolve to include other services. This evolution will affect ongoing training of technologists, as well as the requirements when new technologists are hired. The 3D laboratory is often positioned to take on novel technology and augment radiologists' workflow as new modalities and techniques enter the clinical workflow. ©RSNA, 2018.


Synthesis and characterization of silyldichloramines, their reactions with F- ions, instability of N2Cl2 and NCl2-, and formation of NCl3.
Only two silyldichloramines, (C6H5)3SiNCl2 and (CH3)3SiNCl2, have been reported in the literature. The synthesis of the former was successfully repeated, and its structure was established by single-crystal X-ray diffraction and vibrational spectroscopy. Attempts to prepare (CH3)3SiNCl2 were unsuccessful; however, a new trialkylsilyldichloramine, t-BuMe2Si-NCl2, was prepared and characterized by Raman and multinuclear NMR spectroscopy. The reaction of t-BuMe2SiNCl2 with (CH3)4NF in CHF3 solution at -78 degrees C, followed by removal of all volatile products at -30 degrees C, produced the expected t-BuMe2SiF byproduct and a white solid consisting of NCl3 absorbed on Me4NCl. The NCl3 could be reversibly desorbed from the substrate and was identified as a neat liquid at room temperature by Raman spectroscopy. The observed final reaction products are consistent with the formation of an unstable N(CH3)4+NCl2- intermediate which decomposes to N(CH3)4+Cl- and NCl molecules which can dimerize to N2Cl2. Theoretical calculations confirm that NCl2- can readily lose Cl- and that N2Cl2 also possesses a low barrier toward loss of N2 to give chlorine atoms and, thus, can account for the formation of NCl3.


An ion displacement membrame model.
The usual assumption in treating the diffusion of ions in an electric field has been that the movement of each ion is independent of the movement of the others. The resulting equation for diffusion by a succession of spontaneous jumps has been well stated by Parlin and Eyring. This paper will consider one simple case in which a different assumption is reasonable. Diffusion of monovalent positive ions is considered as a series of jumps from one fixed negative site to another. The sites are assumed to be full (electrical neutrality). Interaction occurs by the displacement of one ion by another. An ion leaves a site if and only if another ion, not necessarily of the same species, attempts to occupy the same site. Flux ratios and net fluxes are given as functions of the electrical potential, concentration ratios, and number of sites encountered in crossing the membrane. Quantitative comparisons with observations of Hodgkin and Keynes are presented.


MENTAL HEALTH, QUALITY OF LIFE, SPIRITUAL DRYNESS AND ACEDIA SYMPTOMS IN PATIENTS SUFFERING FROM CHRONIC DISEASES.
The aim of the present study is to examine mental health, quality of life, acedia and spiritual dryness in patients suffering from chronic diseases. Materials and method: Data were collected by special design instrument for the needs of the present study. Descriptive statistics and inferential statistics were applied and the analysis was carried out with IBM SPSS 26 and JASP 0.14.01. Results: From the total of 210 participants, 106 (50.4%) were male, the mean age was 62.9 years, and the majority of them were diagnosed with type 2 diabetes. 50 (23.8%) of the participants suffer from anxiety and 39 (18.6%) from depression. In addition, 17.1% experience phases of spiritual dryness frequently or regularly. Physical quality of life component, was associated with the following variables: live from faith, psychological wellbeing, type of disease and age. This model can predict 31.1% of the variance. In terms of psychological wellbeing, the variables living arrangement, awe/gratitude, anxiety, and spiritual dryness can interpret 41.5% of the variance. When it comes to depression, we found that wellbeing, awe/gratitude are predictors of depressive symptoms, explaining at least 14.1% of the variance. Finally, anxiety can be predicted by wellbeing, awe/gratitude, and the type of the disease, interpreting 17.2% of the variance. Conclusions: Patients suffering from chronic diseases are experiencing spiritual dryness and acedia symptoms, and those aspects can be associated with various domains of health and wellbeing.


The cerebellum may implement the appropriate coupling of sensory inputs and motor responses: evidence from vestibular physiology.
Starting from a survey of current ideas on the role of the cerebellum in sensorimotor transformations, the present review summarizes the results of recent experiments showing that (a) somatosensory signals modify the spatial organization of the postural reflexes, thus leading to body stability, and (b) otolith input changes the plane of reflex eye movements, by keeping it perpendicular to the gravito-inertial vector. Evidence will be given that both transformations require the integrity of specific cerebellar regions. These data indicates that the cerebellum allows an optimal input-output coupling in relation to the ultimate behavioural goal of the motor activity.


Deltaran prevents an adverse effect of emotional stress on the course of cerebral ischemia in low-resistant animals.
Local cerebral blood flow in the left hemisphere decreased most significantly in low-resistant Wistar rats preexposed to emotional stress. Deltaran selectively increased blood flow in the left hemisphere and improved blood supply to neuronal activity unit of the brain in these animals. This drug prevented progressive decrease in local cerebral blood flow in both hemispheres during the acute stage of ischemia. The effect of Deltaran was related to modulation of collateral blood flow and adequate blood supply to neuronal activity unit in the brain tissue. Deltaran decreased the mortality rate (by 62%) and alleviated the symptoms of cerebral ischemia. The positive effect of Deltaran was more pronounced in the left hemisphere.


Recovery and partial purification of fibrinolytic protease from Pleurotus ostreatus and P. eryngii and cytotoxic and antioxidant activity of their extracts.
Mushrooms are a source of primary and secondary metabolites. Little is known about the most suitable conditions for production of mushrooms by submerged fermentation. This article reports antioxidant and cytotoxic assays, in addition to quantitatively evaluating the content of proteases with fibrinolytic action in the crude extracts of two species of edible mushrooms produced in different formulations, as well as evaluating the recovery of these enzymes by aqueous two-phase systems (ATPS). The mushrooms Pleurotus ostreatus and Pleurotus eryngii, at concentration of 100 µg/mL, displayed inhibition of DPPH and ABTS radicals below 50%. In the cytotoxicity test, the cells human fibroblast cell lines (MRC-5) showed cell viability greater than 80%. Concerning fibrinolytic activity, P. eryngii presented 226.47 ± 7.26 U/mL, therefore being more efficient than P. ostreatus (71.5 ± 0.56 U/mL). In the recovery of the P. eryngii extract by ATPS, the fibrinolytic protease was partitioned in the salt phase (30.25 U/mL). The molecular mass of the proteases was between 75 and 100 kDa. These results prove the low cytotoxicity of the extracts produced and that fermentation in supplemented malt broth favored the excretion of fibrinolytic proteases compared to the other evaluated media.


Role of Tumor Necrosis Factor-α Inhibitors in the Treatment and Occurrence of Acne: A Systematic Review.
Tumor necrosis factor-α inhibitors (TNFis) approved to treat several inflammatory diseases are sometimes used off label to treat severe forms of acne that are refractory to conventional therapies. However, use of TNFis can also be followed by acne occurrence, suggesting an association between TNFis and acne. Most of the literature on the topic comprises case reports and series that have not been reviewed in a systematic manner. To characterize the demographic characteristics, clinical presentations, treatments, and outcomes of patients receiving TNFis to treat acne and patients who develop acne following treatment of other conditions with TNFis. A systematic literature review was performed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. PubMed and Web of Science were searched from inception through October 17, 2022. Included studies reported on patients of any sex or age who received TNFis whose treatment was followed by resolution or occurrence of acne. Two independent reviewers screened studies based on predefined criteria and extracted data from each study, which were quantitatively combined. A total of 53 studies reporting on 64 patients who received TNFis for the treatment of acne (n = 47) or who experienced acne after treatment with TNFis for a different condition (n = 17) (mean age, 28.7 years; range, 12-64 years; 6 female individuals [8.8%]) were included. The TNFis used included adalimumab, infliximab, and etanercept. Among the 47 patients treated for acne with TNFis, most had previously received antibiotics (31 [66.0%]) or isotretinoin (32 [68.1%]). Most (44 [93.6%]) experienced partial improvement (25 [53.2%]) or clearance (19 [40.4%]) with very few adverse effects reported (3 [6.4%]). Acne manifested as part of an inflammatory syndrome for 30 patients (63.8%). Among the 17 patients treated TNFis for a different condition followed by the occurrence of acne, only 1 patient (5.9%) reported having a history of acne. Therapy with TNFis was either discontinued (8 [47.1%]) or altered (6 [35.3%]) in most patients due to acne occurrence, typically with improvement in symptoms. The results of this systematic review suggest that TNFis can be effective in treating refractory acne but can also be associated with the occurrence of acne in certain instances. Further studies elucidating the role that TNF plays in treating and inducing acne could yield insight into off-label TNFi use and acne pathogenesis, potentially guiding clinical care of patients with acne treated or induced by TNFis.


Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses.
Syntaxin-1 (STX1) and Munc18-1 are two requisite components of synaptic vesicular release machinery, so much so synaptic transmission cannot proceed in their absence. They form a tight complex through two major binding modes: through STX1's N-peptide and through STX1's closed conformation driven by its Habc- domain. However, physiological roles of these two reportedly different binding modes in synapses are still controversial. Here we characterized the roles of STX1's N-peptide, Habc-domain, and open conformation with and without N-peptide deletion using our STX1-null mouse model system and exogenous reintroduction of STX1A mutants. We show, on the contrary to the general view, that the Habc-domain is absolutely required and N-peptide is dispensable for synaptic transmission. However, STX1A's N-peptide plays a regulatory role, particularly in the Ca2+-sensitivity and the short-term plasticity of vesicular release, whereas STX1's open conformation governs the vesicle fusogenicity. Strikingly, we also show neurotransmitter release still proceeds when the two interaction modes between STX1A and Munc18-1 are presumably intervened, necessitating a refinement of the conceptualization of STX1A-Munc18-1 interaction.


[Osteosynthesis of proximal humerus fractures].
Only 5% of adult fractures are fractures of the proximal humerus. In 80% of these fractures one can expect a good result, because they are generally nondisplaced, stable and allow early mobilization. However, the other 20% of these fractures present not only problems with reduction and adequate fixation but also the risk of humeral head necrosis and painful shoulder ankylosis. The operative treatment of displaced fractures of the proximal humerus has changed during the last few years. Minimal osteosynthesis takes into consideration the great extend and the biological aspects of these fractures and provides sufficient stability for early functional therapy. The Neer-classification has proved very useful for both, the indication for and the choice of an operative procedure.


Development, optimization and in vitro evaluation of norcantharidin loadedself-nanoemulsifying drug delivery systems (NCTD-SNEDDS).
This study focused on developing a self-nanoemulsifying drug delivery system (SNEDDS) containing bioactive surfactants under an efficient screening approach for overcoming problems associated with the delivery of norcantharidin (NCTD), a high dose chemotherapy agent having pH dependent solubility. Preliminary screening was implemented to select proper components combination. Besides the solubility of NCTD in the oil phase, emulsifying efficiency, droplet size and size distribution were also employed to select components of the SNEDDS. Moreover, the influence of surfactant and co-surfactant on the interfacial tension and droplets of nanoemulsions were investigated to further understand the mechanism of spontaneous emulsification. Co-surfactant addition promoted the emulsification via reducing the water/oil interfacial tension and viscosity. Ternary phase diagrams were constructed to investigate the phase behavior and designate the optimum systems. The alternative formulations were characterized for cloud point, dilution robustness, droplet size, polydispersity index (PDI) and transmission electron microscopy (TEM). In vitro dissolution study showed that the dissolution rate of optimized formulation (NCTD 10 mg/g, EO 50 wt.%, Cremophor EL 35 wt.%, ethylene glycol 15 wt.%) was slower than drug suspension under the same conditions, confirming that the developed SNEDDS formulation would exhibit sustained release potential.


Measuring knowledge of multiple word meanings in children with English as a first and an additional language and the relationship to reading comprehension.
Polysemy, or the property of words having multiple meanings, is a prevalent feature of vocabulary. In this study we validated a new measure of polysemy knowledge for children with English as an additional language (EAL) and a first language (EL1) and examined the relationship between polysemy knowledge and age, language status, and reading comprehension. Participants were 112 British children aged 5 to 6 (n = 61) or 8 to 9 years (n = 51), 37% of whom had EAL (n = 41). Participants completed the new measure of knowledge of polysemes, along with other measures of language, literacy and cognitive ability. The new measure was reliable and valid with EAL and EL1 children. Age and language status predicted children's polyseme knowledge. Polyseme knowledge uniquely contributed to reading comprehension after controlling for age, language status, non-verbal intelligence, time reading in English, and breadth of vocabulary. This research underscores the importance of polysemy for children's linguistic development.


The Management Script: A Practical Tool for Teaching Management Reasoning.
Management reasoning, a component of clinical reasoning, has become an important area for medical education research given its inherent complexity, role in medical decision making, and association with high-value care. Teaching management reasoning requires characterizing its core concepts and identifying strategies to teach them. In this Perspective, the authors propose the term "management script" to describe the mental schema that clinicians develop and use in medical decision making. Management scripts are high-level, precompiled, conceptual knowledge structures of the courses of action that a clinician may undertake to address a patient's health care problem(s). Like illness scripts, management scripts have foundational elements that are shared by most clinicians but are ultimately idiosyncratic based on each clinician's unique history of learning and experience. Applying management scripts includes 2 steps-(1) management script activation and (2) management option selection-which can occur reflexively (unconsciously) or deliberately (consciously), similar to, respectively, the System 1 thinking and System 2 thinking of dual process theory. Management scripts can be taught for different conditions by using management script templates, educational scaffolds that provide possible courses of action to address a health care problem at any stage. Just as learners use system-based or organ-based frameworks to generate a differential diagnosis, students can use a generic management script template early in training to develop management scripts for specific problems. Future research directions include exploring the role of management scripts in medical education and quality improvement practices.


The use of a standard design medication room to promote medication safety: organizational implications.
Medication administration is one of the most potentially dangerous tasks in hospitals. In recent years, the medical establishment has gained insight into the importance of environmental and ergonomic factors on patient safety. Limited data are available on how a standard designed medication room (MR) supports safety medication administration. Proactive observations were conducted at a tertiary care facility, the Hadassah University Medical Center, Jerusalem, Israel, to determine if safety principles were being implemented in the medication preparation and storage environment. These observations revealed that no designated MRs existed in the hospitals wards and safety systemic weaknesses in medication preparation. Guidelines for planning and designing MRs, based on safety and human engineering principles, were established to promote safer medication administration in hospital wards. The purpose of the survey was to compare the implementation of safety principles among hospital wards before and after MR renovation and among hospital wards with and without a MR. Structured observations in medication preparation areas and storage were designed. Selected safety indicators were measured (e.g. ordering and labeling; storage of intravenous infusions). Each category was subdivided into indicators that were design dependent only (DD), design and behavior dependent (DBD) and behavior dependent only (BD). Indicators that were both DD and DBD showed significant improvement before and after renovation of MRs. Most of the results were not significant for BD indicators. A similar trend was observed in departments with and without a MR. A trend of improvement could be seen in BD-positive indicators, regardless of the presence or absence of a dedicated MR. A standard design MR can improve environmental aspects of safety medication administration.


Part 2: Stabilization/Containment of Radiological Particle Contamination to Enhance First Responder, Early Phase Worker, and Public Safety.
The application of stabilization technologies to a radiologically contaminated surface has the potential for reducing the spread of contamination and, as a result, decreasing worker exposure to radiation. Three stabilization technologies, calcium chloride (CaCl2), flame retardant Phos-Chek® MVP-Fx, and Soil2O™ were investigated to evaluate their ability to reduce the resuspension and tracking of radiological contamination during response activities such as vehicle and foot traffic. Concrete pavers, asphalt pavers, and sandy soil walking paths were used as test surfaces, along with simulated fallout material (SFM) tagged with radiostrontium (Sr-85) applied as the contaminant. Radiological activities were measured using gamma spectrometry before and after simulated vehicle operation and foot traffic experiments, conducted with each stabilization technology and without application as a nonstabilized control. These measurements were acquired separately for each combination of surface and vehicle/foot traffic experiment. The resulting data describes the extent of SFM removed from each surface onto the tires or boots, the extent of SFM transferred to adjacent surfaces, and the residual SFM remaining on the tires or boots after each experiment. The type of surface and response worker actions influenced the stabilization results. For instance, when walked over, less than 2% of particles were removed from nonstabilized concrete, 4% from asphalt, and 40% of the particles were removed from the sand surface. By contrast, for vehicle experiments, ~40% of particles were again removed from the sand, but 7% and 15% from concrete and asphalt, respectively. In most cases, the stabilization technologies did provide improved stabilization. The improvement was related to the type of surface, worker actions, and stabilizer; a statistical analysis of these variables is presented. Overall, the results suggest an ability to utilize these technologies during the planning and implementation of response activities involving foot and vehicle traffic. In addition, resuspension of aerosolizable range SFM was monitored during walking path foot traffic experiments, and all stabilizing agents decreased the measured radioactivity, with the Soil2O™ decrease being 3 fold, whereas the CaCl2 and Phos-Chek MVP-Fx surfaces generated no detectable radioactivity. Overall, these results suggest that the stabilization technologies decrease the availability of particles respirable by response workers under these conditions.


Esophageal obstruction due to enteral feed bezoar: A case report and literature review.
This paper describes a rare complication of enteral feeding, esophageal obstruction due to feeding formula bezoar, and reviews the published cases. An attempt to re-insert the nasogastric tube in a chronically ventilated 80-year-old female fed via a nasogastric tube with Jevity(®) failed. An esophagogastroduodenoscopy revealed an 18 cm-long concretion of the feeding formula, filling most of the esophageal lumen, which was removed endoscopically. Forty-two cases of feeding formula esophageal bezoars have been reported in the literature. The formation of feeding formula bezoars is triggered by acidic gastroesophageal reflux. The acidic pH in the esophagus causes clotting of the casein in the formula. Predisposing factors for bezoar formation are: mechanical ventilation, supine position, neurological diseases, diabetes mellitus, hypothyroidism, obesity and history of partial gastrectomy. Diagnosis and removal of the bezoar is done endoscopically. Feeding in a semi-recumbent position, administration of prokinetic agents and proton pump inhibitors may prevent this complication.


Quality indicators and specifications for the extra-analytical phases in clinical laboratory management.
Quality management systems should cover all the steps involved in the overall testing and non-testing processes. To identify quality indicators for extra-analytical processes in the clinical laboratory and to specify acceptability limits, in order to provide a useful tool for continuous improvement of laboratory service. A literature review by Medline search was performed using the keywords: Q-Tracks and Q-probes alone, and management, error, mistake, and indicator crossed with quality, laboratory and medicine. The indicators retrieved were organized according to the various laboratory processes. Their expression was standardized in relation to the total activity of each process reported in each paper reviewed. The magnitude of the errors reported was considered to be the current state of the art for the extra-analytical step and was proposed as the quality specification. Examples of indicators and specifications for the pre-analytical process: Analytical request: Error in patient identification (0.08%), request unintelligible (0.1%). Requested but not collected (7%), redraws (2%). Transport and reception of samples: Inadequate transportation conditions (0.005%), hemolyzed sample (0.2%). Examples of indicators and specifications for the post-analytical process: Report validation: Test not performed (1.4%), test performed but not requested (1.1%). Intra-laboratory reports: Laboratory reporting errors (0.05%), delivery outside specified time (11%). Consulting service: average time to communicate critical values for inpatients (6 min). These extra-analytical indicators and their specifications, expressed in a standardized manner, constitute a preliminary basis for comparison of individual laboratory performance with the purpose of improving laboratory quality.


IgY antibodies in human nutrition for disease prevention.
Oral administration of preformed specific antibodies is an attractive approach against infections of the digestive system in humans and animals in times of increasing antibiotic resistances. Previous studies showed a positive effect of egg yolk IgY antibodies on bacterial intoxications in animals and humans. Immunization of chickens with specific antigens offers the possibility to create various forms of antibodies. Research shows that orally applied IgY's isolated from egg yolks can passively cure or prevent diseases of the digestive system. The use of these alternative therapeutic drugs provides further advantages: (1) The production of IgY's is a non-invasive alternative to current methods; (2) The keeping of chickens is inexpensive; (3) The animals are easy to handle; (4) It avoids repetitive bleeding of laboratory animals; (5) It is also very cost effective regarding the high IgY concentration within the egg yolk. Novel targets of these antigen specific antibodies are Helicobacter pylori and also molecules involved in signaling pathways in gastric cancer. Furthermore, also dental caries causing bacteria like Streptococcus mutans or opportunistic Pseudomonas aeruginosa in cystic fibrosis patients are possible targets. Therefore, IgY's included in food for human consumption may be able to prevent or cure human diseases.


DSL prescriptive targets for bone conduction devices: adaptation and comparison to clinical fittings.
To develop an algorithm that prescribes targets for bone conduction frequency response shape, compression, and output limiting, along with a clinical method that ensures accurate transforms between assessment and verification stages of the clinical workflow. Technical report of target generation and validation. We recruited 39 adult users of unilateral percutaneous bone conduction hearing aids with a range of unilateral, bilateral, mixed and conductive hearing losses across the sample. The initial algorithm over-prescribed output compared to the user's own settings in the low frequencies, but provided a good match to user settings in the high frequencies. Corrections to the targets were derived and implemented as a low-frequency cut aimed at improving acceptance of the wearer's own voice during device use. The DSL-BCD prescriptive algorithm is compatible with verification of devices and fine-tuning to target for percutaneous bone conduction hearing devices that can be coupled to a skull simulator. Further study is needed to investigate the appropriateness of this prescriptive algorithm for other input levels, and for other clinical populations including those with single-sided deafness, bilateral devices, children and users of transcutaneous bone conduction hearing aids.


Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design.
A tablet formulation based on hydrophilic matrix with a controlled drug release was developed, and the effect of polymer concentrations on the release of primaquine diphosphate was evaluated. To achieve this purpose, a 20-run, four-factor with multiple constraints on the proportions of the components was employed to obtain tablet compositions. Drug release was determined by an in vitro dissolution study in phosphate buffer solution at pH 6.8. The polynomial fitted functions described the behavior of the mixture on simplex coordinate systems to study the effects of each factor (polymer) on tablet characteristics. Based on the response surface methodology, a tablet composition was optimized with the purpose of obtaining a primaquine diphosphate release closer to a zero order kinetic. This formulation released 85.22% of the drug for 8 h and its kinetic was studied regarding to Korsmeyer-Peppas model, (Adj-R(2) = 0.99295) which has confirmed that both diffusion and erosion were related to the mechanism of the drug release. The data from the optimized formulation were very close to the predictions from statistical analysis, demonstrating that mixture experimental design could be used to optimize primaquine diphosphate dissolution from hidroxypropylmethyl cellulose and polyethylene glycol matrix tablets.


Generating Recombinant Avian Herpesvirus Vectors with CRISPR/Cas9 Gene Editing.
Herpesvirus of turkeys (HVT) is an ideal viral vector for the generation of recombinant vaccines against a number of avian diseases, such as avian influenza (AI), Newcastle disease (ND), and infectious bursal disease (IBD), using bacterial artificial chromosome (BAC) mutagenesis or conventional recombination methods. The clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 system has been successfully used in many settings for gene editing, including the manipulation of several large DNA virus genomes. We have developed a rapid and efficient CRISPR/Cas9-mediated genome editing pipeline to generate recombinant HVT. To maximize the potential use of this method, we present here detailed information about the methodology of generating recombinant HVT expressing the VP2 protein of IBDV. The VP2 expression cassette is inserted into the HVT genome via an NHEJ (nonhomologous end-joining)-dependent repair pathway. A green fluorescence protein (GFP) expression cassette is first attached to the insert for easy visualization and then removed via the Cre-LoxP system. This approach offers an efficient way to introduce other viral antigens into the HVT genome for the rapid development of recombinant vaccines.


Increased sequencing depth does not increase captured diversity of arbuscular mycorrhizal fungi.
The arrival of 454 sequencing represented a major breakthrough by allowing deeper sequencing of environmental samples than was possible with existing Sanger approaches. Illumina MiSeq provides a further increase in sequencing depth but shorter read length compared with 454 sequencing. We explored whether Illumina sequencing improves estimates of arbuscular mycorrhizal (AM) fungal richness in plant root samples, compared with 454 sequencing. We identified AM fungi in root samples by sequencing amplicons of the SSU rRNA gene with 454 and Illumina MiSeq paired-end sequencing. In addition, we sequenced metagenomic DNA without prior PCR amplification. Amplicon-based Illumina sequencing yielded two orders of magnitude higher sequencing depth per sample than 454 sequencing. Initial analysis with minimal quality control recorded five times higher AM fungal richness per sample with Illumina sequencing. Additional quality control of Illumina samples, including restriction of the marker region to the most variable amplicon fragment, revealed AM fungal richness values close to those produced by 454 sequencing. Furthermore, AM fungal richness estimates were not correlated with sequencing depth between 300 and 30,000 reads per sample, suggesting that the lower end of this range is sufficient for adequate description of AM fungal communities. By contrast, metagenomic Illumina sequencing yielded very few AM fungal reads and taxa and was dominated by plant DNA, suggesting that AM fungal DNA is present at prohibitively low abundance in colonised root samples. In conclusion, Illumina MiSeq sequencing yielded higher sequencing depth, but similar richness of AM fungi in root samples, compared with 454 sequencing.


Facebook Advertising to Recruit Young, Urban Women into an HIV Prevention Clinical Trial.
Advertising via Facebook to elicit involvement in clinical trials has demonstrated promise in expanding geographic reach while maintaining confidentiality. The purpose of this study is to evaluate Facebook advertising to reach at-risk, predominately African American or Black women in higher HIV prevalence communities for an HIV prevention clinical trial, and to compare baseline characteristics to those recruited on-the-ground. Maintaining confidentiality and the practical aspects of creating and posting ads on Facebook are described. The advertising strategy targeted multicultural affinities, gender, age, interest terms, and zip codes. We report on results during 205 days. A total of 516,498 Facebook users viewed the ads an average of four times, resulting in 37,133 clicks to the study website. Compared to 495 screened on-the-ground, 940 were screened via Facebook ads, of these, half (n = 477, 50.74%) were high risk, and of those at risk, 154 were randomized into the 6-month clinical trial. Black women comprised 71.60% (n = 673) of the total screened online. Roughly twice as many Black women screened via Facebook compared to on-the-ground, yet, the percentage at high risk was similar. Preliminary data suggest that the extent to which ad headlines and photos tap into authentic social experience, advertising on Facebook can extend geographic reach and provide a comparative sample to women recruited on-the-ground.


Sexual behaviour, contraception and fertility among in-school adolescents in Ikenne Local Government, south-western Nigeria.
A cross- sectional study was conducted among in-school adolescents in six secondary schools in the health districts of Ikenne Local Government to assess the sexual behaviour, contraception and fertility experiences of the adolescents between the months of May and November 2002.Relevant information was collected from 1140 in-school adolescents with the aid of pre-tested, structured, self-administered questionnaires, selected by using multistage and stratified random sampling techniques Information sought from the questionnaires included socio-demographic characteristics of the respondents, parental background, their sexual behaviour, knowledge and use of contraception, human development, pregnancy and fertility experiences, information on sexually transmitted infections (STIs) and HIV/AIDS. During the same period, twelve (12) Focus Group Discussions (FGDs) sessions were conducted using an FGD Guide in the selected schools to highlight differences in opinions of students and also to highlight identification of the group consensus. The mean ages at first intercourse were 13.9 +/- 2.8 years and 14.8 +/- 2.4years for males and females respectively. Boys initiated sex earlier than girls. This difference was found to be statistically significant (p<0.05). Sexual intercourse had been experienced by 28.5% of the adolescent students, significantly more (37.6%) males than females (20.4%) The school adolescents that responded as being married were.4.5% (26males, 23 females) of the respondents. Knowledge on contraception was 36.9% and 22.1% for male and female students respectively, more males than females had knowledge of contraception in a significant proportion, apparently due to increase awareness of the male condom among males. Current use of contraception was equally low, and was found to be 10.9% and 6.0% for males and females respectively. The reasons for non-use were mainly that of non-availability (22.3%), cost (11.8%) negative attitude towards contraception due to societal disapproval (33.2%) and lack of knowledge of how to use them (21.3%). The proportion of adolescents that had ever experienced symptoms associated with Sexually Transmitted Infections (STIs) was 26.8%. Multiple factors were found to be responsible for the deplorable reproductive health situation of the adolescents in this community. The need for provision of sexuality and life planning education in schools including the provision of Youth friendly health services in the community were highlighted.


Temporal relationship between instantaneous pressure gradients and peak-to-peak systolic ejection gradient in congenital aortic stenosis.
We sought to identify a time during cardiac ejection when the instantaneous pressure gradient (IPG) correlated best, and near unity, with peak-to-peak systolic ejection gradient (PPSG) in patients with congenital aortic stenosis. Noninvasive echocardiographic measurement of IPG has limited correlation with cardiac catheterization measured PPSG across the spectrum of disease severity of congenital aortic stenosis. A major contributor is the observation that these measures are inherently different with a variable relationship dependent on the degree of stenosis. Hemodynamic data from cardiac catheterizations utilizing simultaneous pressure measurements from the left ventricle (LV) and ascending aorta (AAo) in patients with congenital valvar aortic stenosis was retrospectively reviewed over the past 5 years. The cardiac cycle was standardized for all patients using the percentage of total LV ejection time (ET). Instantaneous gradient at 5% intervals of ET were compared to PPSG using linear regression and Bland-Altman analysis. A total of 22 patients underwent catheterization at a median age of 13.7 years (interquartile range [IQR] 10.3-18.0) and median weight of 51.1 kg (IQR 34.2-71.6). The PPSG was 46.5 ± 12.6 mm Hg (mean ± SD) and correlated suboptimally with the maximum and mean IPG. The midsystolic IPG (occurring at 50% of ET) had the strongest correlation with the PPSG ( PPSG = 0.97(IPG50%)-1.12, R2 = 0.88), while the IPG at 55% of ET was closest to unity ( PPSG = 0.997(IPG55%)-1.17, R2 = 0.87). The commonly measured maximum and mean IPG are suboptimal estimates of the PPSG in congenital aortic stenosis. Using catheter-based data, IPG at 50%-55% of ejection correlates well with PPSG. This may allow for a more accurate estimation of PPSG via noninvasive assessment of IPG.


[Aneurysm of the abdominal aorta. Diagnosis and indications for therapy].
Atherosclerotic abdominal aortic aneurysms are found in about 4% of all men aged over 65 years. The most severe complication of the abdominal aortic aneurysm is rupture. The probability of rupture depends upon the diameter of the aneurysm. The chance of rupture is 30% within 2 years in aneurysms with a maximum diameter of more than 5 cm. Preoperative evaluation includes clinical examination and abdominal ultrasonography. Depending on the results, aortography and/or computed tomography are required. When the diameter is less than 5 cm in an asymptomatic patient, conservative management is indicated provided that clinical tests and ultrasonography are performed on a regular basis. The mean increase of diameter varies between 0.2 and 0.4 cm/year. All aneurysms with a diameter of more than 5 cm should be treated by implantation of a dacron graft. Symptomatic aneurysms should, independently of the diameter, be considered an emergency situation and resected immediately. Patients with ruptured aneurysms have a poor prognosis; only 40-60% of these patients reach the hospital and approximately 50% of them die despite immediate surgery. A special subgroup is the so called inflammatory abdominal aortic aneurysm. Characteristic findings of this entity are increased wall thickness and retroperitoneal fibrosis. The indications for resection are the same as for the atherosclerotic aneurysm. If management is conservative, treatment with corticosteroids is useful.


Antibodies against merokeratin from sheep wool decorate cytokeratin filaments in non-keratinizing epithelial cells.
Merokeratin is an easily soluble proteolytic derivative of mature alpha-keratin. Guinea pig antibodies have been raised to merokeratin prepared from sheep wool. These antibodies decorate in immunofluorescence microscopy arrays of bundles of intermediate sized filaments present in established epithelial cell lines growing in culture. Thus, the highly helical soluble proteolytic fragments of mature alpha-keratin contains antigenic determinants shared by the cytokeratins present in non-epidermal cells, and antibodies to these keratin fragments can be used for the demonstration of at least some cytokeratin-containing structures in other cells and tissues.


Foxb1 Regulates Negatively the Proliferation of Oligodendrocyte Progenitors.
Oligodendrocyte precursor cells (OPC), neurons and astrocytes share a neural progenitor cell (NPC) in the early ventricular zone (VZ) of the embryonic neuroepithelium. Both switch to produce either of the three cell types and the generation of the right number of them undergo complex genetic regulation. The components of these regulatory cascades vary between brain regions giving rise to the unique morphological and functional heterogeneity of this organ. Forkhead b1 (Foxb1) is a transcription factor gene expressed by NPCs in specific regions of the embryonic neuroepithelium. We used the mutant mouse line Foxb1-Cre to analyze the cell types derived from Fobx1-expressing NPCs (the Foxb1 cell lineage) from two restricted regions, the medulla oblongata (MO; hindbrain) and the thalamus (forebrain), of normal and Foxb1-deficient mice. Foxb1 cell lineage derivatives appear as clusters in restricted regions, including the MO (hindbrain) and the thalamus (forebrain). Foxb1-expressing NPCs produce mostly oligodendrocytes (OL), some neurons and few astrocytes. Foxb1-deficient NPCs generate mostly OPC and immature OL to the detriment of neurons, astrocytes and mature OL. The axonal G-ratio however is not changed. We reveal Foxb1 as a novel modulator of neuronal and OL generation in certain restricted CNS regions. Foxb1 biases NPCs towards neuronal generation and inhibits OPC proliferation while promoting their differentiation.


Assessment of the availability of bone volume for grafting in the donor retromolar region using computed tomography: a pilot study.
The purpose of this study was to evaluate the area and volume of bone available for grafting in a donor retromolar region using computed tomography (CT). Ten patients previously scanned by multislice CT were selected for evaluation. Images from partially and completely dentate patients at least 18 years of age were included in the study; those from patients with impacted or erupted third molars or intrabony lesions in the study area were not included. Computer software with appropriate tools was used to handle the images. Two calibrated observers made measurements separately. Safety margins in relation to the lingual cortex, the base of mandible, and the alveolar canal were established in each cross-section of the CTs. Measurements were done by using cross-sectional views, and the results were calculated after three-dimensional reconstruction, providing area and volume data. The mean area of bone available for grafting was 8.12 cm2 (range, 0.00 to 13.60 cm2) and 8.32 cm2 (range, 0.00 to 14.30 cm2) for observers 1 and 2, respectively. Mean available bone volume for grafting was 0.79 cm3 (range, 0.00 to 1.50 cm3) for observer 1 and 0.85 cm3 (range, 0.00 to 1.60 cm3) for observer 2. Interobserver analysis showed substantial agreement. The retromolar region showed a wide variety of anatomic differences among patients. Three-dimensional multislice CT allows reproducible measurements of the area and volume of the retromolar region.


Salvianolic Acid A Has Anti-Osteoarthritis Effect In Vitro and In Vivo.
Osteoarthritis (OA) is a degenerative disease found in middle-aged and elderly people, which seriously affects their quality of life. The anti-inflammatory and anti-apoptosis pharmacological effects of salvianolic acid A (SAA) have been shown in many studies. In this study, we intended to explore the anti-inflammatory and anti-apoptotic effects of SAA in OA. We evaluated the expression of pro-inflammatory mediators and cartilage matrix catabolic enzymes in chondrocytes by ELISA, Griess reaction, immunofluorescence, and Western blot, which includes nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), MMPs (MMP-3, MMP-13), and ADAMTS-5. Bax, Bcl-2, and cleaved caspase-3 were also measured by Western blot methods. The results of this experiment in vitro showed that SAA not only inhibited the production of inflammatory mediators induced by IL-1β and the loss of cartilage matrix but also reduced the apoptosis of mouse chondrocytes induced by IL-1β. According to the results of immunofluorescence and Western blot, SAA inhibited the activation of the NF-κB pathway and MAPK pathway. The results of these in vitro experiments revealed for the first time that SAA down-regulated the production of inflammatory mediators and inhibited the apoptosis of mouse chondrocytes and the degradation of extracellular matrix (ECM), which may be attributed to the inhibition of the activation of NF-κB and MAPK signaling pathways. In the in vivo experiments, 45 mice were randomly divided among three groups (the sham group, OA group, and OA + SAA group). The results of animal experiments showed that SAA treatment for eight consecutive weeks inhibited further deterioration of OA. These results demonstrate that SAA plays an active therapeutic role in the development of OA.


Unilateral pulmonary hypoplasia in an adult patient.
Pulmonary hypoplasia (PH) is a developmental anomaly of the lung parenchyma, characterized by a decrease in the number and size of airways, alveoli and vessels. We present a case of a 31-year-old patient with a history of chronic productive cough and frequent respiratory infections, who was referred for investigation of abnormal chest x-ray. The combination of chest computed tomography (CT) and bronchoscopy set the diagnosis of left pulmonary hypoplasia and the patient was treated surgically with a left pneumonectomy. PH is usually diagnosed immediately after birth, causing severe respiratory failure with high mortality. The less severe, unilateral forms can possibly survive by causing compensatory hyperinflation of the other lung and remain undiagnosed until adulthood, presenting either asymptomatic or with symptoms of chronic bronchitis and recurrent respiratory infections. Chest CT is considered the imaging technique of choice for the diagnosis and for the differential diagnosis from other congenital or acquired conditions. The treatment is usually conservative, although surgical resection is indicated in cases of severe cystic changes and intense symptomatology.


[Stewart-Treves syndrome of the edematous arm following breast cancer operation].
In 1948, Stewart and Treves (158) described a lymphangiosarcoma on the edematous arm for the first time with reference to six cases involving arm edema after breast cancer operation. Since their publication, a further 313 cases have become known. In 1982, with communication of one case we published a statistical compilation comprising of 248 cases (Zeitschrift für Lymphologie VI, 1982, 51-66). A statistical compilation totalling 290 observations is now presented on the basis of further studies of the older literature supplemented by observations of the last six years including two of our own cases. So far, a total of 319 single observations has become known: 21 cases of Yap et al. (182), eight cases of Oshmianskaia et al. (123) and 290 cases in the statistical compilation we have drawn up and which is the basis of this publication. By histological investigation of the tissue material taken from a female patient within six weeks (exploratory excision, radical excision), detailed information could be obtained on the histological development of the Stewart-Treves-Syndrome (STS) from a preneoplasia to a mature lymphangiosarcoma. The second female patient is a relatively rare observation of an STS of fulminant course which remained restricted to the extremity, chest wall and neighboring parts of the back during the entire course.


A Novel Location-Centric IoT-Cloud Based On-Street Car Parking Violation Management System in Smart Cities.
Nowadays, in big cities, parking management is a critical issue from both the driver's side and the city government's side. From the driver's side, how to find an available parking lot in a city is a considerable concern. As a result, smart parking systems recently have received great interest, both in academia and industry. From the city government's side, how to manage and distribute such a limited public parking resource efficiently to give every visitor a fair chance of finding an on-street parking lot is also a considerable concern. However, existing studies of smart parking management focus only on assisting the driver's side to find available parking spaces. This study aims to raise a new perspective on such smart parking management and to propose a novel location-centric IoT-cloud-based parking violation management system. The system is designed to assist authoritative officers in finding parking violations easily and recommends the least cost path for officers so that officers can achieve their highest productivity in finding parking violations and issuing parking tickets. Experimental results show that the system not only improves the productivity of officers in finding parking violations and issuing tickets, but also helps reduce the traveling cost of officers and to reduce the average violation period of violating cars considerably.


Non-neurotoxic activity of Malayan krait (Bungarus candidus) venom from Thailand.
Envenoming by kraits (genus Bungarus) is a medically significant issue in South Asia and Southeast Asia. Malayan krait (Bungarus candidus) venom is known to contain highly potent neurotoxins. In recent years, there have been reports on the non-neurotoxic activities of krait venom that include myotoxicity and nephrotoxicity. However, research on such non-neurotoxicity activities of Malayan krait venom is extremely limited. Thus, the aim of the present study was to determine the myotoxic, cytotoxic and nephrotoxic activities of B. candidus venoms from northeastern (BC-NE) and southern (BC-S) Thailand in experimentally envenomed rats. Rats were administered Malayan krait (BC-NE or BC-S) venom (50 μg/kg, i.m.) or 0.9% NaCl solution (50 μL, i.m.) into the right hind limb. The animals were sacrificed 3, 6 and 24 h after venom administration. The right gastrocnemius muscle and both kidneys were collected for histopathological analysis. Blood samples were also taken for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) levels. The human embryonic kidney cell line (HEK-293) was used in a cell proliferation assay to determine cytotoxic activity. Administration of BC-NE or BC-S venom (50 μg/kg, i.m.) caused time-dependent myotoxicity, characterized by an elevation of CK and LDH levels. Histopathological examination of skeletal muscle displayed marked muscle necrosis and myofiber disintegration 24 h following venom administration. Both Malayan krait venoms also induced extensive renal tubular injury with glomerular and interstitial congestion in rats. BC-NE and BC-S venoms (100-0.2 μg/mL) caused concentration-dependent cytotoxicity on the HEK-293 cell line. However, BC-NE venom (IC50 = 8 ± 1 μg/mL; at 24 h incubation; n = 4) was found to be significantly more cytotoxic than BC-S venom (IC50 = 15 ± 2 μg/mL; at 24 h incubation; n = 4). In addition, the PLA2 activity of BC-NE venom was significantly higher than that of BC-S venom. This study found that Malayan krait venoms from both populations possess myotoxic, cytotoxic and nephrotoxic activities. These findings may aid in clinical diagnosis and treatment of envenomed patients in the future.


N-linked oligosaccharides during human renal organogenesis.
The structure of fucosylated derivatives of N-acetyl lactosamine expressed during human renal development has been studied by the combined use of monoclonal antibodies and glycosyl hydrolases. LeX is expressed on the ureteric bud ampulla carried N-linked on a glycoprotein. It is also present in the proximal tubule as a ganglioside. H-Type II substance is expressed on the endothelium of the developing renal vasculature. It is also carried N-linked to a glycoprotein. These regulated changes in the cell surface carbohydrate expression are important in understanding cell interactions and receptor systems during renal development.


Colorectal cancer screening with nurse-performed flexible sigmoidoscopy: results from a Canadian community-based program.
Despite highest-quality evidence that early detection of colorectal cancer (CRC) can lead to reduced mortality, no organized CRC screening programs exist in Canada. To report the safety, the feasibility, and the detection rate for the first Canadian community-based nurse-performed flexible sigmoidoscopy (FS) screening program for CRC, established in 1999. Cross-sectional analysis of data collected from a prospective study of FS done by nurses from March 1999 to November 2002. Estimate of differences between men and women in FS findings, with relative risks. Logistic regression used to calculate odds ratios for advanced neoplasia. Endoscopy suite of a community hospital. Asymptomatic men and women > or =50 years, with no previous history of CRC. FS done by a nurses, and colonoscopy for persons with abnormalities done by an experienced gastroenterologist. Mean depth of insertion of endoscope; duration of FS procedure; number and location of polyps found during FS; number, location, and type of polyps found during colonoscopy. A total of 1818 individuals (mean age, 62 years) underwent nurse-performed FS (mean duration, 7.3 minutes; mean depth of insertion of the endoscope, 53.5 cm), without complications. Results of the FS were abnormal for 240 (13.2%) of the 1818 participants; 231 (12.7%) underwent colonoscopy. Distal neoplasms (adenomas or cancer) were detected in 8.7% (158/1818). After adjustment for age and family history of CRC, the risk of advanced neoplasm in the distal colon for men was about twice that for women (odds ratio 1.95, 95% confidence interval 1.21-3.14). Cancer was detected in 5 of the 1818 participants screened (0.28%), and high-grade dysplasia was detected in an additional 5 (0.28%). One of the cancers and all the lesions with high-grade dysplasia were treated endoscopically. Our community-based nurse-performed FS screening program was feasible and safe. The referral rate for colonoscopy was 13%, and the cancer detection rate was 2.8 per 1000 persons screened.


An unusual anionic copper(I) cyanide 3D framework encapsulating a cationic copper(II) complex as a guest.
From the reaction of CuICN with conc-NH4OH, a host-guest type 3D network complex , [[CuII(NH3)4(H2O)](H2O)@[CuI3(CN)5]]n was isolated and characterised. A unique cationic complex guest [CuII(NH3)4(H2O)]2+ is encapsulated in the anionic host cage [CuI3(CN)5]2-.


Multicarrier recombination in colloidal quantum dots.
The rates of multicarrier recombination are measured in colloidal quantum dots with and without hole surface trapping and with hole extraction in type II core/shell systems. We report that hole trapping or the physical separation of electronic and hole wavefunctions into different semiconductor domains of a type II system have an insignificant effect on the multicarrier recombination dynamics. These observations are inconsistent with the accepted Auger transition mechanism.


Effects of balance and gait rehabilitation in cerebellar disease of vascular or degenerative origin.
To investigate whether the response to rehabilitation differs between patients with abnormalities of balance and gait due to vascular or to degenerative cerebellar disease. We reviewed the outcome of 27 cerebellar patients. Fourteen patients with vascular and 13 with degenerative cerebellar disease underwent a 3-week inpatient physical therapy program for 5 days/week, 90 min/day, focused on balance and gait. Body sway area during quiet stance with eyes open and eyes closed, and gait velocity, stride length, cadence and step width were recorded. The Berg Balance Scale (BBS) and Functional Independence Measure (FIM) were administered. All tests were performed before and after treatment. Before treatment, both groups showed comparable values in all sway and gait variables and in BBS. FIM score was higher in degenerative than vascular patients. After treatment, a significant reduction of body sway area was observed under both visual conditions in both groups. Gait velocity, stride length and step width improved more in the vascular than in the degenerative patient group. BBS improved in both groups. FIM improved to a larger extent in the vascular patients. Short-term treatment may not be sufficient to produce definite improvement in locomotion in degenerative as much as occurs in vascular patients, even if clinical and functional signs of balance improve in both groups.


Plasma concentrations of gut peptides in dairy cattle increase after calving.
Effects of transition from late gestation to early lactation on plasma concentrations of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1-(7-36) amide (GLP-1), and cholecystokinin (CCK) have not been reported in cattle. The objective of the present study was to measure plasma concentrations of GLP-1, GIP, CCK, insulin, glucose, and nonesterified fatty acids in blood plasma obtained from the coccygeal vein of 32 Holstein cows at an average of 11 d before, and 5, 12, and 19 d after calving. Feed dry matter intake (DMI) averaged 14.4, 17.7, and 19.9 kg/d on d 5, 12, and 19 of lactation, respectively, as milk yield increased (30.6, 36.6, and 39.7 kg/d, respectively). Plasma concentrations of insulin and glucose were lower postpartum than prepartum, but did not differ among samples collected after calving. In contrast, plasma concentration of gut peptides increased linearly after calving, perhaps as a consequence of increased feed intake and nutrient absorption; however, the increases in plasma concentrations of GIP and GLP-1 as lactation progressed were not associated with increased DMI per se, and likely reflect the endocrine and metabolic adaptations of lacto-genesis. In contrast, increased concentration of CCK was related both to increasing days in milk and DMI. By 19 d postpartum, concentrations of GLP-1, GIP, and CCK increased by 2.3-, 1.8-, and 2.8-fold, respectively, compared with values at 11 d before calving. Although these peptides have direct and indirect effects that reduce appetite and DMI in other species (including increased insulin secretion), these may be glucose- or insulin-dependent functions, and insulin and glucose concentrations were reduced in early lactation.


[Cause of death in autopsied RA patients].
A mortality study was performed based on the data of Annual of the Pathological Autopsy Cases in Japan in 1985-1989. The average life span of the RA patients, revealing 66.5 years in male and 64.6 years in female, was shorter than that of general population in Japan. Of 1,246 autopsied RA cases, the most common causes of death were infections (26.6%), respiratory diseases including interstitial lung disease (17.5%) and amyloidosis (12.5%). Amyloidosis was common among RA cases (25.2%), and it was suggested that RA was the most important underlying disorder of the secondary amyloidosis: in 1985 to 1989, 316 cases of 515 secondary amyloidosis (61.4%) were associated with RA.


CaPrx, a Coffea arabica gene encoding a putative class III peroxidase induced by root-knot nematode infection.
Class III peroxidases (Prxs) are enzymes involved in a multitude of physiological and stress-related processes in plants. Here, we report on the characterization of a putative peroxidase-encoding gene from Coffea arabica (CaPrx) that is expressed in early stages of root-knot nematode (RKN) infection. CaPrx showed enhanced expression in coffee roots inoculated with RKN (at 12 h post-inoculation), but no significant difference in expression was observed between susceptible and resistant plants. Assays using transgenic tobacco plants harboring a promoter-β-glucuronidase (GUS) fusion revealed that the CaPrx promoter was exclusively active in the galls induced by RKN. In cross sections of galls, GUS staining was predominantly localized in giant cells. Up-regulation of GUS expression in roots of transgenic plants following RKN inoculation was observed within 16 h. Moreover, no increase in GUS expression after treatment with jasmonic acid was detected. Altogether, these results point to a putative role of this peroxidase in the general coffee response to RKN infection.


The effect of polymer matrices in the in-situ CdS formation under UV irradiation of precursor-polymer films.
Polymer films embedding cadmium thiolate precursors have been irradiated with ultraviolet laser pulses resulting in the formation of cadmium sulfide crystalline nanoparticles through a macroscopically non-destructive procedure for the host matrix. Controlling the number of the incident laser pulses, the gradual increase of the size of the nanoparticles is accomplished, and consequently the progressive change of the emission characteristics of the formed nanocomposites. The X-ray diffraction and transmission electron microscopy measurements were used for the full characterization of the nanoparticles. This study compares two polymer matrices, poly(methyl methacrylate) and a cyclic olefin copolymer, and reveals the importance of each one for the emission characteristics of the formed cadmium sulfide nanocrystals. It is found that the poly(methyl methacrylate) matrix contributes to the increase of the trap states on the surface of the formed nanocrystals, causing the broadening of their emission. On the other hand the cadmium sulfide nanoparticles, grown into the cyclic olefin copolymer matrix, exhibit narrower emission spectra.


Determination of some heavy metals in Mastacembelus mastacembelus (Banks & Solander, 1794) in terms of public health.
In this study, the accumulation of some heavy metals in spiny eel (Mastacembelus mastacembelus Banks and Solander, 1794) living in Karakaya Dam Lake was determined and human health risk of this fish when consumed as food was examined. For this purpose, the amounts of copper (Cu), chromium (Cr), cadmium(Cd), iron (Fe), zinc (Zn) in water samples and in the muscle tissues of the fishes were determined. The amounts of heavy metals showed differences in the muscle tissues of Mastacembelus mastacembelus according to weight, length, sex and age groups of fish. In conclusion the amounts of heavy metals in the flesh of spiny eels were found lower than that recommended by EPA, WHO, FAO and TFC.


Patient safety risks associated with telecare: a systematic review and narrative synthesis of the literature.
Patient safety risk in the homecare context and patient safety risk related to telecare are both emerging research areas. Patient safety issues associated with the use of telecare in homecare services are therefore not clearly understood. It is unclear what the patient safety risks are, how patient safety issues have been investigated, and what research is still needed to provide a comprehensive picture of risks, challenges and potential harm to patients due to the implementation and use of telecare services in the home. Furthermore, it is unclear how training for telecare users has addressed patient safety issues. A systematic review of the literature was conducted to identify patient safety risks associated with telecare use in homecare services and to investigate whether and how these patient safety risks have been addressed in telecare training. Six electronic databases were searched in addition to hand searches of key items, reference tracking and citation tracking. Strict inclusion and exclusion criteria were set. All included items were assessed according to set quality criteria and subjected to a narrative synthesis to organise and synthesize the findings. A human factors systems framework of patient safety was used to frame and analyse the results. 22 items were included in the review. 11 types of patient safety risks associated with telecare use in homecare services emerged. These are in the main related to the nature of homecare tasks and practices, and person-centred characteristics and capabilities, and to a lesser extent, problems with the technology and devices, organisational issues, and environmental factors. Training initiatives related to safe telecare use are not described in the literature. There is a need to better identify and describe patient safety risks related to telecare services to improve understandings of how to avoid and minimize potential harm to patients. This process can be aided by reframing known telecare implementation challenges and user experiences of telecare with the help of a human factors systems approach to patient safety.


Risk Factors in Patients with Low Back Pain Under 40 Years Old: Quantitative Analysis Based on Computed Tomography and Magnetic Resonance Imaging mDIXON-Quant.
While low back pain (LBP) constitutes a global life disorder cause, the contribution of paraspinal muscles to its pathogenicity remains elusive. We characterized the paraspinal muscles of patients with LBP using lumbar three-dimensional computed tomography (CT) and magnetic resonance imaging (MRI) mDIXON-Quant, and evaluated the risk factors combined with clinical data. A retrospective study involving 181 patients (10-40 years) who underwent lumbar 3D-CT and MRI mDIXON from January 1, 2021 to December 31, 2022, and divided into normal, non-chronic LBP [non-CLBP], and CLBP groups. Clinical data, paraspinal muscle cross-sectional area, Hounsfield unit for CT values, and fat fraction derived from mDIXON-Quant were compared. Three readers analyzed the images independently; intra- and interobserver agreement was measured. Spearman analysis and multiple logistic regression were used to analyze the correlation between clinical data, radiologic and paraspinal muscle parameters. A nomogram was constructed for individualized prediction. Correlation analysis revealed that body mass index, visual analog scale score, Pfirrmann grade, annulus fibrosus tear, lumbar lordosis (LL), and Modic changes correlated with LBP (all P<0.05). The Pfirrmann grade and annulus fibrosus tear showed positive correlation (r=0.673, 0.559), whereas LL was negatively correlated (r=-0.469). The multifidus CT values were negatively correlated with LBP at L4-5/L5-S1; the multifidus fat fraction was positively correlated at L4-5/L5-S1 (r=0.734, r=0.584, P<0.001). The multiple logistic regression showed that L4-5 multifidus fat fraction (P=0.046, OR=1.167), Pfirrmann grade (P=0.017, OR=0.063), LL (P=0.002, OR=0.828) and annulus fibrosus tear (P=0.005, OR=0.024) were risk factors for predicting LBP in the non-CLBP group; in the CLBP group, BMI (P=0.048 OR=1.225), L4-5 multifidus fat fraction (P=0.001 OR=1.299), LL (P=0.003, OR=0.841) and Pfirrmann classification (P=0.009, OR=0.046) were risk factors. BMI, L4-5 multifidus fat fraction, LL, and Pfirrmann grade are risk factors for CLBP in patients under 40; whereas annulus fibrosus tear is an independent risk factor for non-CLBP, nomograms derived from these parameters can help predict LBP and MRI mDIXON-Quant is recommended for quantitatively analyzing paraspinal muscle fat infiltration.


Nutritionally enhanced cereals: A sustainable foundation for a balanced diet.
Three nutrients, iron, zinc and pro-vitamin A, are widely deficient in humans, especially among low socioeconomic groups in developing countries, but they remain significant concerns in industrialized countries as well. Cereals provide the majority of the intake of these nutrients in low-income families. Moreover, these three nutrients may interact synergistically in absorption and function to such an extent that there are potentially huge advantages in providing all three together in the one staple food. Because of this, they may be more bioavailable to deficient individuals than current thinking allows. To do so would provide a sound basis on which to build a better balanced diet for nutritionally compromised individuals. Genetic variation in nutrient composition exists in cereals and can be exploited in conventional breeding programmes and through gene technology. Cultural techniques, including fertiliser technology and organic farming, have also impacted upon the nutrient composition of cereals. Human iron and zinc intake can be doubled at least, and essential carotenoid intakes can be increased dramatically. Preliminary feeding trials with nutrient-dense grains have been encouraging. Moreover, nutrient-dense seeds also produce more vigorous seedlings and higher grain yield in soils where these nutrients are poorly available, so that to a significant extent agronomic and health objectives coincide. New varieties are rapidly adopted, especially where there are yield advantages, ensuring maximum impact without new inputs. This approach is potentially more sustainable than fortification and supplementation programmes because intake is continuous, which is especially important for zinc because it is needed almost daily.


Short-Term Effects of a Combined Nutraceutical on Lipid Level, Fatty Liver Biomarkers, Hemodynamic Parameters, and Estimated Cardiovascular Disease Risk: A Double-Blind, Placebo-Controlled Randomized Clinical Trial.
There is a growing interest in nutraceuticals improving cardiovascular risk factor levels and related organ damage. This double-blind, placebo-controlled randomized clinical trial aims to compare the effect of a combined nutraceutical containing red yeast rice (10 mg), phytosterols (800 mg), and L-tyrosol (5 mg) on lipid profile, blood pressure, endothelial function, and arterial stiffness in a group of 60 patients with polygenic hypercholesterolemia resistant to Mediterranean diet. After 8 weeks of treatment, when compared to the placebo group, the active treated patients experienced a more favorable percentage change in total cholesterol (-16.3% vs 9.9%, P < 0.001 always), LDL-C (-23.4% vs -13.2%, P < 0.001 always), and hepatic steatosis index (-2.8%, P < 0.01 vs -1.8%, P < 0.05). Moreover, ALT (-27.7%, P < 0.001), AST (-13.8%, P = 0.004), and serum uric acid (-12.3%, P = 0.005) were reduced by the tested nutraceutical compound both compared to randomization and to placebo, which did not affect these parameters (P < 0.01 for all). Regarding the hemodynamic parameters, there was a decrease of systolic blood pressure (-5.6%) with the active treatment not observed with placebo (P < 0.05 vs baseline and placebo) and endothelial reactivity improved, too (-13.2%, P < 0.001 vs baseline). Consequently, the estimated 10-year cardiovascular risk score improved by 1.19% (SE 0.4%) (P = 0.01) in the nutraceutical-treated patients. The tested nutraceutical association is able to improve the positive effects of a Mediterranean diet on a large number of CV risk factors and consequently of the estimated CV risk. ClinicalTrials.gov identifier NCT02492464. IBSA Farmaceutici.


Synergistic Effect of TPD7 and Berberine against Leukemia Jurkat Cell Growth through Regulating Ephrin-B2 Signaling.
TPD7, a novel biphenyl urea taspine derivative, and berberine have presented inhibition on VEGFR2 that can be regulated by ephrin-B2 reverse signaling through interactions with the PDZ domain. The purpose of this study is to investigate the inhibitory effect of the combination of TPD7 and berberine (TAB) on T-cell acute lymphoblastic leukemia cell growth. TPD7 and berberine together synergistically inhibited the proliferation of Jurkat cells. Also, the combination of TAB induced G1 -phase cell-cycle arrest by downregulating the level of cyclin D1, cyclin E, and CDC2. Furthermore, the combination of TAB significantly enhanced apoptosis in Jurkat cells, and the apoptosis most likely resulted from the modulation of the level of Bcl-2 family members. Most importantly, the concomitant treatment simultaneously regulated the ephrin-B2 and VEGFR2 signaling, as well as modulated the MEK/ERK and PTEN/PI3K/AKT/mTOR signaling. Therefore, the combination treatment of TAB may be a promising therapeutic method in treating T-cell acute lymphoblastic leukemia. Copyright © 2017 John Wiley & Sons, Ltd.


Inhibition of adipose conversion in 3T3-L2 cells by retinoic acid.
The role of retinoic acid in modulating the differentiation of 3T3-L2 fibroblasts into adipocytes has been examined. Results indicate that the retinoid is capable of effectively inhibiting the degree of adipose conversion which is brought about by treatment of preadipocytes with 1-methyl-3-isobutylxanthine plus dexamethasone. MOrphological and enzymatic (fatty acid synthetase activity) expression of the adipose phenotype are both inhibited more than 90% by 10(-6) M retinoic acid. The inhibition is concentration dependent with retinoic acid must be administered simultaneously with the triggering agents to be effective. Exposure of nongrowing preadipocytes to retinoic acid does not alter the ability o the cells to differentiate in response to a subsequent treatment with methylisobutylxanthine plus dexamethasone. Further, the inhibition is reversible. Cultures i which methylisobutylxanthine plus dexamethasone triggered differentiation has been blocked by addition of retinoic acid (10(-6) M) will readily undergo adipose conversion in response to a second treatment with methylisobutylxanthine plus dexamethasone in the absence of the retinoid. Similar inhibition of differentiation was found when cultures were treated with drugs in medium supplemented with either newborn calf serum or fetal calf serum. However, the extent to which methylisobutylxanthine plus dexamethasone are able to promote differentiation in these cells is considerably greater in medium containing fetal calf serum.


A piezoelectric motor using two orthogonal bending modes of a hollow cylinder.
This paper proposes a compact ultrasonic motor with low manufacturing costs, a simpler driving circuit, and scalability. The stator of the motor presented in this paper consists of a hollow metal cylinder, whose outside surface was flattened on two sides at 90 degrees to each other, on which two rectangular piezoelectric plates were bonded. Because the cylinder has a partially square/partially circular outside surface, the stator has two degenerated bending modes that are orthogonal to each other. A wobbling motion is generated on the cylinder when only one piezoelectric plate is excited at a frequency between the two orthogonal bending modes. A rod through a pair of ferrules was used as the rotor of this motor. The prototype motor, whose stator was 2.4 mm in diameter and 10 mm in length, operated at 69.5 kHz, was experimentally characterized, and a maximum torque of 1.8 mNm was obtained.


Separation and purification of sulforaphane from broccoli seeds by solid phase extraction and preparative high-performance liquid chromatography.
A novel, rapid, and economical method to isolate and purify natural sulforaphane from broccoli seeds is described. The procedure involves solvent extraction of autolyzed seed meal, followed by separation by solid phase extraction (SPE) and purification by preparative high-performance liquid chromatography (HPLC). The SPE method provides higher yield of sulforaphane from crude extracts compared to conventional liquid-liquid extraction. High purity and recovery of sulforaphane product can be obtained by preparative HPLC with a C 18 column and 30% methanol in water as the mobile phase. The purified compound was characterized by MS and (1)H and (13)C NMR. The techniques described here are useful tools in the preparative-scale isolation of sulforaphane in a fast, cost-effective, and waste-conscious manner.


Folate-decorated hybrid polymeric nanoparticles for chemically and physically combined paclitaxel loading and targeted delivery.
In this study, folate-functionalized hybrid polymeric nanoparticles (NPs) were prepared as carriers of low water solubility paclitaxel for tumor targeting, which were composed of monomethoxy-poly(ethylene glycol)-b-poly(lactide)-paclitaxel (MPEG-PLA-paclitaxel) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-folate (TPGS-FOL). NPs with various weight ratios of MPEG-PLA-paclitaxel and TPGS-FOL were prepared using a solvent extraction/evaporation method, which can also physically encapsulate paclitaxel. The size, size distribution, surface charge, and morphology of the drug-loaded NPs were characterized using a Zetasizer Nano ZS, scanning electron microscope (SEM), and atomic force microscopy (AFM). The encapsulation and drug loading efficiencies of these polymeric NPs are analyzed using high-performance liquid chromatography (HPLC) at 227 nm. The combination of covalent coupling and physical encapsulation is found to improve the loading of paclitaxel in NPs greatly. The in vitro antitumor activity of the drug-loaded NPs is assessed using a standard method of transcriptional and translational (MTT) assays against HeLa and glioma C6 cells. When the cells were exposed to NPs with the same paclitaxel weights, cell viability decreases in relation to the increase in TPGS-FOL in drug-loaded NPs. To investigate drug-loaded NP cellular uptake, the fluorescent dye coumarin-6 is utilized as a model drug and enveloped in NPs with 0 or 50% TPGS-FOL. Confocal laser scanning microscopy (CLSM) analysis shows that cellular uptake is lower for coumarin-6-loaded NPs with 0% TPGS-FOL than those with 50% TPGS-FOL. However, no difference for NIH 3T3 cells with normally expressed folate receptors is found. Results from in vitro antitumor activity and cellular uptake assay demonstrate that folic acid promotes drug-loaded NP cellular uptake through folate receptor-mediated endocytosis (RME). All of these results demonstrate that folate-decorated hybrid polymeric NPs are potential carriers for tumor-targeted drug delivery.


Preoperative diagnosis of usual leiomyoma, atypical leiomyoma, and leiomyosarcoma.
Uterine smooth muscle tumors (SMTs) are common pelvic tumors in women, and most of them are diagnosed as usual leiomyoma (UL). Exclusion of malignant disease is important in the management of SMTs. However, differentiation of SMTs remains difficult. In this study, we aimed to improve the preoperative diagnosis of SMTs. We examined 21 ULs, 7 atypical leiomyomas (ALs), and 6 leiomyosarcomas (LMSs), all of which were diagnosed by uterine tumor biopsy. Immunohistochemical findings (low-molecular-mass polypeptide 2 (LMP2) and Ki-67) and clinical features (serum lactate dehydrogenase level and menopause) were evaluated. Statistically significant differences in the expression of LMP2 and Ki-67 were observed between UL and AL and between UL and LMS. The combined LMP2 and Ki-67 score was significantly different between UL and AL, between UL and LMS, and between AL and LMS. The combined immunohistochemistry and clinical findings score (total score) was also significantly different between pathological types. The findings of this study suggest that the accuracy of the preoperative diagnosis of SMTs may be improved by using a combination of immunohistochemical and clinical findings.


TRDB--the Tandem Repeats Database.
Tandem repeats in DNA have been under intensive study for many years, first, as a consequence of their usefulness as genomic markers and DNA fingerprints and more recently as their role in human disease and regulatory processes has become apparent. The Tandem Repeats Database (TRDB) is a public repository of information on tandem repeats in genomic DNA. It contains a variety of tools for repeat analysis, including the Tandem Repeats Finder program, query and filtering capabilities, repeat clustering, polymorphism prediction, PCR primer selection, data visualization and data download in a variety of formats. In addition, TRDB serves as a centralized research workbench. It provides user storage space and permits collaborators to privately share their data and analysis. TRDB is available at https://tandem.bu.edu/cgi-bin/trdb/trdb.exe.


[Exercise training for the prevention and treatment of lifestyle-induced diseases].
Diabetes mellitus is one of the major risk factors for coronary artery disease, which progresses in diabetics at a faster rate and is associated with a worse prognosis. Although interventional or surgical revascularization provide quick relief of symptoms for patients with stable coronary artery disease it has limited prognostic benefit. A multi-factorial intervention, which includes dietary measures, glucose and lipid control, anti-hypertensive treatment, and regular physical exercise does exert a positive impact on modifiable risk factors, improves cardiovascular fitness, angina-free exercise tolerance and is associated with a better prognosis. Neither our patients, nor us physicians or even our societies can afford not to include physical exercise into every persons daily life.


Day-to-day reliability of two different models to quantify knee kinematics in subjects with knee osteoarthritis and healthy controls.
Results from instrumented gait analysis vary between test situations. Subject characteristics and the biomechanical model can influence the total amount of variability. The purpose of this study was to quantify reliability of gait data in general, and with respect to the applied model, and investigated population group. Reliability was compared between a functional and a predictive gait model in subjects with knee osteoarthritis and healthy controls. Day-to-day consistency for sagittal plane variables was comparable between models and population groups. Transversal plane variables relative to joint excursion showed larger inconsistency for repeated measures, even for a more sophisticated biomechanical approach. In conclusion, the presented reliability data of sagittal plane kinematics should be used for a reasonable interpretation of results derived in clinical gait analysis. Variables of the transversal plane should not be used as long as sources of error are not sufficiently minimized.


Nigella sativa for the treatment of COVID-19: An open-label randomized controlled clinical trial.
Effective treatment for Coronavirus Disease-2019 (COVID-19) is under intensive research. Nigella sativa oil (NSO) is a herbal medicine with antiviral and immunomodulatory activities, and has been recommended for the treatment of COVID-19. This study aimed to evaluate the efficacy of NSO treatment in patients with COVID-19. All adult patients with mild COVID-19 symptoms presented to King Abdulaziz University Hospital, Jeddah, Saudi Arabia, were recruited for an open label randomized clinical trial (RCT). They were randomly divided into control or treatment groups, with the latter receiving 500 mg NSO (MARNYS® Cuminmar) twice daily for 10 days. Symptoms were daily monitored via telecommunication. The primary outcome focused on the percentage of patients who recovered (symptom-free for 3 days) within 14-days. The trial was registered at clinicaltrials.gov (NCT04401202). A total of 173 patients were enrolled for RCT. The average age was 36(±11) years, and 53 % of patients were males. The control and NSO groups included 87 and 86 patients respectively. The percentage of recovered patients in NSO group (54[62 %]) was significantly higher than that in the control group (31[36 %]; p = 0.001). The mean duration to recovery was also shorter for patients receiving NSO (10.7 ± 3.2 days) compared with the control group (12.3 ± 2.8 days); p = 0.001. NSO supplementation was associated with faster recovery of symptoms than usual care alone for patients with mild COVID-19 infection. These potential therapeutic benefits require further exploration with placebo-controlled, double-blinded studies.


Peptide-tethered monodentate and chelating histidylidene metal complexes: synthesis and application in catalytic hydrosilylation.
The Nδ,Nε-dimethylated histidinium salt (His*) was tethered to oligopeptides and metallated to form Ir(III) and Rh(I) NHC complexes. Peptide-based histidylidene complexes containing only alanine, Ala-Ala-His*-[M] and Ala-Ala-Ala-His*-[M] were synthesised ([M] = Rh(cod)Cl, Ir(Cp*)Cl2), as well as oligopeptide complexes featuring a potentially chelating methionine and tyrosine residue, Met-Ala-Ala-His*-Rh(cod)Cl and Tyr-Ala-Ala-His*-Rh(cod)Cl. Chelation of the methionine-containing histidylidene ligand was induced by halide abstraction from the rhodium centre, while tyrosine remained non-coordinating under identical conditions. High catalytic activities in hydrosilylation were achieved with all peptide-based rhodium complexes. The cationic S(Met),C(His*)-bidentate peptide rhodium catalyst outperformed the monodentate neutral peptide complexes and constitutes one of the most efficient rhodium carbene catalysts for hydrosilylation, providing new opportunities for the use of peptides as N-heterocyclic carbene ligands in catalysis.


Brain natriuretic peptide variations are linked to volume status in hemodialysis patients.
To evaluate the usefulness of monthly brain natriuretic peptide (BNP) dosage in assessing dry weight in hemodialysis patients. Over a 2-year period, we performed in 46 hemodialysis patients monthly BNP level measurements, and adapted dry weight following the determination of variations in BNP concentrations for each month during the study period. Then we tested our approach by looking for a statistical relation between monthly alterations in BNP levels and monthly variations in the patients' weight, blood pressure, hemoglobinemia and albuminemia which are in themselves related to fluid status variations. Monthly BNP level variations were found to be positively correlated with monthly end-dialysis weight alterations (r = +0.24, p < 0.001), with monthly systolic and diastolic blood pressure variations before dialysis (r = +0.09, p < 0.001; r = +0.24, p < 0.001), and with systolic and diastolic blood pressure changes after dialysis (r = +0.09, p = 0.001; r = +0.25, p < 0.001). Moreover, monthly BNP level variations were negatively correlated with monthly hemoglobinemia changes (r = -0.17, p = 0.004) and with monthly albuminemia alterations (r = -0.14, p = 0.001). In a non-selected population of hemodialysis patients it was found that monthly BNP level variations were positively correlated with monthly volume status alterations as evaluated by clinical and biological criteria. BNP appears to be a useful tool for dry weight assessment despite the absence of a standardized cut-off point for BNP levels in hemodialysis patients.


Capillary-force-driven self-assembly of carbon nanotubes: from ab initio calculations to modeling of self-assembly.
In elasto-capillary driven self-assembly of arrays of carbon nanotubes (CNTs) different factors play a role, from the mechanical properties of CNTs to the array geometry. In this work, we provide a multi-scale investigation where we first use density functional theory (DFT) to predict fully ab initio relevant mechanical properties such as Young's modulus, Poisson's ratio, and surface energy. To the best of our knowledge, we are the first to report DFT calculations of the surface energy of CNTs. Then, we feed the computed DFT parameters into a model for capillary-force-driven self-assembly of CNTs. By doing so, we are able to derive and predict cross-correlation between material parameters and array architecture.


Maternal Education Potentially Moderates the MAOA uVNTR Effects on Externalizing Behavior in Black South African Children.
Interactions between the MAOA uVNTR and rearing environment are suggested to influence the developmental manifestations of childhood internalizing and externalizing behavior. However, few studies in the MAOA literature have included continental African children, or focused on non-clinical samples. We explored the main and interactive effects of the MAOA uVNTR (high and low activity alleles) in Black South African male (n = 478) and female (n = 540) children who were part of the longitudinal Birth to Twenty Plus cohort. Historical data on birth weight, gestational age at delivery, socioeconomic status, and maternal education were combined with genotypic information and analyzed using regression modeling. We found no significant main effects for the MAOA uVNTR on childhood behavior in either sex. A significant interaction (p = .04) was identified between MAOA and maternal education, suggesting that externalizing behavior in boys carrying a low activity MAOA allele varied in direct proportion to the education levels of their mothers. However, the model fit failed to reach significance, possibly due to our inclusion of only non-clinical pre-pubertal males. No significant interactions were detected for female children. Our findings lend tentative credibility to the Environmental Sensitivity metaframework, which suggests that MAOA is an important plasticity factor in childhood development.


Role of imaging in allergic rhinology.
Rhinitis is an underestimated clinical condition, which has a considerable impact on the quality of life of the affected patients. The subject of this review focuses on three fundamental aspects: the development of knowledge concerning anatomic landmarks, the development of radiological imaging technology, and developments that can make a difference in the treatment of allergic rhinitis. The anatomical study of paranasal sinuses has been conducted since the time of the ancient Egyptians. Development of radiological equipment from the early 1900s has helped to improve information on the morphology of paranasal sinuses, sufficient to be considered valuable information regarding frontal anatomy and its variability. Imaging has become increasingly important in the diagnosis and treatment of inflammatory diseases of the paranasal sinuses. In recent decades, radiology has helped to study this region as we have progressed from plain radiography to high-resolution Computed Tomography (HRCT). Subsequently, from radiologic imaging, digital volume tomography (DVT) has been developed, in high resolution and narrow section width. Currently, experience with third generation Cone-Beam Computed Tomography (CBCT) technologies provides useful information about bones, and it is now possible to highlight anatomical variants that involve bone structures. We still lack the ability to make a qualitative evaluation of soft tissues, as there are no Hounsfield levels in CBCT. However, this is a new area of research, and its application is evolving in an interesting manner, especially for soft-tissue allergic-inflammatory diseases.


[Environmental responses of four urban tree species transpiration in northern China].
By using thermal dissipation probes (TDP), this paper monitored the sap flow of four tree species (Cedrus deodara, Zelkova schneideriana, Euonymus bungeanus, and Metasequoia glyptostroboides) at the Laodong Park in Dalian City from June to August 2008, and the soil moisture content and micrometeorological variables were mehsured simultaneously. Due to the absence of water-stress in the habitat, the sap flow of all sampled trees had no significant correlation with soil moisture content (R2 < 0.050, P > 0.211, n=1296). The correlation coefficient between solar radiation and sap flow reached 0.624-0.773 (P = 0.00, n=1296) despite the existing hysteresis. Solar radiation had major effect (R2 > 0.700, P < 0.05) during early morning (5:00-8:00) and late afternoon (18:00-20:00) when undergoing dramatic changes. As the main factor determining nighttime sap flow (R2 > 0.660, P < 0.05, n=1872), vapor pressure deficit (VPD) had a correlation coefficient as high as 0.650-0.823 (P = 0.00, n=1296) with the sap flow in whole-day scale. Meanwhile, the models constructed on the basis of VPD were able to explain 90% of daily sap flow change (P = 0.00). The correlation coefficient between sap flow and wind speed was relatively smaller than the previous two (R2 < 0.380, P = 0.00, n=1296), though showing significant correlation in affecting sap flow. Observations also detected the saturation phenomenon of sap flow to the environmental demands.


Rational Design of a Stimuli-Responsive Polymer Electrode Interface Coupled with in Vivo Microdialysis for Measurement of Sialic Acid in Live Mouse Brain in Alzheimer's Disease.
Sensitive and selective monitoring of sialic acid (SA) in cerebral nervous system is of great importance for studying the role that SA plays in the pathological process of Alzheimer's disease (AD). In this work, we first reported an electrochemical biosensor based on a novel stimuli-responsive copolymer for selective and sensitive detection of SA in mouse brain. Notably, through synergetic hydrogen-bonding interactions, the copolymer could translate the recognition of SA into their conformational transition and wettability switch, which facilitated the access and enrichment of redox labels and targets to the electrode surface, thus significantly improving the detection sensitivity with the detection limit down to 0.4 pM. Besides amplified sensing signals, the proposed method exhibited good selectivity toward SA in comparison to potential interference molecules coexisting in the complex brain system due to the combination of high affinity between phenylboronic acid (PBA) and SA and the directional hydrogen-bonding interactions in the copolymer. The electrochemical biosensor with remarkable analytical performance was successfully applied to evaluate the dynamic change of SA level in live mouse brain with AD combined with in vivo midrodialysis. The accurate concentration of SA in different brain regions of live mouse with AD has been reported for the first time, which is beneficial for progressing our understanding of the role that SA plays in physiological and pathological events in the brain.


Grading of MRI-detected skull-base invasion in nasopharyngeal carcinoma with skull-base invasion after intensity-modulated radiotherapy.
The aim of this study is to evaluate the prognostic value of grading MRI-detected skull-base invasion in nasopharyngeal carcinoma (NPC) with skull-base invasion after intensity-modulated radiotherapy (IMRT). This study is a retrospective chart review of 469 non-metastatic NPC patients with skull-base invasion. Patients were classified as extensive skull-base invasion (ESBI) group and limited skull-base invasion (LSBI) group. Multivariate analysis showed that the skull-base invasion (LSBI vs. ESBI) was an independent prognostic predictor of progression free survival (PFS). The estimated 5-year local failure free survival (LFFS), distant metastasis free survival (DMFS), PFS, and overall survival (OS) rates for patients in the T3-LSBI and T3-ESBI group were 92.9% versus 93.5, 89.8% versus 86.1, 81.6% versus 76.4, and 93.5% versus 86.3%, respectively (P > 0.05). Grading of MRI-detected skull-base invasion is an independent prognostic factor of NPC with skull-base invasion. It is scientific and reasonable for skull-base invasion as a single entity to be classified as T3 classification.


Suggestions for the care of patients with liver disease during the Coronavirus 2019 pandemic.
This document, written by the French Association for the Study of the Liver (AFEF) board, aims to provide information to physicians involved in the care of patients with liver disease during the Coronavirus disease (COVID-19) epidemic. These are not based on a systematic review of the literature and a rigorous evaluation using the GRADE method. These are recommendations based on feedback from China available in the form of original articles or letters - for which the scientific evidence is often modest - and the rules put forward by American (1) and European (Boettler et al, 2020) hepatology societies, the French National Digestive Cancer Thesaurus (Di Fiore et al., 2020) and the Francophone Transplantation Society (4). These suggestions require adjustment according to the geographical particularities of the epidemic, available standard procedures and access to local resources. This document will be updated as regularly as possible according to the evolution of our knowledge and characteristics on the epidemic.