Comparison of effects of global cerebral ischaemia on spatial learning in the standard and radial water maze: relationship of hippocampal damage to performance.
Groups of rats which had undergone global ischaemia for 10, 15 or 20 min using the four-vessel occlusion technique were compared with sham-operated controls on learning to locate a submerged platform in both acquisition and working memory tasks in a standard Morris water maze, and in a working memory task in an eight-channel water radial maze. Ischaemic rats showed duration-related impairments in all three tasks. The water radial maze task was learned more slowly than standard water maze tasks, but deficits were long-lasting. In the first phase of training in the radial water maze controls were more reluctant than ischaemic rats to visit all arms of the maze, and were subsequently found to spend less time on the open arms of an elevated plus-maze. However, differences in anxiety are not likely to account for differences in working memory performance in the radial water maze, as groups showed similar error rates before and after habituation to the maze. Histological examination showed that cell loss occurred chiefly in the CA1 field of the hippocampus and was linearly related to duration of occlusion. Cell loss was significantly correlated with the extent of impairment, but the pattern of relationships varied across the different tasks. For water maze acquisition, deficits in latency, heading angle and time spent in the training quadrant related more strongly to CA1 than CA3 cell loss, but radial water maze impairments showed the reverse tendency. In all cases correlations were substantially reduced following exclusion of rats with maximal CA1 cell loss, although a modest relationship with CA1 damage remained for latency in acquisition and working memory tasks, and heading angle on the probe trial. These results suggested that relationships between water maze impairments and cell loss are robust only after near total destruction of the dorsal CA1 field.


A novel split-frequency feature fusion framework for processing the dual-optical images of offshore oil spills.
This paper presents a novel split-frequency feature fusion framework used for processing the dual-optical (infrared-visible) images of offshore oil spills. The self-coding network is used for high-frequency features of oil spill images based on local cross-stage residual dense blocks to achieve feature extraction and construct a regularized fusion strategy. The adaptive weights are designed to increase the proportion of high-frequency features in source images during the low-frequency feature fusion process. A global residual branch is established to reduce the loss of oil spill texture features. The network structure of the primary residual dense block auto-encoding network is optimized based on the local cross-stage method to further reduce the network parameters and improve the network operation speed. To verify the effectiveness of the proposed infrared-visible image fusion algorithm, the BiSeNetV2 algorithm is selected as the oil spill detection algorithm to realize the pixel accuracy of the oil spill image features at 91%.


Distribution and specific central projections of mechanoreceptors in the thorax and proximal leg joints of locusts.
Campaniform sensilla (CS) of the locust proximal leg segments are arranged predominantly as homologous groups on the trochantera and femora. Their number is reduced in the more specialized jumping legs. The specific projections of the primary afferent axons from single groups of CS are visualized after backfilling them with CoCl2 introduced through the dendritic area in the cuticle. The majority of central branching patterns reveal a high degree of uniformity if compared within a population, between populations of one segment, and between populations of different legs. All projections bifurcate close to the peripheral root of the leg nerve and are restricted to the ipsilateral hemiganglion of the segments. These projections seem to differ in their extent more or less from those campaniform sensilla in other parts of the locust and in other insects.


Antimicrobial activity of plant-median synthesized silver nanoparticles against food and agricultural pathogens.
The adjuvant applications of silver nanoparticles (AgNPs) in food and agro-ecosystems are not completely pursued, which most of the researchers confined to laboratory inventions. AgNPs is gaining a lot of interest among worldwide researcher due to exhibit antimicrobial properties and unique physiochemical properties. In addition, the facile and economically friendly method called biological method to synthesis of AgNPs using Bryophyllum pinnatum leaf extract over other methods and including antimicrobial properties, there is no doubt that AgNPs could be twirled the food and agricultural sector in future. The Ag ion reduced to AgNPs within 5 min. The AgNPs had synthesized in pure state of face-centered-cubic nano-crystalline metallic silver with spherical in shape and well dispersed. The AgNPs exhibited against food (Escherichia coli-MTCC-443) and agriculture (Bacillus megaterium-MTCC-2412) pathogens. The synthesized AgNPs are strongly active against microbial associated with food and agriculture pathogens.


Chemostat-induced uneven division of Bacillus subtilis.
Anomalous forms of Bacillus subtilis A32 produced by prolonged cultivation in a chemostat under nitrogen limitation are described. A change in the cultivation conditions brought about a transformation of these forms to bacillar rods. The transformation was gradual and lasted for several generations.


Temporal variation in fixation stiffness affects healing by differential cartilage formation in a rat osteotomy model.
Dynamization involves a reduction in fixation construct stiffness during bone healing, allowing increased interfragmentary movement of the fracture through physiologic weightbearing and muscle contraction. Within some optimal range, interfragmentary movement stimulates healing, but this range likely varies across stages of bone healing. How does the time of dynamization affect the cartilage formation, bony bridging, and bone resorption in a rat fracture-healing model? Unilateral external fixators, stabilizing a 1-mm gap, were dynamized at 1 (D1 group, n = 10), 3 (D3 group, n = 11), or 4 (D4 group, n = 11) weeks postoperatively. Continuously 5 weeks stiff (S group, n = 10) and flexible (F group, n = 11) fixation were included for comparison. After 5 weeks, healing was evaluated by histomorphometric methods. Advanced healing, indicated by less cartilage and a greater rate of bony bridging, was observed in the S group compared to the D1 or F group. In contrast, the D3 and D4 groups had less cartilage and more bridging compared to the S group. Also, the S group had less cortical resorption than the F and D1 groups. These data suggest late dynamization at the onset of bony bridging led to enhanced healing, whereas dynamization at the early stage of cartilage differentiation delayed healing. Although our observations from this small-animal study cannot be directly transferred to humans, these data suggest, once bony bridging begins, dynamization may stimulate bone healing and accelerate remodeling.


Detection of blood group type glycosphingolipid antigens on thin-layer plates using polyclonal antisera.
The conditions for binding of antibodies to glycosphingolipids separated on a thin-layer plate have been optimized for polyclonal antisera. The method has a broad detection range with low background staining. Examples are shown for the detection of blood group A and B active glycosphingolipids.


Comparison of Silodosin Monotherapy vs Silodosin With Tadalafil Add-on Therapy in Patients With Benign Prostatic Hyperplasia.
To evaluate the efficacy and safety of add-on therapy with the phosphodiesterase type 5 inhibitor tadalafil for patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH) treated with the α1-adrenoceptor blocker silodosin. We analyzed 103 patients with LUTS/BPH with an International Prostate Symptom Score (IPSS) of >8 after ≥4 weeks of silodosin treatment from April 2016 through December 2016 at Kori Hospital. The patients subsequently received silodosin 4.0 mg twice daily (monotherapy group) or silodosin 4.0 mg twice daily plus tadalafil 5.0 mg once daily (add-on therapy group) for 8 weeks. We assessed adverse events and evaluated the mean change from baseline to 8 weeks in the IPSS, Overactive Bladder Symptom Score (OABSS), maximum urine flow rate (Qmax), and post-void residual urine volume. Of 103 patients, 101 (98.1%) could continue medical treatment. The IPSS, OABSS, and Qmax showed significantly greater improvement in the add-on therapy than in the monotherapy group (-3.92 vs -1.24, -1.18 vs 0.10, and 1.09 vs -1.04, respectively; all P <.05). Although 4 patients experienced adverse events (add-on therapy: n = 3, 5.7%; monotherapy: n = 1, 2.0%), no significant differences were observed (P = .62). Among patients with overactive bladder (n = 55), the IPSS storage symptom subscore, IPSS urgency subscore, and OABSS urgency subscore showed significantly greater improvement in the add-on therapy than in the monotherapy group (-2.23 vs 0.17, -0.88 vs 0.28, and -1.5 vs -0.48, respectively; all P <.05). Add-on therapy with tadalafil may be effective for patients with LUTS/BPH resistant to silodosin monotherapy.


Orotracheal intubation in the newborn.
One hundred consecutive cases of orotracheal intubation in the premature and term newborn at the Hersehy Medical Center were studied retrospectively. The reason for intubation was for respiratory failure most commonly associated with hyaline membrane disease. The duration of intubation ranged from six hours to 63 days. Seventy-nine percent required intubation for more than 24 hours and 28 percent required intubation for more than one week. No tracheotomies were performed. There were 56 survivors, 50 of which were seen in follow-up examination at three, six or 18-month intervals. There were no cases of clinically evident upper airway damage or obstruction in this group. Post mortem examinations were carried out on 35 infants with tracheal necrosis found in one case. The authors feel that orotracheal intubation is superior to nasotracheal intubation and tracheotomy in this age group. This method of management should be carried out where there is adequate trained personnel and professional staff and equipment capable of proper orotracheal tube placement and management.


Advances in the development paradigm of biosample-based biosensors for early ultrasensitive detection of alzheimer's disease.
This review highlights current developments, challenges, and future directions for the use of invasive and noninvasive biosample-based small biosensors for early diagnosis of Alzheimer's disease (AD) with biomarkers to incite a conceptual idea from a broad number of readers in this field. We provide the most promising concept about biosensors on the basis of detection scale (from femto to micro) using invasive and noninvasive biosamples such as cerebrospinal fluid (CSF), blood, urine, sweat, and tear. It also summarizes sensor types and detailed analyzing techniques for ultrasensitive detection of multiple target biomarkers (i.e., amyloid beta (Aβ) peptide, tau protein, Acetylcholine (Ach), microRNA137, etc.) of AD in terms of detection ranges and limit of detections (LODs). As the most significant disadvantage of CSF and blood-based detection of AD is associated with the invasiveness of sample collection which limits future strategy with home-based early screening of AD, we extensively reviewed the future trend of new noninvasive detection techniques (such as optical screening and bio-imaging process). To overcome the limitation of non-invasive biosamples with low concentrations of AD biomarkers, current efforts to enhance the sensitivity of biosensors and discover new types of biomarkers using non-invasive body fluids are presented. We also introduced future trends facing an infection point in early diagnosis of AD with simultaneous emergence of addressable innovative technologies.


Is bisphosphonate therapy for benign bone disease associated with impaired dental healing? A case-controlled study.
Bisphosphonates are common first line medications used for the management of benign bone disease. One of the most devastating complications associated with bisphosphonate use is osteonecrosis of the jaws which may be related to duration of exposure and hence cumulative dose, dental interventions, medical co-morbidities or in some circumstances with no identifiable aggravating factor. While jaw osteonecrosis is a devastating outcome which is currently difficult to manage, various forms of delayed dental healing may be a less dramatic and, therefore, poorly-recognised complications of bisphosphonate use for the treatment of osteoporosis. It is hypothesised that long-term (more than 1 year's duration) bisphosphonate use for the treatment of post-menopausal osteoporosis or other benign bone disease is associated with impaired dental healing. A case-control study has been chosen to test the hypothesis as the outcome event rate is likely to be very low. A total of 54 cases will be recruited into the study following review of all dental files from oral and maxillofacial surgeons and special needs dentists in Victoria where potential cases of delayed dental healing will be identified. Potential cases will be presented to an independent case adjudication panel to determine if they are definitive delayed dental healing cases. Two hundred and fifteen controls (1:4 cases:controls), matched for age and visit window period, will be selected from those who have attended local community based referring dental practices. The primary outcome will be the incidence of delayed dental healing that occurs either spontaneously or following dental treatment such as extractions, implant placement, or denture use. This study is the largest case-controlled study assessing the link between bisphosphonate use and delayed dental healing in Australia. It will provide invaluable data on the potential link between bisphosphonate use and osteonecrosis of the jaws.


The information imperative: to study the impact of informational discontinuity on clinical decision making among doctors.
Informational discontinuity can have far reaching consequences like medical errors, increased re-hospitalization rates and adverse events among others. Thus the holy grail of seamless informational continuity in healthcare has been an enigma with some nations going the digital way. Digitization in healthcare in India is fast catching up. The current study explores the components of informational continuity, its impact on clinical decision-making and captures the general perception among the doctors towards a digital solution. Cross-sectional study with snowball sampling. A survey questionnaire was developed and validated through a pilot study, then circulated through online platforms. Responses from doctors were obtained through an online Google form for a period of 3 months and analyzed using SPSS 20. The categorical variables were analyzed using Chi-square test. 1413 responses were obtained through a national level survey. Respondents were from a wide range of work experiences, locations, sectors, specialties and patient load. Components of patient records like clinical notes, investigation reports, previous diagnosis and treatment details were rated to be very important. 41% reported about half and 20% reported about 3/4th of their patients do not bring relevant records. Patients from rural areas, visiting state government hospitals and visiting general practitioners were less likely to bring relevant records during consultations. The fallouts of not having timely relevant patient information of the patients include more time per patient, repeat investigations, difficulty to arrive at definitive diagnosis, difficulty to take further treatment decisions and impaired overall clinical decision making which were said to be significant by respondents across the spectrum. The benefits of having timely relevant patient information were also reported consistently across the spectrum. An overwhelming proportion (83%), from across the spectrum, unequivocally expressed their willingness to use digital platforms for accessing patients' relevant medical records. Prevalence of informational discontinuity and its impact on clinical decision making is significant with definite benefits of having timely relevant medical history. There is strong willingness among the doctors to use digital solution(s) without any extra investment or effort on their part making customized solutions pertinent.


Validation of oil fate and mass balance for the Deepwater Horizon oil spill: Evaluation of water column partitioning.
Model predictions of oil transport and fate for the 2010 Deepwater Horizon oil spill (Gulf of Mexico) were compared to field observations and absolute and relative concentrations of oil compounds in samples from 900 to 1400 m depth <11 km from the well. Chemical partitioning analyses using quantitative indices support a bimodal droplet size distribution model for oil released during subsea dispersant applications in June with 74% of the mass in >1 mm droplets that surfaced near the spill site within a few hours, and 1-8% as <0.13 mm microdroplets that remained below 900 m. Analyses focused on 900-1400 m depth <11 km from the well indicate there was substantial biodegradation of dissolved components, some biodegradation in microdroplets, recirculation of weathered microdroplets into the wellhead area, and marine oil snow settling from above 900 m carrying more-weathered particulate oil into the deep plume.


The role of nitrogen in achieving sustainable food systems for healthy diets.
The 'food system' urgently needs a sustainable transformation. Two major challenges have to be solved: the food system has to provide food security with healthy, accessible, affordable, safe and diverse food for all, and it has to do so within the safe operating space of the planetary boundaries, where the pollution from reactive nitrogen turned out to be the largest bottleneck. Here we argue that thinking strategically about how to balance nitrogen flows throughout the food system will make current food systems more resilient and robust. Looking from a material and a governance perspective on the food system, we highlight major nitrogen losses and policy blind spots originating from a compartmentalization of food system spheres. We conclude that a participatory and integrated approach to manage nitrogen flows throughout the food system is necessary to stay within regional and global nitrogen boundaries, and will additionally provide synergies with a sustainable and healthy diet for all.


Self-assembled caseinate-laponite® nanocomposites for curcumin delivery.
In this study, novel self-assembled protein-clay nanocomposites were developed for curcumin delivery. Experimentally, curcumin was dissolved and deprotonated in sodium caseinate-laponite® (NaCas-LAP) dispersion at pH 12.0 for 30 min followed by neutralization to pH = 7. Due to the pH-mediated dissociation and re-association process, curcumin was successfully encapsulated into NaCas-LAP nanocomposites. The colloidal properties and encapsulation capabilities of NaCas-LAP nanocomposites were investigated, including particle size, zeta potential, encapsulation efficiency, release profile in simulated gastrointestinal tract, as well as nanoscale morphology. The results indicated that upon neutralization, NaCas-LAP nanocomposites were re-associated into smaller particles due to strong hydrophobic interactions among NaCas, LAP and curcumin. Specifically, 0.10% curcumin loaded nanocomposites prepared with 2% NaCas and 0.5% LAP showed improved encapsulation performance (73.4%) with smaller particle size (100 nm). The as-prepared protein-clay nanocomposites hold promising potential to deliver lipophilic bioactive compounds, such as curcumin.


Abnormalities in intron retention characterize patients with systemic lupus erythematosus.
Regulation of intron retention (IR), a form of alternative splicing, is a newly recognized checkpoint in gene expression. Since there are numerous abnormalities in gene expression in the prototypic autoimmune disease systemic lupus erythematosus (SLE), we sought to determine whether IR was intact in patients with this disease. We, therefore, studied global gene expression and IR patterns of lymphocytes in SLE patients. We analyzed RNA-seq data from peripheral blood T cell samples from 14 patients suffering from systemic lupus erythematosus (SLE) and 4 healthy controls and a second, independent data set of RNA-seq data from B cells from16 SLE patients and 4 healthy controls. We identified intron retention levels from 26,372 well annotated genes as well as differential gene expression and tested for differences between cases and controls using unbiased hierarchical clustering and principal component analysis. We followed with gene-disease enrichment analysis and gene-ontology enrichment analysis. Finally, we then tested for significant differences in intron retention between cases and controls both globally and with respect to specific genes. Overall decreased IR was found in T cells from one cohort and B cells from another cohort of patients with SLE and was associated with increased expression of numerous genes, including those encoding spliceosome components. Different introns within the same gene displayed both up- and down-regulated retention profiles indicating a complex regulatory mechanism. These results indicate that decreased IR in immune cells is characteristic of patients with active SLE and may contribute to the abnormal expression of specific genes in this autoimmune disease.


Optimization of process conditions with attention to the sludge reduction and stable immobilization in a novel Tubificidae-reactor.
A novel Tubificidae-reactor with special porous carrier and combined aeration system was designed to investigate the sludge reduction. The influences of change in frequency of high-intensity aeration (FHIA), dissolved oxygen (DO) content, initial sludge concentration (ISC) and sludge retention time (SRT) on the immobilization of Tubificidae and sludge reduction were evaluated. Furthermore, response surface method was applied to optimize the process conditions using the sludge reduction rate and stable immobilization of worms as the target parameters to optimize, and DO as the control factors to be optimized with the fluctuation of influent ISC, while keeping FHIA and SRT at optimum level. Attractive sludge reduction rate (470 mg L(-1)d(-1)) can be obtained using the strategies indicated by the highly correlated model. The optimum conditions were found to be DO of 1.0-1.6 mg/L and ISC of 3000-4000 mg/L respectively, while keeping FHIA at 12 times/d and SRT at 2d.


Puffs and salivary gland function: The fine structure of the larval and prepupal salivary glands ofDrosophila melanogaster.
The salivary glands ofDrosophila melanogaster have been examined by electron microscopy for fine structural alterations occurring during larval and prepupal stages. The changes observed in the glands have been correlated with the puffing patterns of the polytene chromosomes at corresponding stages. In early third instar larvae, the lumen of the salivary gland appears empty, and no signs of secretory activity are visible in the glandular cytoplasm. From puff stages 1 to 6 the endoplasmic reticulum becomes reorganized and increases in volume. Electron dense material appears within its cisternae and subsequently within the Golgi saccules. Dense secretory granules then appear to be elaborated from the Golgi by terminal budding; these granules represent the 'glue' for adhering the pupa to its substrate, and gradually increase in size and complexity. By puff stage 6 their contents have been liberated into the glandular lumen. Following puparium formation, those granules which are not extruded coalesce to form larger granules. Other dense bodies and autophagic vacuoles, considered to be lysosomes, appear, and the 'surplus' secretory granules begin to display myelination at their peripheries; ultimately they are reduced to dense residual bodies. At puparium formation, the lumen is depleted of the glue and contains flocculent material. Histolysis commences after puff stage 11, and the cytoplasm becomes vacuolated and opaque; the nucleus becomes reduced in volume and crenated in outline. Nuclear blebbing occurs after puff stage 12, and material seemingly moves from the nucleus into the cytoplasm; the glandular lumen now becomes empty. An attempt has been made to ascertain how the chromosomal puffing activity relates to these cytoplasmic developments.


Variants of the human NRAMP1 gene and susceptibility to tuberculosis in Morocco.
It has been well established that the host genetic background is an important modulator of tuberculosis susceptibility. The NRAMP1 (alias SLC11A1) gene has been associated with tuberculosis susceptibility in several ethnic groups. Here we studied the association and linkage of NRAMP1 with tuberculosis in 116 nuclear families, comprising 211 affected offspring, from Casablanca, Morocco. All enrolled tuberculosis cases were culture-positive. No evidence was found of linkage or association of NRAMP1 with tuberculosis. These findings suggest heterogeneity in the genetic control of tuberculosis susceptibility.


Isotype analysis of the anti-CENP-B anticentromere autoantibody: evidence for restricted clonality.
Utilizing the centromere B fusion protein (CENP-B) and specific, matched monoclonal antiisotype reagents in an enzyme-linked immunosorbent assay, we found that anti-CENP-B autoantibodies were skewed to the IgG1 isotype. The overall kappa:lambda light chain ratio was 2:1, although several individual sera showed a strong predominance of one of the light chains. Isoelectric focusing of light chain-skewed sera showed polyclonal patterns. Our findings are consistent with the anti-CENP-B autoantibody response being a chronic, antigen-driven response.


Lipid droplet evolution gives insight into polyaneuploid cancer cell lipid droplet functions.
Lipid droplets (LDs) are found throughout all phyla across the tree of life. Originating as pure energy stores in the most basic organisms, LDs have evolved to fill various roles as regulators of lipid metabolism, signaling, and trafficking. LDs have been noted in cancer cells and have shown to increase tumor aggressiveness and chemotherapy resistance. A certain transitory state of cancer cell, the polyaneuploid cancer cell (PACC), appears to have higher LD levels than the cancer cell from which they are derived. PACCs are postulated to be the mediators of metastasis and resistance in many different cancers. Utilizing the evolutionarily conserved roles of LDs to protect from cellular lipotoxicity allows PACCs to survive otherwise lethal stressors. By better understanding how LDs have evolved throughout different phyla we will identify opportunities to target LDs in PACCs to increase therapeutic efficiency in cancer cells.


Reduced phase stability and faster formation/dissociation kinetics in confined methane hydrate.
The mechanisms involved in the formation/dissociation of methane hydrate confined at the nanometer scale are unraveled using advanced molecular modeling techniques combined with a mesoscale thermodynamic approach. Using atom-scale simulations probing coexistence upon confinement and free energy calculations, phase stability of confined methane hydrate is shown to be restricted to a narrower temperature and pressure domain than its bulk counterpart. The melting point depression at a given pressure, which is consistent with available experimental data, is shown to be quantitatively described using the Gibbs-Thomson formalism if used with accurate estimates for the pore/liquid and pore/hydrate interfacial tensions. The metastability barrier upon hydrate formation and dissociation is found to decrease upon confinement, therefore providing a molecular-scale picture for the faster kinetics observed in experiments on confined gas hydrates. By considering different formation mechanisms-bulk homogeneous nucleation, external surface nucleation, and confined nucleation within the porosity-we identify a cross-over in the nucleation process; the critical nucleus formed in the pore corresponds either to a hemispherical cap or to a bridge nucleus depending on temperature, contact angle, and pore size. Using the classical nucleation theory, for both mechanisms, the typical induction time is shown to scale with the pore volume to surface ratio and hence the pore size. These findings for the critical nucleus and nucleation rate associated with such complex transitions provide a means to rationalize and predict methane hydrate formation in any porous media from simple thermodynamic data.


Radial vs. Femoral Artery Access for Procedural Success in Diagnostic Cerebral Angiography : A Randomized Clinical Trial.
Radial artery access has become the standard of care in percutaneous coronary procedures due to demonstrated patient safety and comfort benefits; however, uptake of radial access for diagnostic cerebral angiography has been limited by practitioner concerns over the ability to achieve procedural success. We aimed to provide randomized clinical trial evidence for the non-inferiority of radial access to achieve procedural success. Monocentric open label randomized controlled trial with a non-inferiority design and blinded primary outcome assessment. Adult patients referred in-hours for diagnostic cerebral angiography were eligible. Participants underwent permuted block randomization to radial or femoral artery access with an intention-to-treat analysis. The primary outcome was procedural success, defined as selective cannulation and/or diagnostic angiography of predetermined supra-aortic vessels of interest. The non-inferiority limit was 10.0%. Secondary outcomes included postprocedural complications, fluoroscopy and procedural times, radiation dose, contrast volume and rates of vertebral artery cannulation. A total of 80 participants were enrolled (female 42, male 38, mean age 47.0 years, radial access group n = 43, femoral n = 37). One patient in the radial group was excluded after enrollment due to insufficient sonographic radial artery internal diameter. Procedural success was achieved in 41 of 42 participants in the radial group (97.6%) and 36 of 37 in the femoral group (97.3%). The difference between groups was -0.3% (one-sided 95% confidence interval, CI 6.7%) and the null hypothesis was rejected. Radial artery access is non-inferior to femoral artery access for procedural success in cerebral angiography. A large multicenter trial is recommended as the next step.


Acoustic camera system for measuring ultrasound communication in mice.
To investigate biological mechanisms underlying social behaviors and their deficits, social communication via ultrasonic vocalizations (USVs) in mice has received considerable attention as a powerful experimental model. The advances in sound localization technology have facilitated the analysis of vocal interactions between multiple mice. However, existing sound localization systems are built around distributed-microphone arrays, which require a special recording arena and long processing time. Here, we report a novel acoustic camera system, USVCAM, which enables simpler and faster USV localization and assignment. The system comprises recently developed USV segmentation algorithms with a modification for overlapping vocalizations that results in high accuracy. Using USVCAM, we analyzed USV communications in a conventional home cage, and demonstrated novel vocal interactions in female ICR mice under a resident-intruder paradigm. The extended applicability and usability of USVCAM may facilitate future studies investigating typical and atypical vocal communication and social behaviors, as well as the underlying mechanisms.


LncRNA NEAT1 Promotes TLR4 Expression to Regulate Lipopolysaccharide-Induced Trophoblastic Cell Pyroptosis as a Molecular Sponge of miR-302b-3p.
Pyroptosis is an inflammation-triggered cell death caused by certain inflammasomes, and long non-coding RNAs (lncRNAs) are related to cell pyroptosis. This study evaluated the mechanism of lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) on lipopolysaccharide (LPS)-induced trophoblastic cells pyroptosis. HTR-8/Svneo trophoblastic cells were treated with LPS. The expression of lncRNA NEAT1 was decreased using siRNAs, followed by the evaluation of cell proliferation, Caspase-1 activity, levels of Cleaved Caspase-1 and gasdermin D-N, and the concentrations of Interleukin (IL)-1β and IL-18. We found that LPS promoted the pyroptosis of HTR-8/Svneo cells, and lncRNA NEAT1 was highly expressed in LPS-treated HTR-8/Svneo cells while silencing lncRNA NEAT1 inhibited LPS-induced trophoblastic cells pyroptosis. The subcellular localization of lncRNA NEAT1 was detected. Dual-luciferase gene experiment and RNA pull-down assay detected that lncRNA NEAT1 bound to miR-302b-3p and could inhibit miR-302b-3p, and toll-like receptor 4 (TLR4) was the target gene of miR-302b-3p. Then, a joint experiment was designed for detection, which found that miR-302b-3p downregulation partially reversed the inhibition of silencing lncRNA NEAT1 on LPS-induced trophoblastic cells pyroptosis and overexpression of TLR4 annulled the inhibition of silencing lncRNA NEAT1 on LPS-induced trophoblastic cells pyroptosis. Therefore, lncRNA NEAT1 promoted the transcription of TLR4 by competitively binding to miR-302b-3p, thus promoting LPS-induced trophoblastic cells pyroptosis.


Air-water interfacial behaviour of whey protein and rapeseed oleosome mixtures.
Plant seeds store lipids in oleosomes, which are storage organelles with a triacylglycerol (TAG) core surrounded by a phospholipid monolayer and proteins. Due to their membrane components, oleosomes have an affinity for the air/oil-water interface. Therefore, it is expected that oleosomes can stabilise interfaces, and also compete with proteins for the air-water interface. We mixed rapeseed oleosomes with whey protein isolate (WPI), and evaluated their air-water interfacial properties by interfacial rheology and microstructure imaging. To understand the contribution of the oleosome components to the interfacial properties, oleosome membrane components (phospholipids and membrane proteins) or rapeseed lecithin (phospholipids) were also mixed with WPI. Oleosomes were found to disrupt after adsorption, and formed TAG/phospholipid-rich regions with membrane fragments at the interface, forming a weak and mobile interfacial layer. Mixing oleosomes with WPI resulted in an interface with TAG/phospholipid-rich regions surrounded by whey protein clusters. Membrane components or lecithin mixed with proteins also resulted in an interface where WPI molecules aggregated into small WPI domains, surrounded by a continuous phase of membrane components or phospholipids. We also observed an increase in stiffness of the interfacial layer, due to the presence of oleosome membrane proteins at the interface.


A new situation awareness model decreases clinical deterioration in the emergency departments-A controlled intervention study.
Studies have suggested that adding subjective parameters to early warning score (EWS) systems might prompt more proactive treatment and positively affect clinical outcomes. Hence, the study aimed to investigate effect of a situation awareness model consisting of objective and subjective parameters on clinical deterioration in adult emergency department (ED) patients. This controlled pre-and-post interventional study was carried out in July-December 2016 and November 2017-April 2018. In ED patients ≥ 18 years, we examined if a situation awareness model compared with a conventional EWS system could reduce clinical deterioration. The new model consisted of a regional EWS, combined with skin observation, clinical concern and patients' and relatives' concerns, pain, dyspnea, and team risk assessment. Clinical deterioration was defined as change in vital signs requiring increased observation or physician assessment, that is, increase in early warning score from either 0 or 1 to score ≥2 or an increase from score ≥2 and above. Secondary outcomes were mortality, intensive care unit (ICU) admissions, and readmissions. We included 34 556 patients. Patients with two or more registered EWS were included in the primary analysis (N = 21 839). Using difference-in-difference regression, we found a reduced odds of clinical deterioration of 21% (OR 0.79 95% CI [0.69; 0.90]) in the intervention groups compared with controls. No impact on mortality, ICU, or readmissions was found. The situation awareness model reduces odds of clinical deterioration, defined as a clinically relevant increase in EWS, in an unselected adult population of ED patients. However, there was no effect on secondary outcomes.


An overview of heat stress in tomato (Solanum lycopersicum L.).
Heat stress has been defined as the rise of temperature for a period of time higher than a threshold level, thereby permanently affecting the plant growth and development. Day or night temperature is considered as the major limiting factor for plant growth. Earlier studies reported that night temperature is an important factor in the heat reaction of the plants. Tomato cultivars capable of setting viable fruits under night temperatures above 21 °C are considered as heat-tolerant cultivars. The development of breeding objectives is generally summarized in four points: (a) cultivars with higher yield, (b) disease resistant varieties in the 1970s, (c) long shelf-life in 1980s, and (d) nutritive and taste quality during 1990s. Some unique varieties like the dwarf "Micro-Tom", and the first transgenic tomato (FlavrSavr) were developed through breeding; they were distributed late in the 1980s. High temperature significantly affects seed, pollen viability and root expansion. Researchers have employed different parameters to evaluate the tolerance to heat stress, including membrane thermo stability, floral characteristics (Stigma exertion and antheridia cone splitting), flower number, and fruit yield per plant. Reports on pollen viability and fruit set/plant under heat stress by comparing the pollen growth and tube development in heat-treated and non-heat-stressed conditions are available in literature. The electrical conductivity (EC) have been used to evaluate the tolerance of some tomato cultivars in vitro under heat stress conditions as an indication of cell damage due to electrolyte leakage; they classified the cultivars into three groups: (a) heat tolerant, (b) moderately heat tolerant, and (c) heat sensitive. It is important to determine the range in genetic diversity for heat tolerance in tomatoes. Heat stress experiments under field conditions offer breeders information to identify the potentially heat tolerant germplasm.


Rho kinase-related proteins in human vaginal arteries: an immunohistochemical and functional study.
The calcium-sensitizing Rho A/Rho kinase pathway has been suggested to play a role in the control of nongenital vascular smooth muscle. Rho-associated kinases (ROKs) cause calcium-independent modulation of smooth muscle contraction, and have been demonstrated in the bladder, prostate, and corpus cavernosum. Until now, it is not known whether ROKs and related proteins play a role in the control of vaginal blood flow. To investigate by means of functional studies and immunohistochemistry the significance of the Rho pathway in human vaginal arteries. Vaginal tissue was obtained from five postmenopausal women. Specimens were processed for immunohistochemistry for ROK1, ROK2, RhoA, and RhoGDI. Segments of sub-epithelial vaginal arteries were mounted in a tissue bath. Effects of Y27632 on the concentration-response curves to phenylephrine (Phe) or Phe-precontracted preparations were investigated. The expression of Rho kinases ROK1, ROK2, and the Rho-associated protein RhoGDI in human vaginal arteries was investigated by means of immunohistochemistry. Tissue bath studies were conducted in order to characterize the effects of the ROK inhibitor Y27632 on isolated vaginal arteries. A meshwork of α-actin immunoreactive arterioles was located in the sub-epithelium of human vaginal specimens. Immunoreactivities for ROK1, ROK2, RhoA, and RhoGDI were expressed in the smooth musculature of these arteries. At 0.1 and 1 µM Y27632, the contraction to Phe (10 µM) was 99 ± 17% and 28 ± 12% that of 124 mM K(+) . In Phe-contracted preparations, Y27632 produced relaxant responses. The activation of alpha(1) -adrenoceptors contracts sub-epithelial human vaginal arteries via ROK-sensitive mechanisms. A role for these signals in the regulation of vaginal blood flow might be considered.


Associations between tryptophan and iron metabolism observed in individuals with and without iron deficiency.
Current literature proposes associations between tryptophan metabolism and anaemia. However, study cohorts are rather small and final conclusions are still lacking. Here, we evaluated potential associations of tryptophan, kynurenine, and kynurenic acid with indicators of iron metabolism (i.e., mean corpuscular volume, mean corpuscular haemoglobin, ferritin, transferrin saturation, serum iron, transferrin, soluble transferrin receptor, reticulocyte haemoglobin) and haemoglobin in 430 individuals grouped by the presence or absence of iron deficiency or anaemia. Indicators of tryptophan metabolism were positively correlated with haemoglobin and markers of iron metabolism (p-values: <0.001-0.038; r-values: 0.100-0.305). The strongest correlation was observed between tryptophan and haemoglobin (p < 0.001, r = 0.305). The cubic regression model yielded the highest R-square values between haemoglobin and tryptophan markers. Overall, 115 patients with iron deficiency showed lower tryptophan and kynurenic acid concentrations compared to 315 individuals without iron deficiency. Six patients with anaemia of chronic disease were observed with the lowest serum tryptophan levels and the highest kynurenine/tryptophan ratio compared to 11 individuals with iron deficiency anaemia and 413 non-anaemic patients. This study showed little/moderate associations between haemoglobin, biomarkers of iron metabolism and tryptophan markers. Further studies are needed to get better insight in the causality of these findings.


The effects of route of admission to a percutaneous coronary intervention centre among patients with out-of-hospital cardiac arrest.
Patients with OHCA who are not transported directly to a percutaneous coronary intervention (PCI)-capable hospital may eventually undergo an inter-hospital transfer (IHT). The aim of the present study was to investigate the effects of route of admission to a PCI centre among patients with OHCA. We included patients with OHCA of presumed cardiac aetiology that were admitted to a PCI centre between January 2015 and December 2016. The exposure variable was route of admission: direct versus indirect. The 'direct' group was defined as patients who were transferred directly from the field to a PCI centre by emergency medical service (EMS) providers. The 'indirect' group was defined as patients who underwent IHT from a non-PCI centre to a PCI centre. The primary outcome was neurological recovery. We evaluated the effects of route of admission using multivariable logistic regression analysis after adjusting for potential confounders. There were total of 4363 eligible patients: 3488 (78.2%) in the direct group and 975 (21.8%) in the indirect group. Neurologic recovery was better in the direct group (38.0%) than in the indirect group (29.0%). After adjusting for potential confounders, indirect admission was negatively associated with outcomes (adjusted odds ratio [aOR] 0.70; 95% confidence interval [CI] 0.58-0.85). The route of admission to a PCI centre is associated with neurological recovery among resuscitated patients with OHCA of presumed cardiac aetiology. This has implications for regionalized EMS transport and IHT protocols for patients with OHCA.


Implication of lipid peroxides in gastric ulcer formation in indomethacin-treated rats.
With the carrageenin food oedema assay, we studied in rats the effects of indomethacin on inflammation, gastric ulcers and lipid peroxide levels. Our results show a positive correlation between ulceration and plasma lipid peroxides. We suggest that the ulceration could be due to inhibition of prostacyclin synthetase by lipid peroxides.


Interferon ε restricts Zika virus infection in the female reproductive tract.
Interferon ε (IFNε) is a unique type I IFN that has been implicated in host defense against sexually transmitted infections (STIs). Zika virus (ZIKV), an emerging pathogen, can infect the female reproductive tract (FRT) and cause devastating diseases, particularly in pregnant women. How IFNε contributes to protection against ZIKV infection in vivo is unknown. Here, we show that IFNε plays a critical role in host protection against vaginal ZIKV infection in mice. We found that IFNε was expressed not only by epithelial cells in the FRT, but also by certain immune and other cells at baseline or after exposure to viruses or specific TLR agonists. IFNε-deficient mice exhibited abnormalities in the epithelial border and underlying tissue in the cervicovaginal tract, and these defects were associated with increased susceptibility to vaginal, but not subcutaneous ZIKV infection. IFNε-deficiency resulted in an increase in magnitude, duration, and depth of ZIKV infection in the FRT. Critically, intravaginal administration of recombinant IFNε protected Ifnε-/- mice and highly susceptible Ifnar1-/- mice against vaginal ZIKV infection, indicating that IFNε was sufficient to provide protection even in the absence of signals from other type I IFNs and in an IFNAR1-independent manner. Our findings reveal a potentially critical role for IFNε in mediating protection against transmission of ZIKV in the context of sexual contact.


Genetic analyses of Chinese isolates of Toxoplasma gondii reveal a new genotype with high virulence to murine hosts.
A great deal of evidence demonstrates that a strongly clonal population structure of Toxoplasma gondii strains exists in humans and animals in North America and Europe, while the strains from South America are genetically separate and more diverse. Potential differences in virulence between different strains mean that an understanding of strain diversity is important to human and animal health. However, to date, only one predominant genotype, ToxoDB#9 (Chinese I), and a few other genotypes, including ToxoDB#205, have been identified in China. By using DNA sequence-based phylogenetic analyses, we have re-evaluated the population structure of T. gondii strains collected from China and compared them with other global strains. Based on phylogenetic analysis of restriction fragment length polymorphisms, multilocus sequence typing and intron sequences from T. gondii, we propose that the Chinese isolates described as Chinese I are divided into two groups called Chinese I and Chinese III. Our results demonstrate that significant differences were found in mouse mortality caused by some Chinese strains, and also the archetypal I, II, III strains in mice. Furthermore, a comparison of cyst loading in the brains of infected rats showed some Chinese strains to be capable of a high degree of cyst formation. Furthermore we show that genotyping using neutral genetic markers may not be a useful predictor of pathogenic phenotypes.


The efficiency of strict reverse isolation and antimicrobial decontamination in remission induction therapy of acute leukemia.
The efficiency of strict reverse isolation and antimicrobial decontamination in remission induction therapy of acute leukemia was studied retrospectively in 47 patients who were treated with a standardized aggressive chemotherapy of daunorubicin and cytosine arabinoside. Twenty-two patients were treated in strict reverse isolation with antimicrobial decontamination and 25 patients in the open ward without any measures against infections. In the patients in isolation the incidence of new infections per patient was 0.77 compared to 1.42 in the control group. The rate of complete remissions was 77% in the patients in isolation vs. 56% in the control patients.


Novel Chlamydiae and Amoebophilus endosymbionts are prevalent in wild isolates of the model social amoeba Dictyostelium discoideum.
Amoebae interact with bacteria in multifaceted ways. Amoeba predation can serve as a selective pressure for the development of bacterial virulence traits. Bacteria may also adapt to life inside amoebae, resulting in symbiotic relationships. Indeed, particular lineages of obligate bacterial endosymbionts have been found in different amoebae. Here, we screened an extensive collection of Dictyostelium discoideum wild isolates for the presence of these bacterial symbionts using endosymbiont specific PCR primers. We find that these symbionts are surprisingly common, identified in 42% of screened isolates (N = 730). Members of the Chlamydiae phylum are particularly prevalent, occurring in 27% of the amoeba isolated. They are novel and phylogenetically distinct from other Chlamydiae. We also found Amoebophilus symbionts in 8% of screened isolates (N = 730). Antibiotic-cured amoebae behave similarly to their Chlamydiae or Amoebophilus-infected counterparts, suggesting that these endosymbionts do not significantly impact host fitness, at least in the laboratory. We found several natural isolates were co-infected with multiple endosymbionts, with no obvious fitness effect of co-infection under laboratory conditions. The high prevalence and novelty of amoeba endosymbiont clades in the model organism D. discoideum opens the door to future research on the significance and mechanisms of amoeba-symbiont interactions.


Sustainability evaluation of the use of cargo-trams for mixed municipal waste transport in Prague.
The use of trams for the transport of waste from urban areas to waste incineration facilities - does it make sense, would it be technically feasible, economically sustainable and environmentally beneficial? These are the questions which we attempted to answer in this comprehensive study. The analysis is performed for a specific potential implementation of this system in Prague and adjacent municipalities. In this work, we compare the current state, where mixed municipal waste is transported to an incineration plant directly by garbage trucks, with variants if mixed municipal waste were taken to transfer stations and from there transported over a longer distance in a large volume by means of tram or truck. Our results show that use of trams results in an overall cost level of €16.41 per ton of waste transported, which represents a slight saving against the existing system at a cost of €17.19 per ton. From the purely economic perspective, however, this does not compete with transportation by truck at €12.28 per ton - above all due to high initial investment into new cargo trams. From the environmental viewpoint, deploying trams brings benefits largely on the local level, where emissions would be reduced by about 50% against the current state. In the global view, assessed through the Life Cycle Assessment method, it appears however only to transfer emissions to the point of energy production, and from this perspective the use of trams is beneficial only if linked with a notable shift from fossil fuel energy to nuclear or renewable sources.


Baseline heavy metals and metalloid values in blood of loggerhead turtles (Caretta caretta) from Baja California Sur, Mexico.
Environmental pollution due to heavy metals is having an increased impact on marine wildlife accentuated by anthropogenic changes in the planet including overfishing, agricultural runoff and marine emerging infectious diseases. Sea turtles are considered sentinels of ecological health in marine ecosystems. The objective of this study was to determine baseline concentrations of zinc, cadmium, copper, nickel, selenium, manganese, mercury and lead in blood of 22 clinically healthy, loggerhead turtles (Caretta caretta), captured for several reasons in Puerto López Mateos, Baja California Sur, Mexico. Zinc was the most prevalent metal in blood (41.89 μg g⁻¹), followed by Selenium (10.92 μg g⁻¹). The mean concentration of toxic metal Cadmium was 6.12 μg g⁻¹ and 1.01μg g⁻¹ respectively. Mean concentrations of metals followed this pattern: Zn>Se>Ni>Cu>Mn>Cd>Pb and Hg. We can conclude that blood is an excellent tissue to measure in relatively non-invasive way baseline values of heavy metals in Caretta caretta.


Thymostimulin increases natural cytotoxic activity in patients with breast cancer.
The effect of thymostimulin on the Natural Killer (NK) cytotoxic activity of peripheral blood mononuclear cells (PBMC) was investigated in 15 patients with breast cancer after finishing or during chemotherapy (CAF) and in 10 healthy controls. PBMC from these subjects were incubated in the presence of thymostimulin for varying periods of time (18 h or 5 days), and then used as effector cells against 51Cr-radiolabeled NK-sensitive (K-562) and NK-resistant (JY) target cells in cytotoxicity assays. No significant differences were observed between the NK-activity from breast cancer patients and healthy controls. Thymostimulin induced a dose- and time-dependent cytotoxic enhancing effect on the cytotoxic activity of PBMC from these patients against NK-sensitive K562 target cells. The thymostimulin (1000 ng/ml) significantly enhanced cytotoxic activity in PBMC from breast cancer patients who had previously received chemotherapy (p = 0.0277) against NK-sensitive cells. This increase was not statistically significant neither in PBMC from patients receiving chemotherapy nor in healthy controls (p > 0.05 in both cases). The incubation of PBMC from patients with breast cancer was not associated to a significant enhancement of the cytotoxic activity against NK-resistant target cells (p > 0.05). We also found that thymostimulin could synergize with interleukin-2 in inducing NK cytotoxic activity in PBMC after 18 h of culture (p = 0.0277). In conclusion, we have demonstrated that thymostimulin enhances the natural killer cytotoxic activity of PBMC from patients with breast cancer who have previously received chemotherapy.


Dipeptide formation with misacylated tRNAPhes.
Several misacylated P-site tRNAs have been prepared by the T4 RNA ligase-mediated coupling of Escherichia coli tRNAPhe missing the 3'-terminal cytidine and adenosine moieties and N-acetylaminoacyl-pCpA derivatives. The reaction proceeded in reasonable yield in each case and the tRNA products were purified conveniently by successive chromatographies on DEAE-cellulose and benzoylated DEAE-cellulose. The misacylated tRNAPhes were assayed for participation in the peptidyltransferase reaction, using E. coli ribosomes and poly(U) as message. When phenylalanyl-tRNAPhe was employed as the A-site tRNA, "chemically aminoacylated" N-acetyl-L-phenylalanyl-tRNAPhe produced dipeptide to virtually the same extent as authentic N-acetyl-L-phenylalanyl-tRNAPhe, which was prepared by enzymatic activation of tRNAPhe followed by chemical acetylation. Significant dipeptide formation was also obtained with N-acetyl-L-tyrosyl-tRNAPhe, but much less dipeptide was obtained when the D-isomers of these two N-acetylaminoacyl-tRNAs were employed in the same assay system. Interestingly, N-acetyl-beta-phenylalanyl-tRNAPhe formed dipeptide at least to the same extent as authentic N-acetyl-L-phenylalanyl-tRNAPhe.


Effects of chronic ethanol exposure on cultured cerebellar granule cells.
The aim of this study was to investigate the lipid content and composition of rat cerebellar granule cells grown in the presence of ethanol (40, 55, or 80 mM) during in vitro differentiation. Quantitative analyses showed no effects of 40 mM ethanol, whereas a significant increase of total cholesterol was observed at 55 mM. Cells exposed to the highest ethanol dose (80 mM) were characterized by a higher sialidase activity, and by the modification of the ganglioside pattern and phospholipid fatty acid composition. The observed modifications were accompanied by changes of membrane anisotropy fluorescence assessed by the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene.


Effects of ammonium chloride on urinary pH and cigarette smoking behavior.
We determined the effects of acidification of urinary pH on cigarette smoking behavior to assess the postulated relationships between stress, urinary pH, and cigarette smoking. Urine was acidified by short-term administration of 12.5, 25, and 50 mg/kg ammonium chloride and long-term administration of 50 mg/kg ammonium chloride. Measurements of cigarette smoking behavior included the number of cigarettes smoked as well as automated measures of puff frequency and duration. Short- and long-term administration of ammonium chloride induced decreases in urinary pH but failed to induce any substantial changes in number of cigarettes smoked, puff frequency, or puff duration.


Molecular characterization of the Bacillus anthracis main S-layer component: evidence that it is the major cell-associated antigen.
Bacillus anthracis, the aetiological agent of anthrax, is a Gram-positive spore-forming bacterium. The cell wall of vegetative cells of B. anthracis is surrounded by an S-layer. An array remained when sap, a gene described as encoding an S-layer component, was deleted. The remaining S-layer component, termed EA1, is chromosomally encoded. The gene encoding EA1 (eag) was obtained on two overlapping fragments in Escherichia coli and shown to be continuous to the sap gene. The EA1 amino acid sequence, deduced from the eag nucleotide sequence, shows classical S-layer protein features (no cysteine, only 0.1% methionine, 10% lysine, and a weakly acidic pl). Similar to Sap and other Gram-positive surface proteins, EA1 has three 'S-layer-homology' motifs immediately downstream from a signal peptide. Single- and double-disrupted mutants were constructed. EA1 and Sap were co-localized at the cell surface of the wild-type bacilli. However, EA1 was more tightly bound than Sap to the bacteria. Electron microscopy studies and in vivo experiments with the constructed mutants showed that EA1 constitutes the main lattice of the B. anthracis S-layer, and is the major cell-associated antigen.


Preparation of Giant Vesicles with Mixed Single-Tailed and Double-Tailed Lipids.
Giant vesicles are model membrane systems that can be characterized with microscopy. Whereas most giant synthetic vesicles are created with a single phospholipid species, vesicles with mixed membrane compositions, including single-tailed and double-tailed lipids, serve as more accurate models of biological membranes and also have applications in the origins of life and drug delivery fields. Here we describe several approaches that can be used to create giant vesicles with mixed lipid compositions.


Health related quality of life in adults with asthma: a systematic review to identify the values of EQ-5D-5L instrument.
The EQ-5D is the most popular generic preference-based instrument used for asthma patients. This study aims to explore the psychometric properties of the EQ-5D-5L instrument in patients with asthma and identify the EQ-5D-5L scores in these patients. PubMed, Scopus, Web of Science, Google Scholar and CEA Registry were searched with English language from 2009 until April 2020. Retrieved studies were checked against the inclusion criteria. Reference lists of the included articles were also reviewed. The quality of included articles was evaluated using Mitton checklist and the data were extracted by a reviewer and were checked by a second reviewer. Meta-analysis was done to calculate the overall scores based on type of asthma control. A total of 17 articles were included. The EQ-5D-5L scores ranged from 0.45 to 0.93 and the VAS scores ranged from 35.67 to 83.80. The EQ-5D-5L is higher in well-controlled (0.88, 95% CI: 0.81-0.96, P = 0.0001) than partly controlled (0.80, 95% CI: 0.74-0.85, P = 0.001) and poorly controlled asthma (0.72, 95% CI: 0.67-0.77, P = 0.01). Validity in two studies was weak and, in other studies, it was moderate to strong. Responsiveness of the EQ-5D-5L, that was shown in a study, was less than other generic instruments, and reliability was adequate in only study that had been reported. Ceiling effects were between 8.30% to 35%. Higher score of the EQ-5D-5L was consistent with well-controlled asthma patients and those with lower severity of asthma. The assessment of psychometric properties of the EQ-5D-5L needs further observations.


Squamous cell carcinoma arising from the pleura after pneumonectomy for squamous cell carcinoma of the lung.
A 67-year-old Caucasian man had a right pneumonectomy for primary bronchogenic carcinoma in 1998. He developed a bronchopleural fistula that was managed with an Eloesser procedure. His appearance 6 years later has been published previously. We performed a case report and literature search. In 2008, the patient still had a bronchopleural fistula and reported a new symptom: constant right chest pain. He had experienced extensive asbestos exposure and mesothelioma was suspected. Endoscopy via the Eloesser aperture revealed innumerable tumor nodules. Biopsies of the pleura revealed multifocal, well-differentiated, squamous cell carcinoma with histology that was distinctly different from that of the original lung cancer. The tumor progressed rapidly during work-up and invaded the spine. He received palliative treatment but died 4 months after the onset of chest pain. We conducted a literature search and found 9 previous reports of epidermoid carcinoma arising from the pleura in patients with a chronically draining empyema; 5 patients had a prior pneumonectomy. Cancer can arise in areas of chronic inflammation such as osteomyelitis with a draining sinus, Crohn's disease, or chronic gastritis. Cases of squamous cell carcinoma arising from the pleura in patients with a chronically draining empyema cavity are extremely rare. We believe this is the sixth report in the literature of squamous cell carcinoma arising from the pleura in a patient with a chronic postpneumonectomy bronchopleural fistula. In vivo video footage of the involved pleura is available


A novel application of the fluorescent dye bis-ANS for labeling neurons in acute brain slices.
The cell-impermeant oligomer-(e.g. beta-amyloid-, or tubulin-) specific fluorescent dye, bis-ANS (4,4'-bis-1-anilinonaphtalene-8-sulfonate), was successfully used for labeling mechanically damaged but still viable neuron bodies, neurites and neurite cross sections in acute brain slices. Acute hippocampal brain slices of rats were co-stained with bis-ANS and the cell-impermeant, DNA-specific dye propidium iodide (PI) and were then analyzed using fluorescence and confocal microscopes. Both the neuron bodies and the neurites were found to exhibit increased fluorescence intensities, suggesting that using this method they can be detected more easily. In addition, bis-ANS showed good region - but not cell specific co-localization with the neuron-specific fluorescent dye Dil (1,1'-Dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate). These two dyes label different neuronal structures: Dil binds specifically to intact cell membranes while bis-ANS can enter cells with compromised cell membranes and then stain the microtubules in the cytoplasm. For a quick (10min) staining of acute brain slices with bis-ANS both HEPES and NaHCO(3) were needed in order to achieve high signal intensity. Labeling with bis-ANS fluorescent dye is an easy method for imaging the neuronal structures on the surface of acute brain slices.


Selective COSY-J-resolved-HMBC, a new method for improving sensitivity of cross peaks of methine proton signals attached to a methyl group.
Improved pulse sequences for measuring long-range C-H coupling constants ((n)J(C-H)), named selective COSY-J-resolved HMBC-1 and -2, have been developed. In the spin systems, such as -CH(C)-CH(A)(CH(3))-CH(B)-, a methine proton H(A) splits into a multiplet owing to several vicinal couplings with protons, resulting in attenuation of its cross-peak intensity. Therefore, the measurements of (n)J(C-H) with H(A) are generally difficult in the J-resolved HMBC or selective J-resolved HMBC spectrum. With the aim of accurate measurements of (n)J(C-H) in such a spin system, we have developed new pulse sequences, which transfer the magnetization of a methyl group to its adjacent methine proton. The proposed pulse sequences successfully enable to enhance the sensitivity of H(A) cross peak in comparison with the selective J-resolved HMBC pulse sequence.


Purification and primary structure of two isoforms of arenicin, a novel antimicrobial peptide from marine polychaeta Arenicola marina.
Two novel 21-residue antimicrobial peptides, arenicin-1 and arenicin-2, exhibiting activity against Gram-positive and Gram-negative bacteria and fungi, were purified from coelomocytes of marine polychaeta Arenicola marina (lugworm) by preparative gel electrophoresis and RP-HPLC. Molecular masses (2758.3 and 2772.3 Da) and complete amino acid sequences (RWCVYAYVRVRGVLVRYRRCW and RWCVYAYVRIRGVLVRYRRCW) were determined for each isoform. Each arenicin has one disulfide bond (Cys3-Cys20). The total RNA was isolated from the lugworm coelomocytes, RT-PCR and cloning were performed, and cDNA was sequenced. A 202-residue preproarenicin contains a putative signal peptide (25 amino acids) and a long prodomain. Arenicins have no structure similarity to any previously identified antimicrobial peptides.


[The occurrence of listeria encephalitis in cattle in a loose housing after the use of litter, infected with listeria bacteria, from a broiler farm. To what extent do listeria bacteria occur in the gut contents of broilers (author's transl)].
In a loose housing, four cows had to be slaughtered as an emergency measure within a few weeks because of symptoms of encephalitis. Listeria monocytogenes of type 4 b were isolated both from the brains of these cows and from the litter previously spread in the cow stables, which was obtained from a broiler farm. At the same time an investigation of the occurrence of Listeria bacteria in the faeces/gut contents of broilers was undertaken. From the contents of 2373 intestines, representing 0.1 per cent of about 2,300,000 broilers from 146 farms, Listeria monocytogenes were isolated in 4.1 per cent of the birds. The infection occurred on six broiler farms, two of them exhibited recidivation. Listeria monocytogenes of type 4 b were involved three times, type 1 was concerned on two farms, and one strain could not be typed.


Innervation of the levator scapulae, the serratus anterior, the rhomboideus and the scapular muscles in the gray kangaroo (Macropus giganteus). Comparisons are drawn to the crab-eating macaque and man.
The origin, course and distribution of the nerves to the levator scapulae, rhomboideus, serratus anterior, supraspinatus, infraspinatus, subscapularis, teres minor, deltoid, teres major and latissimus dorsi muscles were examined in 7 kangaroo body-halves. The levator scapulae and the serratus anterior formed a continuous muscle sheet arising from the transverse processes of the lower 5 cervical vertebrae and the upper 6 ribs. The rhomboideus arose from the occipital bone in addition to the cervical dorsal median raphe. Six segmental nerves from C3 to C8 innervated these 3 muscles. Each segmental nerve originated from the dorsal surface of the corresponding root of the cervicobrachial plexus. All these nerves innervated the levator-serratus muscle sheet and 4 segmental nerves from C3 to C6 innervated the rhomboideus. Of the remaining scapular muscles, the supraspinatus was well developed, and the teres minor was a small muscle. The nerves supplying the scapular muscles originated from the area between the upper trunk and the posterior cord of the brachial plexus. Four segmental nerves from C5 to C8 usually innervated these 7 muscles. Judging from the relationships between nerves and muscles, all of these muscles are thought to have originally belonged to the same 2 groups of the dorsal musculature extending between the trunk, the shoulder girdle, and the limb. Muscle type and modes of nerve supply to the muscles in the grey kangaroo are similar to those found in the crab-eating macaque.


Correction: Histidine protonation controls structural heterogeneity in the cyanobacteriochrome AnPixJg2.
Correction for 'Histidine protonation controls structural heterogeneity in the cyanobacteriochrome AnPixJg2' by Aditya G. Rao et al., Phys. Chem. Chem. Phys., 2021, DOI: 10.1039/d0cp05314g.


Les enzymes de l'espace extra-cellulaire du stratum corneum.
Synopsis Bien que le stratum corneum soit composé de cellules 'mortes', il est le siège d'une activité métabolique très importante. Mais, contrairement à la plupart d'autres tissus, cette activité a la particularité d'étre extra-cellulaire. Elle est due à des enzymes excrétées par les Corps d'Odland avec les bicouches céramidiques. Ces enzymes sont des hydrolases, elles sont identiques ou très proches de celles des lysosomes. Les principales activités observées correspondent à une (ou des) glycosidase(s), une phospholipase, une sphingomyélinase, une phosphatase, une (ou des) estérase(s), des sulfatases, des protéases. Comme les hydrolases des lysosomes, elles semblent peu spécifiques. Ce pool enzymatique pourrait jouer plusieurs rôles fondamentaux, notamment: 1. La transformation des bicouches gluco-céramidiques en bicouches ceramidiques plus lipophiles; 2. L'élimination de la membrane plasmique, dont certains produits du catabolisme, comme les acides gras et les céramides, peuvent être intégrés aux bicouches céramidiques; 3. La diminution de la cohésion entre les cornéocytes; 4. La protection contre l'intrusion de corps étrangers. Comme tout système enzymatique, les hydrolases extra-cellulaires, sont certainement soumises à des régulations. Plusieurs de ces régulations sont envisagées. A partir de considérations d'enzymologie, le pH de la base du stratum corneum peut être estiméà environ 5. En cosmétologie, les enzymes du stratum corneum sont mises à contribution pour rendre actifs des précurseurs. L'étude des conséquences des modifications de l'activité enzymatique sur l'état de la peau pourrait constituer une future voie de recherche extrêmement prometteuse.


Process Evaluation of a Motivational Interviewing Intervention in a Social Security Setting: A Qualitative Study among Work-Disabled Patients.
Purpose Return to work (RTW) may be facilitated by motivational interviewing (MI), a counseling style designed to increase motivation towards behavior change. MI's relevance in a RTW context remains however unclear. Exploring how, for whom and in what circumstances MI works is therefore necessary. Methods Eighteen people (29-60 years; sick leave > 12 weeks) with low back pain (LBP) or medically unexplained symptoms (MUS) participated in a semi-structured interview after one MI consultation. We conducted a realist-informed process evaluation to explore MI's mechanisms of impact, its outcomes and how external factors may influence these. Data were coded using thematic analysis. Results Main mechanisms were supporting autonomy, communicating with empathy and respect, facilitating feelings of competence and focusing on RTW solutions instead of hindrances. Competence support was more salient among LBP patients, whereas MUS patients benefited more from empathy and understanding. External factors were mentioned to have impacted MI's effectiveness and/or the further RTW process, being personal (e.g. acceptance of the condition), work-related (e.g. supervisor support) and societal (e.g. possibility of gradual RTW). Conclusions These results stress the importance of self-determination theory's support for autonomy, relatedness and competence, together with a solution-focused approach when stimulating patients' engagement regarding RTW. These mechanisms' instalment during RTW counseling and their long-term impact depends on both personal and system-like external factors. Belgium's social security system's premise, based on control, might actually hinder RTW instead of facilitating it. Further longitudinal research could explore MI's long-term effects as well as its complex interaction with external factors.


Solubilization of active receptors for VIP from guinea pig lung.
The zwitterionic detergent 3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propane sulfonate (CHAPS) was used to solubilize functional receptors for vasoactive intestinal peptide (VIP) from guinea pig lung. The binding of [125I]-VIP to the soluble receptors was time-dependent, reversible and saturable. Trypsin destroyed the activity of the receptors, indicating their proteinic nature. Dithiothreitol reduced the binding in a dose-dependent manner, suggesting the importance of disulfide bond(s) in receptor-binding activity. Binding of [125I]-VIP to the receptors was reversible and was competitively inhibited by unlabeled VIP, with 50% inhibition obtained at 305 nM VIP.


Thermal hysteresis in microtubule assembly/disassembly dynamics: The aging-induced degradation of tubulin dimers.
The assembly/disassembly of biological macromolecules plays an important role in their biological functionalities. Although the dynamics of tubulin polymers and their super-assembly into microtubule structures is critical for many cellular processes, details of their cyclical polymerization/depolymerization are not fully understood. Here, we use a specially designed light scattering technique to continuously examine the effects of temperature cycling on the process of microtubule assembly/disassembly. We observe a thermal hysteresis loop during tubulin assembly/disassembly, consistently with earlier reports on the coexistence of tubulin and microtubules as a phase transition. In a cyclical process, the structural hysteresis has a kinetic component that depends on the rate of temperature change but also an intrinsic thermodynamic component that depends on the protein topology, possibly related to irreversible processes. Analyzing the evolution of such thermal hysteresis loops over successive cycles, we found that the assembly/disassembly ceases after some time, which is indicative of protein aging leading to its inability to self-assemble after a finite number of temperature cycles. The emergence of assembly-incompetent tubulin could have major consequences for human pathologies related to microtubules, including aging, neurodegenerative diseases and cancer.


Contamination status and temporal trends of persistent toxic substances in sediment cores from coastal areas of central Vietnam.
Residue concentrations of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were measured in sediment core samples from two estuary areas of central Vietnam to elucidate recent status and temporal trends of pollution based on the depth profiles. Concentrations of PCBs, PBDEs, and endosulfan compounds were generally higher than those of the remaining OCPs. Peak concentrations of OCPs were found in the sediment layers corresponding to the late 1950s to the early 1980s, implying the intensive application of these insecticides in Vietnam during such periods. Although the highest PCB concentrations were measured in sediment layers dated in the 1970s, increasing PCB residues observed in the shallower layers may be related to the strong industrialization and urbanization in Vietnam. BDE-209 exhibited increasing concentrations and proportions to total PBDEs towards shallower depths, suggesting substantial use and on-going releases of deca-BDE products in recent years.


Percutaneous Coronary Intervention Planning and Optimization with Optical Coherence Tomography.
Coronary angiography confirms or excludes coronary artery disease, assesses lesions severity, and helps to decide percutaneous coronary interventions (PCI). Coronary angiography has clear limitations. Intravascular imaging guides PCI. Frequency domain optical coherence tomography (OCT) gained attention for accurate planning and guidance of complex PCI. High-speed OCT image acquisition enables prompt vessel assessment in stable and unstable patients. The high-resolution images provide precise tissue characterization and a reliable quantitative assessment of the coronary pathology. Immediately after stent implantation, OCT allows accurate evaluation of stent expansion and symmetry. Real-time angio-OCT co-registration integrates OCT into the PCI workflow for accurate decision making.


Hessian single-molecule localization microscopy using sCMOS camera.
Single-molecule localization microscopy (SMLM) has the highest spatial resolution among the existing super-resolution imaging techniques, but its temporal resolution needs further improvement. An sCMOS camera can effectively increase the imaging rate due to its large field of view and fast imaging speed. Using an sCMOS camera for SMLM imaging can significantly improve the imaging time resolution, but the unique single-pixel-dependent readout noise of sCMOS cameras severely limits their application in SMLM imaging. This paper develops a Hessian-based SMLM (Hessian-SMLM) method that can correct the variance, gain, and offset of a single pixel of a camera and effectively eliminate the pixel-dependent readout noise of sCMOS cameras, especially when the signal-to-noise ratio is low. Using Hessian-SMLM to image mEos3.2-labeled actin was able to significantly reduce the artifacts due to camera noise.


Target concentration strategy for cyclosporin monitoring.
The target concentration concept has been proposed as a potential alternative to the established, and probably much abused, therapeutic range method of interpreting concentrations of therapeutic drugs in plasma, serum or blood when individualising drug dosages. This paper raises for debate the possibility of extending this alternative concept to immunosuppressant monitoring with cyclosporin, where there has been considerable difficulty in establishing therapeutic ranges which are widely accepted and applied. In its broader application, the target concentration strategy does present advantage to the clinician in precision, ability to calculate the dose directly from the target concentration and clearance, as well as a clearer concept of an optimal concentration (differentiating desired and adverse effects).


CDP-ethanolamine:1,2-diacylglycerol ethanolaminephosphotransferase.
Ethanolaminephosphotransferase catalyzes the final step of the CDP-ethanolamine pathway for the de novo synthesis of phosphatidylethanolamine (PtdEtn) via transfer of a phosphoethanolamine moiety from CDP-ethanolamine to diacylglycerol for the formation of PtdEtn and CMP. Ethanolaminephosphotransferase is an integral membrane-bound enzyme whose intracellular location defines the site of PtdEtn synthesis by the CDP-ethanolamine pathway. Subcellular fractionation experiments have yet to resolve the precise subcellular location of ethanolaminephosphotransferase, although it is routinely associated with the microsomal fraction. Ethanolaminephosphotransferase has yet to be purified from any source and its cDNA has not been isolated from any mammalian source, thus preventing the generation of antibodies necessary to directly examine its intracellular location through immunofluorescence or electron microscopy approaches. An ethanolaminephosphotransferase gene has recently been isolated from the yeast Saccharomyces cerevisiae and structure/function analyses of the encoded enzyme identified several important characteristics including the catalytic site. The predicted amino acid sequence of the S. cerevisiae ethanolaminephosphotransferase gene should allow for the generation of antibodies required to directly define the site of PtdEtn synthesis in this organism, and it has provided the necessary information to pursue the isolation of a mammalian cDNA.


Electron microscope study of the binding of Con A-gold to superficial and inner ectoderm layers ofXenopus laevis and its relation to the neural-inducing activity of this lectin.
Isolated competent amphibian ectoderm differentiates into neural (archencephalic) structures when treated with the plant lectin concanavalin A (Con A). While the inner ectoderm layer ofXenopus laevis forms brain structures after incubation with Con A, the outer ectoderm layer differentiates into ciliated epidermis only. This difference can be correlated with the pattern of Con A bound to the plasma membrane. With gold-labelled Con A it could be shown by transmission electron microscopy (TEM) that the outer ectoderm binds substantially less lectin than the inner layer. Furthermore we observed characteristic differences at the apical and basal surfaces of the cells of the same layer, i.e. on the apical cell surface of the superficial layer almost no Con A-gold could be found. In contrast, we observed a lot of gold particles on the basal cell side of the superficial layer. However, the number on both surfaces (apical and basal side of the cell) of the inner ectoderm layer was essentially higher, which could explain its biological reaction to the Con A stimulus and the differentiation into neural structures. The data presented in this paper indicate that early and late gastrula ectoderm bind similar amounts of Con A and support the view that the decrease in competence is not correlated with a loss of receptors for inducing factors. Furthermore, we describe the binding and the internalization of Con A via receptor-mediated endocytosis and the further fate of the Con A-gold-receptor complex inside the target cell.


[Autism spectrum disorders in adulthood: clinical and neuropsychological findings of Aspergers syndrome diagnosed late in life].
High-functioning autism (HFA) and Aspergers syndrome (AS) are autism spectrum disorders (ASD) characterised by disturbances in social interaction, both verbal and non-verbal communication and repetitive and/or restrictive behaviour since early childhood. Symptoms appear generally during early childhood and adolescence. The increasing need to clarify diagnostic queries in advanced age led to the constitution of specialised outpatient clinics for adults involving a growing amount of HFA/AS subjects diagnosed late in life. However, thus far neuropsychological data about this group are scarce. We present a subgroup of 39 patients with HFA/AS (mean age at diagnosis 31.1 ± 8.9 years) who were consecutively diagnosed at the autism outpatient clinic at the Department of Psychiatry at the University Hospital Cologne. Autistic symptoms (autism spectrum quotient; AQ), depressive symptoms (Beck depression inventory; BDI), general intelligence (HAWIE-R), social cognition ("theory of mind", ToM) and executive functioning (COWAT) were systematically studied in comparison to a control group matched for age, education, gender and intelligence (n = 39). HFA/AS subjects presented higher AQ scores (40.4 ± 5.2) as opposed to the healthy controls (13.5 ± 4.8). Neuropsychologically, patients showed deficits in social cognition, executive functions and in subtests of HAWIE-R related to verbal comprehension and perceptual organisation as opposed to the healthy control group. The diagnosis of autistic disorders in adulthood basically relies on the clinical assessment of autistic core symptoms which were corroborated by high AQ values. The self-rating instrument AQ was found to be highly discriminative between the HFA/AS group and the healthy control group. The neuropsychological profile of adult HFA/AS patients diagnosed late in life is compatible with that of previously investigated HFA/AS populations. These findings show that such basic autism-associated deficits persist until adulthood, although patients are able to learn social rules.


Chromosomal localization of the HYP2-gene in Saccharomyces cerevisiae and use of pulsed-field gel electrophoresis for detection of irregular recombination events in gene disruption experiments.
In the hypusine-containing protein (HP), a specific lysine residue is modified by spermidine to form the unusual amino acid hypusine (4-amino-2-hydroxybutyllysine). The HP has been designated as an eucaryotic translation initiation factor--eIF-5A--because of its stimulating effect in the methionyl-puromycin in vitro assay. Nevertheless, the precise function of this protein remains to be elucidated. In the yeast Saccharomyces cerevisiae two genes, HYP1 and HYP2, coding for two different forms of the HP, are present. The HYP1-gene is identical to the ANB1-gene and has already been localized on chromosome X. However, the chromosomal localization of the HYP2-gene has not been elucidated. By using pulsed-field gel electrophoresis (PFGE) and subsequent Southern blotting, we determined the localization of the HYP2-gene to chromosome V. Furthermore, PFGE was used for the detection of irregular recombination events, such as misintegration or integration into a duplicated gene, and in gene disruption experiments using haploid and diploid yeast cells. The obtained data support the critical role of the HP for cell viability.


4-(Diethyl-amino)-salicyl-aldehyde azine.
The title compound, C(22)H(30)N(4)O(2), has a crystallographic inversion center located at the mid-point of the N-N single bond. Apart from the four ethyl C atoms, the non-H atoms are nearly coplanar with a mean deviation of 0.0596 (2) Å. An intra-molecular O-H⋯N hydrogen bond occurs. In the crystal, weak inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into layers parallel to (100).


Peri-operative hemostatic management of tooth extraction in patients with hemophilia A, with and without inhibitors, receiving emicizumab prophylaxis.
Emicizumab treatment may allow patients with hemophilia A without (PwHA) and with inhibitors (PwHA-I) to undergo some minor surgeries, such as tooth extraction, without peri-operative factor infusions. However, criteria for determining the necessity of factor infusions before minor surgeries are unknown. We report the peri-operative hemostatic management and outcomes of emicizumab-treated PwHA and PwHA-I cases who underwent tooth extractions using our institutional protocol. We retrospectively evaluated PwHA and PwHA-I who underwent tooth extraction with emicizumab prophylaxis at our institution. Local bleeding risk was assessed based on the method, number, and site of tooth extraction. Hemostasis was monitored peri-operatively by rotational thromboelastometry (ROTEM). Hemostatic agents and a mouth splint were used. Twenty-nine extractions (17 interventions) were performed in eight PwHA and two PwHA-I. Based on ROTEM, pre-operative factor infusions were used in ten PwHA and four PwHA-I interventions. Among nine low local bleeding risk interventions, three (33.3%) each received no infusions, one dose of factor infusion pre-operatively, and pre- and post-operative factor infusions. All eight high local bleeding risk interventions involved planned factor infusions. Absorbable hemostats were used in all extractions. A mouth splint was used in 21/25 (84.0%) PwHA and in 4/4 (100%) PwHA-I extractions. No post-extraction bleeding or thrombotic events occurred. Use of a systemic hemostatic treatment plan according to the local bleeding risk, peri-operative coagulation status assessment using ROTEM, filling the extraction socket with hemostats, and use of a mouth splint can achieve effective and safe hemostatic management in emicizumab-treated PwHA and PwHA-I.


Goal quest for an intelligent surfer moving in a chaotic flow.
We consider a model of an intelligent surfer moving on the Ulam network generated by a chaotic dynamics in the Chirikov standard map. This directed network is obtained by the Ulam method with a division of the phase space in cells of fixed size forming the nodes of a Markov chain. The goal quest for this surfer is to determine the network path from an initial node A to a final node B with minimal resistance given by the sum of inverse transition probabilities. We develop an algorithm for the intelligent surfer that allows us to perform the quest in a small number of transitions which grows only logarithmically with the network size. The optimal path search is done on a fractal intersection set formed by nodes with small Erdös numbers of the forward and inverted networks. The intelligent surfer exponentially outperforms a naive surfer who tries to minimize its phase space distance to target B. We argue that such an algorithm provides unique hints for motion control in chaotic flows.


How do we leave lockdown?
With more than a third of the world living under covid-19 restrictions, it is time to decide what happens next, reports Graham Lawton.


The impact of postoperative cognitive training on health-related quality of life and cognitive failures in daily living after heart valve surgery: A randomized clinical trial.
Heart surgery is a risk factor for objectively and subjectively assessable postoperative cognitive decline (POCD), which is relevant for everyday life. The aim of this study was to investigate whether early postoperative cognitive training has an impact on health-related quality of life and cognitive failures in daily living after cardiac surgery. The study was a two-arm, randomized, controlled, outcome-blinded trial involving older patients undergoing elective heart valve surgery with extracorporeal circulation (ECC). Recruitment took place at the Departments of Cardiac Surgery of the Kerckhoff Clinic in Bad Nauheim (Germany) and the University Hospital in Giessen (Germany). The patients were randomized (1:1 ratio) to either a paper-and-pencil-based cognitive training group or a control group. We applied the Short Form Health Survey (SF-36) and the Cognitive Failures Questionnaire (CFQ) prior to surgery and 3 months after the cognitive training. Data were analyzed in a per-protocol fashion. Three months after discharge from rehabilitation, the training group (n = 31) showed improvement in health-related quality of life compared to the control group (n = 29), especially in role limitations due to emotional problems (U = -2.649, p = .008, η2 = 0.121), energy and fatigue (F[2.55] = 5.72, p = .020, η2 = 0.062), social functioning (U = -2.137, p = .033, η2 = 0.076), the average of all SF-36 factors (U = -2.374, p = .018, η2 = 0.094), health change from the past year to the present time (U = -2.378, p = .017, η2 = 0.094), and the mental component summary (U = -2.470, p = .013, η2 = 0.102). As our cognitive training has shown beneficial effects, this intervention could be a promising method to enhance health-related quality of life after cardiac surgery.


The redox cycling of STAT2 maintains innate immune homeostasis.
Interferons (IFNs) are essential in antiviral defense, antitumor effects, and immunoregulatory activities. Although methionine oxidation is associated with various physiological and pathophysiological processes in plants, animals, and humans, its role in immunity remains unclear. We find that the redox cycling of signal transducer and activator of transcription 2 (STAT2) is an intrinsic cellular biological process, and that impairment of the redox status contributes to STAT2 methionine oxidation, inhibiting its activation. IFN protects STAT2 from methionine oxidation through the recruitment of methionine sulfoxide reductase MSRB2, whose enzymatic activity is enhanced by N-acetyltransferase 9 (NAT9), a chaperone of STAT2 defined in this study, upon IFN treatment. Consequently, loss of Nat9 renders mice more susceptible to viral infection. Our study highlights the key function of methionine oxidation in immunity, which provides evidence for the decline of immune function by aging and may provide insights into the clinical applications of IFN in immune-related diseases.


[Biological effects of allogenic leukocytes and leukocyte-depleted blood cell products].
The use of leukodepleted cellular blood components may reduce some adverse effect of transfusion in certain indications. This review presents the adverse effects of contaminating donor leukocytes in blood components: alloimmunisation, febrile nonhemolytic transfusion reactions, refractoriness to platelet transfusions, graft versus host disease, transmission of leukotropic infections and immunomodulation. The value of leukodepletion in preventing some of these complications, methods of leukodepletion and the current indications of use of leukodepleted components in clinical practice are discussed.


Measuring the incentive value of escalating doses of heroin in heroin-dependent Fischer rats during acute spontaneous withdrawal.
Although continued heroin use and relapse are thought to be motivated, in part, by the positive incentive-motivational value attributed to heroin, little is understood about heroin's incentive value during the relapse-prone state of withdrawal. This study uses place preference to measure the incentive value attributed to escalating-dose heroin in the context of heroin dependence. Male Fischer rats were exposed chronically to escalating doses of heroin in the homecage and during place preference conditioning sessions. Conditioned preference for the context paired with escalating-dose heroin was tested after homecage exposure was discontinued and rats entered acute spontaneous withdrawal. Individuals' behavioral and locomotor responses to heroin and somatic withdrawal signs were recorded. Conditioned preference for the heroin-paired context was strong in rats that received chronic homecage exposure to escalating-dose heroin and were tested in acute withdrawal. Behavioral responses to heroin (e.g., stereotypy) varied widely across individuals, with rats that expressed stronger heroin preference also expressing stronger behavioral activation in response to heroin. Individual differences in preference were also related to locomotor responses to heroin but not to overt somatic withdrawal signs. Escalating doses of heroin evoked place preference in rats, suggesting that positive incentive-motivational value is attributed to this clinically relevant pattern of drug exposure. This study offers an improved preclinical model for studying dependence and withdrawal and provides insight into individual vulnerabilities to addiction-like behavior.


Use of acid-fast bacilli staining to determine the need for airborne infection isolation precautions: a comparison of respiratory specimens.
Institution of appropriate airborne infection isolation (AII) precautions for patients with suspected Mycobacterium tuberculosis is critical to prevent disease transmission. We compared the yield of acid-fast bacilli smears from different types of respiratory specimens and found that smear sensitivity was highest for specimens obtained by endotracheal aspirates (92%), followed by sputum (79%), and then by bronchoalveolar lavage (37%). As a result of this study, our institutional policy regarding discontinuation of AII precautions was amended.


Determination of incidence rates for chronic mastitis using heifer prevalence data.
Two methods for calculating the incidence rate for staphylococcal mastitis were investigated, using prevalence data among heifers. A method utilizing bacteriologic culture results from prevalence surveys, clinical cases, and fresh heifers was more sensitive in determining incidence rates than was a method utilizing results from serial prevalence surveys only.


Autonomic nervous regulation of ovarian function by noxious somatic afferent stimulation.
It is well known that ovarian function is regulated by hypothalamic-pituitary-ovarian hormones. However, although several histological studies have described the autonomic innervation of the ovary, the involvement of these autonomic nerves in ovarian function is unclear. Recently, it has been shown that both the superior ovarian nerve (SON) and the ovarian nerve plexus (ONP) induce vasoconstrictor activity by activation of alpha 1-adrenoceptors, whereas the SON, but not the ONP, inhibits ovarian estradiol secretion by activation of alpha 2-adrenoceptors. Furthermore, reflex activation of these ovarian nerves by noxious cutaneous stimulation of the rat hindpaw results in ovarian vasoconstriction and inhibition of estradiol secretion. Thus, in addition to long-term regulation of ovarian function by hormones, ovarian autonomic innervation may be involved in rapid regulation of ovarian function by responding to either internal or external environmental changes.


The Effect of Hypotensive Anesthesia on Hemoglobin Levels during Total Knee Arthroplasty.
Hypotensive epidural anesthesia (HEA) is used in total joint arthroplasty as a safe and effective blood-saving modality. In order to maintain the blood pressure and heart rate patients, receive 1000 to 1500 mL of lactated Ringer's solution during surgery. While HEA reduces the intraoperative blood loss, the effect of intravenous fluid loading on hemoglobin levels is not fully understood. The current study investigates the effect of HEA on perioperative hemoglobin levels. The study included 35 patients operated on by a single surgeon undergoing primary total knee arthroplasty under HEA. Intraoperatively, at least 300 mL of intravenous fluid were given every 15 min over the first 60 min after HEA. Blood samples were drawn before entering the operating room, after HEA, as well as after inflation of the tourniquet, every 15 min thereafter, as well as in the recovery room and on postoperative days one and two. In addition, fluid in- and outtake was recorded. Patients received a mean 1275 mL during the 60 min of tourniquet time. The mean arterial pressure (MAP) 5 min after HEA dropped to 60 mmHg and reached a constant level of around 58 mmHg 15 min after HEA. The average hemoglobin level dropped from 13.9 g/dL prior to HEA, to 12.5 g/dL immediately after HEA (p < 0.001). Intraoperatively the hemoglobin level dropped further and reached 11.8 g/dL at 60 min in the absence of blood loss. Hypotensive epidural anesthesia and the resulting fluid substitution resulted in an average hemoglobin drop of 2.1 g/dL within the first 60 min. This needs to be taken into account when evaluating the need for blood transfusions after primary joint replacement surgery under HEA.