Binding of tissue-plasminogen activator to fibrin: effect of ultrasound.
Ultrasound reversibly alters the structure of polymerized fibrin, an effect that could influence tissue-plasminogen activator (t-PA) binding. We have, therefore, characterized the effects of ultrasound on binding of t-PA to fibrin using a novel system in which radiolabeled, active-site blocked, single chain tissue-plasminogen activator flowed through a fibrin gel at constant rate, and specific binding was determined by monitoring incorporation of radiolabel. Results using polymerized fibrin were compared with those using a surface of fibrin immobilized on Sepharose beads in a similar system. Interaction of t-PA with surface-immobilized fibrin involved two classes of binding sites (Kd = 31 nmol/L and 244 nmol/L) and a maximum binding ratio of 3.8 mol t-PA/mol fibrin. Ultrasound increased Kd for the high affinity site to 46 nmol/L (P < .0001), but it had no significant effects on the Kd 244 nmol/L site nor on Bmax. Tissue-plasminogen activator binding to noncrosslinked fibrin involved two sites with Kds of 267 nmol/L and 952 nmol/L, while a single Kd 405 nmol/L site was identified for crosslinked fibrin. Ultrasound had no significant effect on the binding affinity for noncrosslinked fibrin, but Bmax was increased in the presence of ultrasound, from 31 mumol/L to 43 mumol/L (P < .0001). Ultrasound decreased the Kd for crosslinked fibrin to 343 nmol/L (P = .026) and also increased Bmax from 22 mumol/L to 25 mumol/L (P = .015). Ultrasound also affected the kinetics of t-PA binding to fibrin, significantly accelerating the rate of dissociation by 77% +/- 5% for noncrosslinked fibrin and by 69% +/- 3% for crosslinked fibrin (P < .001 for each). These results indicate that ultrasound exposure accelerates t-PA binding, alters binding affinity, and increases maximum binding to polymerized fibrin, effects that may result from ultrasound-induced changes in fibrin structure.


Annona glabra L. Seeds: An Agricultural Waste Biosorbent for the Eco-Friendly Removal of Methylene Blue.
The seeds of Annona glabra L., an invasive plant in Vietnam, were first employed as a new biosorbent for the adsorption of methylene blue (MB) from aqueous media. The characterizations of the material using FT-IR, SEM, nitrogen adsorption-desorption analysis, and point of zero charge reveals that it possesses a rough and irregular surface, various polar functional groups, and pHpzc of 5.5. Certain adsorption conditions including adsorbent dose, solution pH, contact time, and initial concentration of MB were found to affect adsorption efficiency. The kinetic data are well fitted with pseudo-second-order model with the adsorption rate of 0.002 g mg-1 min-1 and initial rate of 4.46 mg g-1 min-1. For the adsorption isotherm, three nonlinear models were used to analyze the experiment data, including Langmuir, Freundlich, and Temkin. The results indicate that the Langmuir model best describes the adsorption of Annona glabra L. seeds powder (AGSP) with a maximum adsorption capacity of 98.0 mg g-1. The investigation underpins the adsorption mechanism, whereby the electrostatic attraction between positively charged MB and negatively charged surface of AGSP is expected to be the predominant mechanism, together with hydrogen bonding and pi-pi interaction. These results make AGSP an interesting biosorbent concerning its environmental friendliness, cost-effectiveness, and relatively high dye adsorption capacity.


Consumption of Brazil nuts with high selenium levels increased inflammation biomarkers in obese women: A randomized controlled trial.
Increased inflammatory response is an important factor in the pathophysiology of obesity. The mineral selenium (Se), of which one of the main food sources is the Brazil nut, has important antioxidant and anti-inflammatory functions through the action of selenoproteins. Thus, the evaluation of the influence of this micronutrient in this context is of great relevance. The aim of this study was to evaluate the effects of Brazil nut intake with high Se concentrations on inflammatory biomarkers and its relation to Se status in obese women. A randomized controlled clinical trial was carried out with 55 women recruited at Clinical Hospital in São Paulo, Brazil. Patients were randomly assigned to either the Brazil nut group (BN) or the control group (CO) and followed up for 2 mo. The BN group consumed 1 unit/d of Brazil nuts (∼ 1261 μg/Se); the CO group did not receive any intervention. At baseline and after 2 mo, analysis of biochemical parameters related to Se status, oxidative stress, and inflammatory biomarkers were performed. At baseline, both groups did not present Se deficiency. In the BN group, a significant increase (P < 0.05) in all Se biomarkers and in gene expression of several proinflammatory parameters (interleukin-6, tumor necrosis factor-α, and Toll-like receptors 2 and 4) were observed after the intervention period. No changes were observed for the CO group. Although there were no changes in plasma inflammatory biomarkers levels, a significant increase in gene expression may be an indication of a proinflammatory stimulus in obesity, induced by the consumption of Brazil nuts with high Se levels.


Lateral shearing interferometry of high-harmonic wavefronts.
We present a technique for frequency-resolved wavefront characterization of high harmonics based on lateral shearing interferometry. Tilted replicas of the driving laser pulse are produced by a Mach-Zehnder interferometer, producing separate focii in the target. The interference of the resulting harmonics on a flat-field extreme ultraviolet spectrometer yields the spatial phase derivative. A comprehensive set of spatial profiles, resolved by harmonic order, validate the technique and reveal the interplay of single-atom and macroscopic effects.


[Congenital cardiopathies in the newborn].
Ten years experience in newborn congenital cardiac malformations with severe hemodynamic changes is reported. The anatomic diagnosis was made at necropsy (85%) or by cardiac catheterization and angiocardiography (15%). One hundred and twenty-six cases were found in which aortic valve atresia or stenosis, tricuspid atresia, cardiac anomalies associated to visceral heterotaxy, tetralogy of Fallot, aortic coartation, endocardial cushion defect, ventricular septal defect, total anomalous pulmonary venous return and pulmonary atresia with intact ventricular septum were the most common malformations. They presented with either cardiac insufficiency or hypoxia and acidosis. The principal anatomic features of these cases were discussed and the associated malformations in other systems was noted.


Application of two morphologies of Mn2O3 for efficient catalytic ortho-methylation of 4-chlorophenol.
Vapor phase ortho-methylation of 4-chlorophenol with methanol was studied over Mn2O3 catalyst with two kinds of morphologies. Here, Mn2O3 was prepared by a precipitation and hydrothermal method, and showed the morphology of nanoparticles and nanowires, respectively. XRD characterization and BET results showed that, with the increase of calcination temperature, Mn2O3 had a higher crystallinity and a smaller specific surface area. N2 adsorption/desorption and TPD measurements indicated that Mn2O3 nanowires possessed larger external surface areas and more abundant acid and base sites. Simultaneously, in the fixed bed reactor, methanol was used as the methylation reagent for the ortho-methylation reaction of 4-chlorophenol. XRD, XPS, TG-MS and other characterizations made it clear that methanol reduced 4-chlorophenol and its methide, which were the main side-reactions. And Mn3+ was reduced to Mn2+ under the reaction conditions. Changing the carrier gas N2 to a H2/Ar mixture further verified that the hydrogen generated by the decomposition of methanol was not the reason for dechlorination of 4-chlorophenol compounds. Here we summarized the progress of 4-chlorophenol methylation based on the methylation of phenol. Also, we proposed a mechanism of the 4-chlorophenol dechlorination effect which was similar to the Meerwein-Ponndorf-Verley-type (MPV) reaction. The crystal phase and carbon deposition were investigated in different reaction periods by XRD and TG-DTA. The reaction conditions for the two kinds of morphologies of the Mn2O3 catalyst such as calcination temperature, reaction temperature, phenol-methanol ratio and reaction space velocity were optimized.


Hydrogen Sulfide Protects Retinal Ganglion Cells Against Glaucomatous Injury In Vitro and In Vivo.
Hydrogen sulfide (H2S) is recognized as a novel third signaling molecule and gaseous neurotransmitter. Recently, cell protective properties within the central nervous and cardiovascular system have been proposed. Our purpose was to analyze the expression and neuroprotective effects of H2S in experimental models of glaucoma. Elevated IOP was induced in Sprague-Dawley rats by means of episcleral vein cauterization. After 7 weeks, animals were killed and the retina was analyzed with label-free mass spectrometry. In vitro, retinal explants were exposed to elevated hydrostatic pressure or oxidative stress (H2O2), with and without addition of a slow-releasing H2S donor Morpholin-4-ium-methoxyphenyl-morpholino-phosphinodithioate (GYY4137). In vivo, GYY4137 was injected intravitreally in animals with acute ischemic injury or optic nerve crush. Brn3a+ retinal ganglion cells (RGCs) were counted in retinal flat mounts and compared. Optical coherence tomography (OCT) was performed to examine the vessels. Comparisons were made by t-test and ANOVA (P < 0.05). IOP elevation caused significant RGC loss (P < 0.001); 3-mercaptosulfurtransferase, an H2S producing enzyme, showed a 3-fold upregulation within the retina after IOP elevation. GYY4137 protected RGCs against elevated pressure and oxidative stress in vitro depending on the concentration used (P < 0.005). In vivo, intravitreal administration of GYY4137 preserved RGCs from acute ischemic injury and optic nerve crush (P < 0.0001). Retinal vessel diameters enlarged after intravitreal GYY4137 injection (P < 0.0001). H2S is specifically regulated in experimental glaucoma. By scavenging reactive oxygen species and dilating retinal vessels, H2S may protect RGCs from pressure and oxidative stress-induced RGC loss in vitro and in vivo. Therefore, H2S might be a novel neuroprotectant in glaucoma.


Self-Efficacy, Satisfaction, and Academic Achievement: The Mediator Role of Students' Expectancy-Value Beliefs.
Although there is considerable evidence to support the direct effects of self-efficacy beliefs on academic achievement, very few studies have explored the motivational mechanism that mediates the self-efficacy-achievement relationship, and they are necessary to understand how and why self-efficacy affects students' academic achievement. Based on a socio-cognitive perspective of motivation, this study examines the relationships among academic self-efficacy, students' expectancy-value beliefs, teaching process satisfaction, and academic achievement. Its main aim is to identify some motivational-underlying processes through which students' academic self-efficacy affects student achievement and satisfaction. Student achievement and satisfaction are two of the most important learning outcomes, and are considered key indicators of education quality. The sample comprises 797 Spanish secondary education students from 36 educational settings and three schools. The scales that referred to self-efficacy and expectancy-value beliefs were administered at the beginning of the course, while student satisfaction and achievement were measured at the end of the course. The data analysis was conducted by structural equation modeling (SEM). The results revealed that students' expectancy-value beliefs (Subject value, Process expectancy, Achievement expectancy, Cost expectancy) played a mediator role between academic self-efficacy and the achievement/satisfaction relationship. These results provided empirical evidence to better understand the mechanism that mediates self-efficacy-achievement and efficacy-course satisfaction relationships. The implications of these findings for teaching and learning in secondary education are discussed.


Zucker and Wistar diabetic fatty rats show different response to adrenalectomy.
The short-term effects of adrenalectomy on certain aspects of glucose homeostasis and adiposity were examined in Zucker and Wistar diabetic fatty (WDF) rats. Ten-week-old male obese and lean WDF and Zucker rats were adrenalectomized or underwent sham operation. Obese rats of each strain were pair fed the intake of obese adrenalectomized rats. Intragastric glucose tolerance tests showed that sham-operated obese rats of both strains were severely hyperinsulinemic compared with leans; adrenalectomy and pair feeding reduced palsma insulin to lean levels in Zucker but not WDF rats. At the time they were killed, sham-operated obese WDF rats were significantly hyperglycemic and hyperinsulinemic compared with other groups, but adrenalectomy reduced plasma glucose and insulin to lean levels in both strains. Adrenalectomy reduced inguinal and retroperitoneal fat pad weights more in Zucker than WDF obese rats. Although adrenalectomy decreased epididymal and inguinal fat cell size in both obese rat strains, the effect was greater in Zucker compared with WDF rats. These data suggest that the basis for the differential response to adrenalectomy in obese WDF and Zucker rats may reside in their different genetic backgrounds.


Kaolin alleviates the toxicity of graphene oxide for mammalian cells.
The development of novel nanoscale vehicles for drug delivery promotes the growth of interest in investigations of interaction between nanomaterials. In this paper, we report the in vitro studies of eukaryotic cell physiological response to incubation with graphene oxide and planar kaolin nanoclay. Graphene family materials, including graphene oxide (GO), hold promise for numerous applications due to their unique electronic properties. However, graphene oxide reveals toxicity to some cell lines through an unidentified mechanism. Thus, methods and agents reducing the toxicity of graphene oxide can widen its practical application. We used a colorimetric test, flow cytometry and cell index assay methods to evaluate the effects of separate and combined application of graphene oxide and kaolin on mammalian cells. We have shown that the joint application of graphene oxide and kaolin reduced the negative effects of graphene by almost 20%, most likely because of coagulation of the nanoparticles with each other, which was detected by atomic force microscopy.


Ten things every neurologist needs to know about neuropsychological assessments and interventions in people with epilepsy.
This paper describes 10 core features of a neuropsychological assessment with the aim of helping neurologists understand the unique contribution the evaluation can make within the wider context of diagnostic methods in epilepsy. The possibilities, limitations and cautions associated with the investigation are discussed under the following headings. (1) A neuropsychological assessment is a collaborative investigation. (2) Assessment prior to treatment allows for the accurate assessment of treatment effects. (3) The nature of an underlying lesion and its neurodevelopmental context play an important role in shaping the associated neuropsychological deficit. (4) Cognitive and behavioural impairments result from the essential comorbidities of epilepsy which can be considered as much a disorder of cognition and behaviour as of seizures. (5) Patients' subjective complaints can help us understand objective cognitive impairments and their underlying neuroanatomy, resulting in improved patient care. At other times, patient complaints reflect other factors and require careful interpretation. (6) The results from a neuropsychological assessment can be used to maximize the educational and occupational potentials of people with epilepsy. (7) Not all patients are able to engage with a neuropsychological assessment. (8) There are limitations in assessments conducted in a second language with tests that have been standardized on different populations from that of the patient. (9) Adequate intervals between assessments maximize sensitivity to meaningful change. (10) Patients should be fully informed about the purpose of the assessment and have realistic expectations of the outcome prior to referral.


A Comparison of Acoustic Radiation Force-Derived Indices of Cardiac Function in the Langendorff Perfused Rabbit Heart.
In the past decade, there has been an increased interest in characterizing cardiac tissue mechanics utilizing newly developed ultrasound-based elastography techniques. These methods excite the tissue mechanically and track the response. Two frequently used methods, acoustic radiation force impulse (ARFI) and shear-wave elasticity imaging (SWEI), have been considered qualitative and quantitative techniques providing relative and absolute measures of tissue stiffness, respectively. Depending on imaging conditions, it is desirable to identify indices of cardiac function that could be measured by ARFI and SWEI and to characterize the relationship between the measures. In this study, we have compared two indices (i.e., relaxation time constant used for diastolic dysfunction assessment and systolic/diastolic stiffness ratio) measured nearly simultaneously by M-mode ARFI and SWEI techniques. We additionally correlated ARFI-measured inverse displacements with SWEI-measured values of the shear modulus of stiffness. For the eight animals studied, the average relaxation time constant ( τ) measured by ARFI and SWEI were ([Formula: see text]) and ([Formula: see text]), respectively ([Formula: see text]). Average systolic/diastolic stiffness ratios for ARFI and SWEI measurements were 6.01±1.37 and 7.12±3.24, respectively ([Formula: see text]). Shear modulus of stiffness (SWEI) was linearly related to inverse displacement values (ARFI) with a 95% CI for the slope of 0.010-0.011 [Formula: see text] ( R(2)=0.73). In conclusion, the relaxation time constant and the systolic/diastolic stiffness ratio were calculated with good agreement between the ARFI- and SWEI-derived measurements. ARFI relative and SWEI absolute stiffness measurements were linearly related with varying slopes based on imaging conditions and subject tissue properties.


Induction of chromosomal aberrations (unstable and stable) by inhibitors of topoisomerase II, m-AMSA and VP16, using conventional Giemsa staining and chromosome painting techniques.
Frequencies of symmetrical and asymmetrical exchange aberrations induced by two inhibitors of topoisomerase II, namely, 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA) and etoposide (VP16), were estimated in human peripheral blood lymphocytes. The aberrations were scored using conventional Giemsa staining and fluorescence in situ hybridization (FISH) techniques, using chromosome-specific DNA libraries. Stable aberrations (translocations) were detected using two cocktails of DNA libraries specific for three chromosomes, namely 1, 3 and X and 2, 4 and 8, representing approximately 40% of the whole human genome. The frequencies of dicentrics and translocations increased in a dose-dependent manner, however, m-AMSA was found to be a more potent inducer of chromosomal aberrations in comparison with VP16 (at concentrations at which comparable frequencies of aberrations were induced) by 20- to 30-fold. When corrected for DNA content of chromosomes in each cocktail, a higher frequency of translocations with the cocktail consisting of chromosomes 2, 4 and 8 in comparison with 1, 3 and X was evident. The genomic translocation frequency calculated from chromosome painting analysis for m-AMSA exceeded that estimated for dicentrics by approximately 2-fold. However, for VP16 almost equal frequencies of both types of chromosome exchange were found.


The Role of microRNAs in Gene Expression and Signaling Response of Tumor Cells to an Acidic Environment.
Many tumors are characterized by marked extracellular acidosis due to increased glycolytic metabolism, which affects gene expression and thereby tumor biological behavior. At the same time, acidosis leads to altered expression of several microRNAs (Mir7, Mir183, Mir203, Mir215). The aim of this study was to analyze whether the acidosis-induced changes in cytokines and tumor-related genes are mediated via pH-sensitive microRNAs. Therefore, the expression of Il6, Nos2, Ccl2, Spp1, Tnf, Acat2, Aox1, Crem, Gls2, Per3, Pink1, Txnip, and Ypel3 was examined in acidosis upon simultaneous transfection with microRNA mimics or antagomirs in two tumor lines in vitro and in vivo. In addition, it was investigated whether microRNA expression in acidosis is affected via known pH-sensitive signaling pathways (MAPK, PKC, PI3K), via ROS, or via altered intracellular Ca2+ concentration. pH-dependent microRNAs were shown to play only a minor role in modulating gene expression. Individual genes (e.g., Ccl2, Txnip, Ypel3) appear to be affected by Mir183, Mir203, or Mir215 in acidosis, but these effects are cell line-specific. When examining whether acid-dependent signaling affects microRNA expression, it was found that Mir203 was modulated by MAPK and ROS, Mir7 was affected by PKC, and Mir215 was dependent on the intracellular Ca2+ concentration. Mir183 could be increased by ROS scavenging. These correlations could possibly result in new therapeutic approaches for acidotic tumors.


Clinically translatable cell tracking and quantification by MRI in cartilage repair using superparamagnetic iron oxides.
Articular cartilage has very limited intrinsic regenerative capacity, making cell-based therapy a tempting approach for cartilage repair. Cell tracking can be a major step towards unraveling and improving the repair process of these therapies. We studied superparamagnetic iron oxides (SPIO) for labeling human bone marrow-derived mesenchymal stem cells (hBMSCs) regarding effectivity, cell viability, long term metabolic cell activity, chondrogenic differentiation and hBMSC secretion profile. We additionally examined the capacity of synovial cells to endocytose SPIO from dead, labeled cells, together with the use of magnetic resonance imaging (MRI) for intra-articular visualization and quantification of SPIO labeled cells. Efficacy and various safety aspects of SPIO cell labeling were determined using appropriate assays. Synovial SPIO re-uptake was investigated in vitro by co-labeling cells with SPIO and green fluorescent protein (GFP). MRI experiments were performed on a clinical 3.0T MRI scanner. Two cell-based cartilage repair techniques were mimicked for evaluating MRI traceability of labeled cells: intra-articular cell injection and cell implantation in cartilage defects. Cells were applied ex vivo or in vitro in an intra-articular environment and immediately scanned. SPIO labeling was effective and did not impair any of the studied safety aspects, including hBMSC secretion profile. SPIO from dead, labeled cells could be taken up by synovial cells. Both injected and implanted SPIO-labeled cells could accurately be visualized by MRI in a clinically relevant sized joint model using clinically applied cell doses. Finally, we quantified the amount of labeled cells seeded in cartilage defects using MR-based relaxometry. SPIO labeling appears to be safe without influencing cell behavior. SPIO labeled cells can be visualized in an intra-articular environment and quantified when seeded in cartilage defects.


Chromosome-level assembly of southern catfish (silurus meridionalis) provides insights into visual adaptation to nocturnal and benthic lifestyles.
The Southern catfish (Silurus meridionalis) is a nocturnal and benthic freshwater fish endemic to the Yangtze River and its tributaries. In this study, we constructed a chromosome-level draft genome of S. meridionalis using 69.7-Gb Nanopore long reads and 49.5-Gb Illumina short reads. The genome assembly was 741.2 Mb in size with a contig N50 of 13.19 Mb. An additional 116.4 Gb of Bionano and 77.4 Gb of Hi-C data were applied to assemble contigs into scaffolds and further into 29 chromosomes, resulting in a 738.9-Mb genome with a scaffold N50 of 28.04 Mb. A total of 22,965 protein-coding genes were predicted from the genome with 22,519 (98.06%) genes functionally annotated. Comparative genomic and transcriptomic analyses revealed a rod-dominated visual system which was responsible for scotopic vision. The absence of cone opsins SWS1 and SWS2 resulted in the lack of ultraviolet and blue violet sensitivity. Mutations at key amino acid sites of RH1.1, RH1.2 and RH2 resulted in spectral tuning good for dim light vision and narrow colour vision. A higher expression level of rod phototransduction genes than that of cone genes and higher rod-to-cone ratio led to higher optical sensitivity under dim light conditions. In addition, analysis of the genes involved in eye morphogenesis and development revealed the loss of some conserved noncoding elements, which might be associated with the small eyes in catfish. Together, our study provides important clues for the adaptation of the catfish visual system to the nocturnal and benthic lifestyles. The draft genome of S. meridionalis represents a valuable resource for studies of the molecular mechanisms of ecological adaptation.


Water budgeting in conservation agriculture-based sub-surface drip irrigation in tropical maize using HYDRUS-2D in South Asia.
In water scarce regions of South Asia, diversification of rice with maize is being advocated towards sustainability of cereal-based cropping systems. Adoption of innovative agronomic management practices, i.e., conservation agriculture (CA) and sub-surface drip irrigation (SSDI) are considered as key strategies for much needed interventions to address the challenges of water scarcity under projected climate change. Benefits from CA and SSDI concerning water economy are well-established, however, information about their complementarity and water budgeting in cereal-based systems are lacking. A field study was conducted with process-based model (HYDRUS-2D) to understand water transport, root water uptake and components of soil water balance in maize grown in rotation with wheat after five years of continuous adoption of conservation agriculture. In this study, altogether eight treatments comprising of 6 CA+ treatments (CA coupled with SSDI); permanent beds using sub-surface drip (PB-SSD) with (WR) and without (WOR) crop residue at different N rates, 0, 120 and 150 kg N ha-1 were compared with CA (PB using furrow irrigation-FI with crop residue-120 kg N ha-1) and conventional tillage practices (CT) (CT using FI without crop residue-120 kg N ha-1). Results showed that the model could simulate the daily changes in profile soil water content with reasonable accuracy in all the treatments. Simulated soil water balance indicated higher cumulative root water uptake (CRWU), lower cumulative evaporation (CE) and higher soil water retention in CA+ (PB-SSD+ crop residue at 150 and 120 kg N ha-1) than CA and CT plots. Hydrus-2D model efficiency > 0, RMSE between 0.009-0.026 and R2 value between 0.80-0.92 at P < 0.01 indicates that the model is performing efficiently. The mean evaporation from CA+ treatments was 10 and 36% less than CA and CT treatments, respectively. On average, CRWU under CA+ treatments were 14-48% higher than FI treatments. The mean cumulative deep drainage in CA+ plots was 80-100 mm less than CA and CT plots. In CA+ based plots significantly higher biomass production and radiation use efficiency were observed with reduced water use than CA and CT. Therefore, the study justifies the water-saving nature of CA+, while maintaining higher productivity and meeting the transpiration demand of crops and halting unnecessary evaporation and deep drainage losses.


Comparison study of carbon clusters formation during thermal decomposition of 1,3,5-triamino-2,4,6-trinitrobenzene and benzotrifuroxan: a ReaxFF based sequential molecular dynamics simulation.
Carbon rich clusters are usually found after the detonation of explosives, which greatly hinder their further decomposition into small molecules. A comparison study of thermal decomposition and clusters formation between 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) and benzotrifuroxan (BTF) crystals was conducted to uncover the mechanisms behind their distinct differences in sensitivity and reaction violence, which has not been investigated in detail. The simulations of heating at 3500 K, then expansion and cooling were conducted through reactive molecular dynamics using the ReaxFF-lg force field. As a result, the initial low decay rate indicates that TATB is more stable than BTF under high temperatures, while once ignited it decays faster than BTF. Nevertheless, BTF decomposes more completely with a higher potential energy release, a greater amount of final products, and higher reaction frequencies, and shows higher reaction violence than TATB. More and heavier clusters occur in TATB crystals compared with those in BTF. Large clusters form during the heating process and then partly dissociate during expansion and cooling. A faster cooling rate facilitates larger clusters formation. Graphitic geometries as well as carbon rings and carbon chains are common in the stable clusters. Besides, further simulations show that a lower heating temperature facilitates larger clusters formation both in TATB and BTF. Our results are expected to deepen the insight into the mechanisms of carbon clusters formation and the different performances of TATB and BTF.


Targeting metastatic upper gastrointestinal adenocarcinomas.
Upper gastrointestinal (GI) tumors, including adenocarcinoma of the esophagus, stomach, pancreas, and biliary tree, have traditionally been difficult to treat with cytotoxic chemotherapeutic agents. There has been little drug development success in treating these cancers over the last 20 years, perhaps a reflection of a combination of the aggressive biology of these tumors, the void in effective and specific drug development for these varied tumors, and the lack of properly designed, biologically-based clinical trials. Recently, so called "targeted agents" have risen to the forefront in the care of cancer patients and have made strong impacts in many areas of oncology, particularly gastrointestinal stromal tumors (GIST), colon, breast, and lung cancers. Unfortunately, slow progress has been made using such agents in upper GI tumors. However, more recently, trials in some tumor types have demonstrated gains in progression free survival and overall survival. In this review, we discuss the drugs and pathways that have been most successful in the treatment of upper GI tumors and present the relevant data supporting their use for each tumor site. Additionally, we will explore a few novel pathways that may prove effective in the treatment of upper GI malignancies in the near future.


Response to pain by different gestational age neonates.
One hundred infants were divided into the following 3 gestational age (GA) groups: (I) premature infants (n = 30) with the gestational age between 29 and 32 weeks; (II) premature infants (n = 30) with the gestational age between 33 and 36 weeks; (III) full-term infants (n = 40). The recorded responses of all infants to pain included the behavioral responses to painful stimuli (cry, facial activity and limbs movement) and the variety of heart rate. The results indicated that the infants of 3 groups had different degree response to various painful stimuli. Pain expression in full term infants was more significant than premature infants to same stimuli. 33-weeks GA infants were differential from 29-weeks GA infants. Full term infants showed more vertical mouth stretch and more taut tongue and more hand to mouth than premature infants, but more horizontal mouth stretch in premature infants.


Implants talk to each-other: RF heating changes when two DBS leads are present simultaneously during MRI.
Deep brain stimulation (DBS) has proven to be an effective treatment for Parkinson's disease and other brain disorders. The procedure often involves implanting two elongated leads aimed at specific brain nuclei in both the left and right hemispheres. However, evaluating the safety of MRI in patients with such implants has only been done on an individual lead basis, ignoring the possibility of crosstalk between the leads. This study evaluates the impact of crosstalk on power deposition at the lead tip through numerical simulation and phantom experiments. We used CT images to obtain patient-specific lead trajectories and compared the power deposition at the lead tip in cases with bilateral and unilateral DBS implants. Our results indicate that the RF power deposition at the lead tip can vary by up to 6-fold when two DBS leads are present together compared to when only one lead is present. Experimental measurements in a simplified case of two lead-only DBS systems confirmed the existence of crosstalk.Clinical Relevance-Our results indicate that RF heating of implanted leads during MRI can be affected by the presence of another lead in the body, which may increase or decrease the power deposition in the tissue depending on the position and configuration of the leads.


Neurovascular preservation in orthotopic cystectomy: impact on female sexual function.
The published data regarding female orthotopic cystectomy have focused primarily on urethral recurrence and urinary continence. In a new era of sexuality, evaluating postoperative sexual outcome has become a new surgical endpoint. In this study, we focused on the impact of neurovascular preservation after radical cystectomy and neobladder construction. We assessed female sexuality in 13 patients after orthotopic cystectomy using a standardized questionnaire, Female Sexual Function Index (FSFI). Six patients had undergone nerve-sparing cystectomy and seven had undergone contemporary non-nerve-sparing cystectomy. Intraoperatively, the tumor was deemed oncologically safe for neurovascular preservation. All 13 patients were sexually active preoperatively, were younger than 65 years old, had recurrence-free follow-up findings after 1 year, and had undergone no pelvic irradiation. The 19-item FSFI questionnaire analyzed six domains (desire, arousal, lubrication, orgasm, satisfaction, and pain) of sexual function. In the nerve-sparing group (mean age 55.9 years), the baseline and 12-month postoperative scores showed a minimal decline in results, with a total mean FSFI score of 24.5 versus 22.3, respectively. In analyzing each of the six domains, no significant decline or difference was observed. Conversely, in the non-nerve-sparing group (mean age 56.7 years), a significant decline or difference was found in the 12-month total mean FSFI scores between the baseline and postoperative FSFI scores (25.0 versus 11.0, respectively). In the non-nerve-sparing group, 6 of 7 patients ultimately discontinued sexual intercourse. Female sexual function was preserved in patients who received neurovascular preservation. In contrast, all domains of sexual function declined in patients who had undergone non-neurovascular preservation.


Genetic polymorphism in muscle biopsies of Duchenne and Becker muscular dystrophy patients.
Duchenne muscular dystrophy (DMD), with an incidence of one in 3500 male new borns, and its milder variant, Becker muscular dystrophy (BMD), are allelic X-linked recessive disorders, caused by mutations in the gene coding for dystrophin, a 427 kD cytoskeleton protein. There are no available molecular markers to differentiate these two. The purpose of this study was to study genetic polymorphism in muscular dystrophy and explore its potential in discriminating these two allelic forms of the disease. The results revealed unambiguously the presence of three transcripts : 598bp, 849bp and 1583bp long which are selectively expressed in the muscles afflicted with muscular dystrophy as compared to the normal muscle. 1583bp gene transcript was conspicuously present in the muscle tissues of both DMD and BMD patients whereas 598bp and 849bp long transcripts were exclusively present in DMD but not in BMD patients or normal human subjects. These gene transcripts had no sequence homology with dystrophin gene and these were also present in the families belonging to DMD and BMD patients. These results point to the fact that based upon the selective expression of these three gene transcripts, one could not only differentiate between DMD and BMD diseases at the molecular level, but also between normal and dystrophic muscle. Further, these findings also reveal that apart from dystrophin gene, these gene transcripts may also be responsible for the differential progression of DMD/BMD phenotype.


Observation of ferromagnetic resonance in SrRuO3 by the time-resolved magneto-optical Kerr effect.
We report the observation of ferromagnetic resonance (FMR) in SrRuO3 using the time-resolved magneto-optical Kerr effect. The FMR oscillations in the time-domain appear in response to a sudden, optically induced change in the direction of easy-axis anisotropy. The high FMR frequency, 250 GHz, and large Gilbert damping parameter, alpha approximately 1, are consistent with strong spin-orbit coupling. We find that the parameters associated with the magnetization dynamics, including alpha, have a nonmonotonic temperature dependence, suggestive of a link to the anomalous Hall effect.


Explaining the negative impact of workplace incivility on work and non-work outcomes: The roles of negative rumination and organizational support.
Research studies have shown that workplace incivility is associated with numerous negative work and non-work outcomes. The underlying mechanisms explaining why workplace incivility is associated with these outcomes, as well as contextual buffers of these relationships, have received less attention. This study extends workplace incivility research by examining the mediating role of negative rumination as a potential factor undergirding the relationship between experiences of incivility from colleagues at work and detrimental outcomes. We also investigated perceived organizational support and family supportive work environment as potential mitigators of the indirect relationship between incivility and negative outcomes. Data were collecfrom 154 university faculty members on two occasions. The results showed that negative rumination mediated the relationships between workplace incivility and both work (job satisfaction, burnout) and non-work (work-to-family conflict, life satisfaction) outcomes. Furthermore, results from the moderated mediation analyses revealed that perceived organizational support buffered the mediated effect of negative rumination and job satisfaction and a family-supportive work environment buffered the mediated effect of negative rumination on work-to-family conflict. Overall, the results demonstrate that negative rumination helps explain why workplace incivility negatively affects both work and non-work outcomes and underscores the important role of organizational context as buffers for these relationships.


Parathyroid hormone and heart failure: novel biomarker strategy.
Heart failure (HF) is a clinical syndrome featuring cardiac pump failure along with signs and symptoms arising from salt and water retention mediated by activated renin-angiotensin-aldosterone system (RAAS). In addition to this cardiorenal perspective, HF is accompanied by a systemic illness, especially in advanced stages characterized by oxidative stress in various tissues, causing damage to soft tissue and bone. Secondary hyperparathyroidism (SHPT) which is also considered to contribute this systemic illness is therefore prominent in advanced HF. SHPT in HF occurs as a result of RAAS activation, prominent hyperaldosteronism, loop diuretic usage and decreased calcitriol level, all of which results in calcium excretion. We review the evidence that high parathyroid hormone (PTH) is associated with advanced HF, as well as evidence that it's associated with HF with preserved ejection fraction (HFPEF).


Effective block scheduling strategies.
The scheduling of surgery provides opportunities to orchestrate a wide variety of resources that have a significant impact on both hospitals, physicians, and patients. This article presents the successful development and implementation of a block scheduling system in a large operating room setting. Strategies include process redesign, automation, and physician empowerment to achieve outcomes of improved efficiency, customer satisfaction and physician self-governance.


Increased stress and effectiveness of placebos and "active" drugs.
Evidence is presented to indicate that placebos are far more effective in producing carefully defined relief of pathological pain than they are in the case of experimental pain. This is construed as further support for the view that placebos are more effective when stress is great than they are when stress is not so great. A similar situation holds for morphine. Certain drugs are effective in relieving visceral sensations only if an essential psychological state is present. This is, in effect, a new principle of drug action.


Bereavement care immediately after perinatal loss in health care facilities: a scoping review protocol.
This scoping review will summarize what is known about formal and informal perinatal bereavement care guidelines used in health care facilities before discharge, and map the mental health outcomes of parents against characteristics of the guidelines. Conflicting evidence for bereavement care guidelines, the lack of randomized controlled trials and experimental studies, and older synthesized information with a limited focus or population make synthesis complex. A scoping review will help determine the breadth and depth of the literature. Sources pertaining to bereavement care guidelines used in health care facilities immediately after perinatal loss (miscarriage, stillbirth, or neonatal death) and measuring parents' mental health outcomes will be included. Sources relating to family members other than parents, perinatal loss occurring outside of a health care facility, and physical care guidelines will be excluded. The proposed review will be conducted using the JBI methodology for scoping reviews. The team will consider quantitative and qualitative studies, practice guidelines, case reports, expert opinions, systematic reviews, professional organization websites, and gray literature. Databases to be searched will include CINAHL, PsycINFO, SocINDEX, Cochrane Library, Embase, MEDLINE, and Web of Science. The earliest empirical study found (1976) will serve as the starting date limit. After pilot testing, the two-step screening process (titles and abstracts, then full-text articles), data will be extracted, collated, and presented in narrative form as well as in tables and diagrams. The results will provide facilities with a broad view of bereavement care to support grieving parents' mental health.


Recipients of supplemental security income and the student earned income exclusion.
This article presents the results of a first effort to create and statistically analyze a data set containing detailed information on the Student Earned Income Exclusion (SEIE), which is part of the Supplemental Security Income (SSI) program. It presents descriptive statistics on (1) demographic characteristics of SSI recipients with SEIE; (2) various measures of SEIE use, such as dollar amounts excluded per year, numbers of months of use per year, and percentages of SSI recipients using the SEIE; (3) seasonal patterns in SEIE use based on month-by-month SEIE amounts; and (4) seasonal patterns in factors driving month-by-month gains and losses of SEIE eligibility, including changes in earnings, student status, age, and eligibility for SSI, as well as effects of the annual SEIE limit.


Berberine, a natural alkaloid sensitizes human hepatocarcinoma to ionizing radiation by blocking autophagy and cell cycle arrest resulting in senescence.
To study the radiosensitizing potential of Berberine and the underlying mechanism in human hepatocarcinoma (HepG2) cells. HepG2 cells were challenged with X-rays in combination with Berberine treatment and several in vitro assays were performed. Alteration in cell viability was determined by MTT assay. Changes in intracellular ROS levels, mitochondrial membrane potential/mass, intracellular acidic vesicular organelles as well as cell cycle arrest and apoptotic cell death were analysed by flow cytometry. Induction of autophagy was assessed by staining the cells with Monodansylcadaverine/Lysotracker red dyes and immunoblotting for LC3I/II and p62 proteins. Phase-contrast/fluorescence microscopy was employed to study mitotic catastrophe and senescence. Cellular senescence was confirmed by immunoblotting for p21 levels and ELISA for Interleukin-6. X-rays + Berberine had a synergistic effect in reducing cell proliferation accompanied by a robust G2/M arrest. Berberine-mediated radiosensitization was associated with elevated levels of LC3II and p62 suggesting blocked autophagy that was followed by mitotic catastrophe and senescence. Treatment of cells with X-rays + Berberine resulted in increased oxidative stress, hyperpolarized mitochondria with increased mitochondrial mass and reduced ATP levels. The study expands the understanding of the pharmacological properties of Berberine and its applicability as a radiosensitizer towards treating liver cancer.


Deep brain stimulation in the treatment of obesity.
Obesity is a growing global health problem frequently intractable to current treatment options. Recent evidence suggests that deep brain stimulation (DBS) may be effective and safe in the management of various, refractory neuropsychiatric disorders, including obesity. The authors review the literature implicating various neural regions in the pathophysiology of obesity, as well as the evidence supporting these regions as targets for DBS, in order to explore the therapeutic promise of DBS in obesity. The lateral hypothalamus and ventromedial hypothalamus are the appetite and satiety centers in the brain, respectively. Substantial data support targeting these regions with DBS for the purpose of appetite suppression and weight loss. However, reward sensation associated with highly caloric food has been implicated in overconsumption as well as obesity, and may in part explain the failure rates of conservative management and bariatric surgery. Thus, regions of the brain's reward circuitry, such as the nucleus accumbens, are promising alternatives for DBS in obesity control. The authors conclude that deep brain stimulation should be strongly considered as a promising therapeutic option for patients suffering from refractory obesity.


Chemotaxis, spreanding nd oxidative metabolism of neutrophils: influence of albumin in vitro.
Studies on polymorphonuclear leukocyte (PMN) migration in vitro have shown that albumin increases the speed of the cells without affecting their orientation, i. e. chemokinesis. In order to analyze this phenomenon the effect of albumin on PMN migration in a Boyden chamber towards various chemotactic agents was examined. On attraction with low molecular weight chemotactic factors (a culture filtrate of E. coli (BCF)) or the synthetic peptide N-Formyl-Methionyl-Leucyl-Phenylalanine (F-Met-Leu-Phe) albumin enhanced the migration of PMN. In contrast, albumin did not enhance the migration towards casein, a high molecular weight chemotactic factor, except at very low concentrations. In a direct visual assay, albumin was found to impair PMN spreading on a polystyrene Petri dish. In the presence of BCF or F-Met-Leu-Phe cell spreading remained inversely related to the concentration of albumin, while addition of casein again eliminated the influence of albumin. The effect of albumin on the interaction of PMN with a substrate was studied by measuring the superoxide anion (02-) release by PMN sedimenting on a micropore filter. The 02- release triggered by this stimulus of the PMN membrane was inversely correlated to the concentration of albumin. These results show that one mechanism of the enhancing effect of albumin on PMN migration is to diminish adhesion of the cells to the substratum, so that it remains reversible. It is suggested that the term chemokinesis is equivocal. The chemokinetic activity of chemotactic factors would be the result of specific stimulation of PMN locomotion. In contrast, the chemokinetic activity of albumin is due to changes of the physico-chemical environment which support PMN locomotion.


Some mullerian inclusion cysts in lymph nodes may sometimes be metastases from serous borderline tumors of the ovary.
Glandular inclusions that appear morphologically benign are occasionally found in lymph nodes as well as in peritoneal and omental biopsies. In patients with gynecologic malignancies, the nature and significance of these mullerian inclusion cysts (MIC) present a diagnostic challenge with regard to whether they are benign and incidental or are related to the coincident tumor for which surgery is being performed. Sixty-two cases of MIC were prospectively identified during a 6-year period. The frequencies were calculated and stratified by lymph node chain distribution, primary tumor site, and primary tumor type. MIC appeared as small cysts lined by a serous (mullerian)-type, cytologically bland, cuboidal to columnar epithelium with a simple architecture. Among 62 women, MIC was found in lymph nodes (27 cases), pelvic peritoneum (19 cases), omentum (16 cases), bowel serosa (9 cases), uterine serosa (8 cases), and parametrial connective tissues (4 cases). Among a set of 417 consecutive cases in which lymphadenectomy was performed, 46 (11%) women had MIC. The MIC involved multiple sites (26 cases in the peritoneum/omentum and 27 in lymph nodes). The primary tumor was in the ovary in 32 of the 46 women with MIC (70%) and of these, 17 were borderline serous (53%). Sixty-two of 6,154 lymph nodes examined contained MIC (1.0%). 3.2% of nodes contained MIC in which the primary tumor arose in the ovary, but only 0.1% with either endometrial or cervical tumors (chi2, p <0.00001). The lymph nodes most often involved by MIC were from para-aortic sites (40%), which reflect the primary drainage route from the ovary. Not uncommonly, neighboring areas in the same lymph node group with MIC disclosed separate foci of obvious metastatic borderline tumor (4 of 10; 40%). In summary, the increased frequency of MIC in lymph nodes sampled for primary ovarian malignancies suggests that MIC in some cases, rather than being benign, incidental inclusions, are more likely bland-appearing forms of metastatic tumor. The preponderance of inclusions occurs with serous ovarian tumors of borderline malignancy, and the inclusions are overrepresented in the lymph nodes that primarily receive drainage from the ovary.


Multi-task Model for Glioma Segmentation and Isocitrate Dehydrogenase Status Prediction Using Global and Local Features.
According to the 2021 World Health Organization IDH status prediction scheme for gliomas, isocitrate dehydrogenase (IDH) is a particularly important basis for glioma diagnosis. In general, 3D multimodal brain MRI is an effective diagnostic tool. However, only using brain MRI data is difficult for experienced doctors to predict the IDH status. Surgery is necessary to be performed for confirming the IDH. Previous studies have shown that brain MRI images of glioma areas contain a lot of useful information for diagnosis. These studies usually need to mark the glioma area in advance to complete the prediction of IDH status, which takes a long time and has high computational cost. The tumor segmentation task model can automatically segment and locate the tumor region, which is exactly the information needed for the IDH prediction task. In this study, we proposed a multi-task deep learning model using 3D multimodal brain MRI images to achieve glioma segmentation and IDH status prediction simultaneously, which improved the accuracy of both tasks effectively. Firstly, we used a segmentation model to segment the tumor region. Also, the whole MRI image and the segmented glioma region features as the global and local features were used to predict IDH status. The effectiveness of the proposed method was validated via a public glioma dataset from the BraTS2020. Our experimental results show that our proposed method outperformed state-of-the-art methods with a prediction accuracy of 88.5% and average dice of 79.8%. The improvements in prediction and segmentation are 3% and 1% compared with the state-of-the-art method, respectively.


Comparison of the Type of Fixation of Akin Osteotomy.
The objective of the study was to assess the influence of the type of fixation of the Akin osteotomy when used during hallux valgus surgery. Between 2013 and 2016, we performed 138 Akin osteotomy procedures employing a staple (group A, 43 patients), screw (group B, 47 patients), and single or double transosseous suture stabilization (group C, 48 patients). We assessed the pre- and postoperative interphalangeal angle (IPA), hallux valgus angle (HVA), and intermetatarsal angle (IMA) on dorsoplantar and lateral foot weightbearing x-rays and used the American Orthopaedic Foot & Ankle Society (AOFAS) hallux-metatarsophalangeal-interphalangeal scale for preoperative and 12-month postoperative follow-up clinical assessment. All the complications and costs of implant usage were recorded. In all the groups, the average HVA (A: from 33.4 to 13.1 degrees; B: from 32.8 to 14.1 degrees; C: from 31.9 to 12.9 degrees), IMA (A: from 14.4 to 7.2 degrees; B: from 13.9 to 6.9 degrees; C: from 14.5 to 7.1 degrees), and IPA (A: from 12.1 to 5.6 degrees; B: from 11.7 to 6.0 degrees; C: from 12.5 to 5.9 degrees) decreased. The average AOFAS score improved in groups A (from 45 to 91 points), B (from 42 to 90 points), and C (from 42 to 91 points). We observed 1 recurrence after the single-tunnel suture fixation, 1 prominent screw, and 1 staple soft tissue irritation. We did not find a delayed union or nonunion. The suture fixation of the Akin osteotomy provides results comparable to other forms of stabilization. The procedure is cost saving and helps to avoid hardware-related complications. Despite the type of bunion surgery used, fixation of the Akin osteotomy with suture was as good as more expensive and potentially more complicated fixation methods. Level III, retrospective comparative study.


Oncological and quality of life outcomes following extralevator versus standard abdominoperineal excision for rectal cancer.
INTRODUCTION There is increasing and conflicting research debating the oncological benefits of extralevator abdominoperineal excision (ELAPE) compared with standard abdominoperineal excision (SAPE). However, there is very little in the literature on the long-term effects on patients' wellbeing following the two procedures. The aim of this study was to determine the oncological outcomes and long-term quality of life (QoL) of patients at two hospitals having undergone ELAPE or SAPE. METHODS Consecutive patients with rectal cancer who underwent either ELAPE or SAPE between January 2009 and June 2015 at a single centre were analysed. Oncological outcomes were determined by histology and follow-up imaging. QoL data were obtained prospectively using the QLQ-C30 and QLQ-CR29 questionnaires. RESULTS A total of 48 patients (36 male, 12 female; 27 ELAPE, 21 SAPE) were reviewed. The mean age was 67.4 years and the median follow-up duration was 44 months (range: 6-79 months). Four patients (2 ELAPE, 2 SAPE) developed local recurrence. Rates of distant metastasis were similar (ELAPE: 11%, SAPE: 14%). There was no significant difference in mean global health status score (ELAPE: 77.3, SAPE: 65.3). Impotence was the most frequently reported problem (mean symptom scores of 89.7 and 78.8 for ELAPE and SAPE respectively). CONCLUSIONS This is the largest study with the longest follow-up period that compares QoL after ELAPE with that after SAPE. Although more radical in nature, ELAPE did not demonstrate any significant impact on QoL compared with SAPE. There was no significant difference in long-term oncological outcome between the groups. Impotence remains a significant problem for all patients and they should be well informed of this risk prior to surgery.


Liver disease and malnutrition.
Patients with hepatic disorders are exceptionally vulnerable to developing malnutrition because of the key role played by the liver in regulating the nutritional state and the energy balance. Moreover, the presence of chronic liver disorders could reduce the appetite and thus influence the nutrient intake. Poor nutritional status has been shown in various patient groups with hepatic disorders, and particularly in patients with alcoholic cirrhosis who are at high nutritional risk. It is well established that malnourished patients with liver diseases generally have a higher risk of developing adverse clinical outcomes and increased healthcare costs. Nutrition screening with the Subjective Global Assessment and anthropometric measurements are an important first step in the early identification of malnutrition and initiates the whole nutrition care process. It is therefore important for appropriate nutrition policies and protocols to be implemented so that all patients with chronic liver diseases are monitored closely from a nutritional standpoint. Early and evidence-based nutritional interventions are eagerly needed to minimize the nutritional decline associated with chronic liver disorders and ultimately improve the prognosis of such patients. This review includes a comprehensive analysis of methods to identify malnutrition in patients with chronic liver diseases as well as the extent and impact of the malnutrition problem in selected patient populations.


Recombinant Bombyx mori nucleopolyhedrovirus harboring green fluorescent protein.
The gene encoding the green fluorescent protein (gfp) under the control of the highly expressed Autographa californica nucleopolyhedrovirus (AcMNPV)-polyhedrin promoter has been introduced into the polyhedrin (polh) locus of Bombyx mori nucleopolyhedrovirus (BmNPV) by homologous recombination. The insect host larvae and the cultured cells infected with this recombinant virus (vBmGFP) showed high levels of expression of gfp. The larval tissues permissive to virus multiplication could be readily visualized using the tagged recombinant virus, thus providing a direct approach to study the progress of virus infection or its control in the animal host. The highly expressed recombinant protein, GFP, could be easily solubilized from fat bodies. Thus, the caterpillar-based expression could serve as an economic alternative method for the large-scale production of recombinant proteins, even when they are nonsecretory in nature. Further, if the recombinant vBmGFP is used as a parent in generating other recombinants, conversion of the fluorescent plaques to colorless plaques serves as an easy means for screening recombinants. Such a method is especially helpful for BmNPV-recombinant selections in the absence of the other simplified techniques as are available for the prototype baculovirus AcMNPV system.


Fluorination Induced Donor to Acceptor Transformation in A1-D-A2-D-A1-Type Photovoltaic Small Molecules.
With the development of diversity of non-fullerene acceptors, it is found that there is no clear boundary between electron donors and electron acceptors. Modulation of the electron donating and withdrawing properties of organic semiconductors is necessary for organic photovoltaics research. In this work, we designed and synthesized three A1-D-A2-D-A1-type (A represents acceptor unit and D represents donor unit) small molecules, named as M-0F, M-1F, and M-2F, respectively containing zero, one, and two fluorine atoms in the terminal acceptor segments (A1), respectively. Fluorination substitution was found to be able to downshift the HOMO and LUMO energy level, red-shift the absorption, and enhance the electron mobility. The M-0F exhibited the highest efficiency of 5.99% as a donor in fullerene-containing system and the lowest efficiency of 0.58% as an acceptor in fullerene-free system. While the M-2F performed the lowest efficiency of 0.97% as the donor and the highest efficiency of 2.65% as the acceptor. The electron-donating and electron-withdrawing property of M-1F are in-between that of M-0F and M-2F. Among the three molecules, the electron mobility is increased while the hole mobility is decreased with increasing fluorination. This work provides a typical example of tuning of the electron donating and withdrawing property without changes to the backbone of the conjugated molecules, which is important for further designing high performance solution processable small molecules.


Ionic cluster size distributions of swollen nafion/sulfated beta-cyclodextrin membranes characterized by nuclear magnetic resonance cryoporometry.
Nafion/sb-CD membranes were prepared by mixing 5 wt% Nafion solution with H+-form sulfated beta-cyclodextrin (sb-CD), and their water uptakes, ion exchange capacities (IECs), and ionic cluster size distributions were measured. Gravimetric and thermogravimetric measurements showed that the water uptake of the membranes increased with increases in their sb-CD content. The IECs of the membrane were measured with acid-base titration and found to increase with increases in the sb-CD content, reaching 0.96 mequiv/g for NC5 ("NCx" denotes a Nafion/sb-CD composite membrane containing x wt% of sb-CD). The cluster-correlation peaks and ionic cluster size distributions of the water-swollen membranes were determined using small-angle X-ray scattering (SAXS) and 1H nuclear magnetic resonance (NMR) cryoporometry, respectively. The SAXS experiments confirmed that increases in the sb-CD content of the membranes shifted the maximum SAXS peaks to lower angles, indicating an increase in the cluster correlation peak. NMR cryoporometry is based on the theory of the melting point depression, Delta Tm, of a liquid confined within a pore, which is dependent on the pore diameter. The melting point depression was determined by analyzing the variation of the NMR signal intensity with temperature. Our analysis of the intensity-temperature (IT) curves showed that the ionic cluster size distribution gradually became broader with increases in the membrane sb-CD content due to the increased water content, indicating an increase in the ionic cluster size. This result indicates that the presence of sb-CD with its many sulfonic acid sites in the Nafion membranes results in increases in the ionic cluster size as well as in the water uptake and the IEC. We conclude that NMR cryoporometry provides a method for determining the ionic cluster size on the nanometer scale in an aqueous environment, which cannot be obtained using other methods.


Post-2020 biodiversity targets need to embrace climate change.
Recent assessment reports by the Intergovernmental Panel on Climate Change (IPCC) and the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) have highlighted the risks to humanity arising from the unsustainable use of natural resources. Thus far, land, freshwater, and ocean exploitation have been the chief causes of biodiversity loss. Climate change is projected to be a rapidly increasing additional driver for biodiversity loss. Since climate change and biodiversity loss impact human societies everywhere, bold solutions are required that integrate environmental and societal objectives. As yet, most existing international biodiversity targets have overlooked climate change impacts. At the same time, climate change mitigation measures themselves may harm biodiversity directly. The Convention on Biological Diversity's post-2020 framework offers the important opportunity to address the interactions between climate change and biodiversity and revise biodiversity targets accordingly by better aligning these with the United Nations Framework Convention on Climate Change Paris Agreement and the Sustainable Development Goals. We identify the considerable number of existing and proposed post-2020 biodiversity targets that risk being severely compromised due to climate change, even if other barriers to their achievement were removed. Our analysis suggests that the next set of biodiversity targets explicitly addresses climate change-related risks since many aspirational goals will not be feasible under even lower-end projections of future warming. Adopting more flexible and dynamic approaches to conservation, rather than static goals, would allow us to respond flexibly to changes in habitats, genetic resources, species composition, and ecosystem functioning and leverage biodiversity's capacity to contribute to climate change mitigation and adaptation.


A new approach to assess occupational exposure to airborne fungal contamination and mycotoxins of forklift drivers in waste sorting facilities.
The waste management industry is an important employer, and exposure of waste-handling workers to microorganisms is considered an occupational health problem. Besides fungal contamination, it is important to consider the co-occurrence of mycotoxins in this setting. Forklifts with closed cabinet and air conditioner are commonly used in waste industry to transport waste and other products within the facilities, possibly increasing the risk of exposure under certain conditions. The aim of this study was to assess the fungal contamination and mycotoxin levels in filters from the air conditioning system of forklift cabinets, as an indicator to assess occupational exposure of the drivers working in a waste sorting facility. Cytotoxicity was also assessed to understand and characterize the toxicity of the complex mixtures as present in the forklift filters. Aqueous extracts of filters from 11 vehicles were streaked onto 2% malt extract agar (MEA) with chloramphenicol (0.05 g/L) media, and in dichloran glycerol (DG18) agar-based media for morphological identification of the mycobiota. Real-time quantitative PCR amplification of genes from Aspergillus sections Fumigati, Flavi, Circumdati, and Versicolores was also performed. Mycotoxins were analyzed using LC-MS/MS system. Cytotoxicity of filter extracts was analyzed by using a MTT cell culture test. Aspergillus species were found most frequently, namely Aspergillus sections Circumdati (MEA 48%; DG18 41%) and Nigri (MEA 32%; DG18 17.3%). By qPCR, only Aspergillus section Fumigati species were found, but positive results were obtained for all assessed filters. No mycotoxins were detected in aqueous filter extracts, but most extracts were highly cytotoxic (n = 6) or medium cytotoxic (n = 4). Although filter service life and cytotoxicity were not clearly correlated, the results suggest that observing air conditioner filter replacement frequency may be a critical aspect to avoid worker's exposure. Further research is required to check if the environmental conditions as present in the filters could allow the production of mycotoxins and their dissemination in the cabinet during the normal use of the vehicles.


Electron transfer flavoprotein from Methylophilus methylotrophus: properties, comparison with other electron transfer flavoproteins, and regulation of expression by carbon source.
When grown on methylated amines as a carbon source, Methylophilus methylotrophus synthesizes an electron transfer flavoprotein (ETF) which is the natural electron acceptor of trimethylamine dehydrogenase. It is composed of two dissimilar subunits of 38,000 and 42,000 daltons and 1 mol of flavin adenine dinucleotide. It was reduced by trimethylamine dehydrogenase to a stable anionic semiquinone form, which could not be converted, either enzymatically or chemically, to the fully reduced dihydroquinone. This ETF exhibited spectral properties which were nearly identical to ETFs from bacterium W3A1, Paracoccus denitrificans, and pig liver mitochondria. M. methylotrophus ETF cross-reacted immunologically and enzymatically with the ETF of bacterium W3A1 but not with the other two ETFs. In M. methylotrophus and bacterium W3A1, ETF and trimethylamine dehydrogenase were each expressed during growth on trimethylamine and were each absent during growth on methanol.


Histone molar ratios among different electrophoretic forms of mono- and dinucleosomes.
The relative molar ratios of each of the histone classes and protein A24 have been determined in nuclei, chromatin, and different electrophoretic forms of mono- and dinucleosomes of cultured mouse cells. For this purpose, [3H]lysine- and [14C]arginine-labeled cells were used for sample preparations, and stoichiometries were estimated from protein radioactivity profiles and known amino acid compositions following sodium dodecyl sulfate (SDS)-gel electrophoresis. The results demonstrate that upper limits of one and two histone H1 molecules exist per mono- and dinucleosome, respectively. However, isolated nuclei contain less than one copy of histone H1 per nucleosome. In addition, among the chromatin subfractions studied, histones H3, H2B, and H4 are essentially equimolar, while histone H2A is less than equimolar by 19 +/- 9%. This latter finding offers direct support to the proposal of Goldknopf (Goldknopf, I. L., French, M. F., Musso, R., and Busch, H. (1977) Proc. Natl. Acad. Sci. U. S. A. 74, 5492-5495) that protein A24 replaces histone H2A in the octamer protein core of the nucleosome, since about 10% of the total histone H2A of cultured mouse cells is in the form of protein A24 and is present in nucleosomes. From the results of the present study, it is concluded that electrophoretic fractionation of mono- and dinucleosomes is not due to variable molar ratios or amounts of the four smaller histone classes, but depends on part on DNA length, the number of associated histone H1 molecules, and non-histone chromosomal proteins.


Good Visual Outcomes After Pituitary Tumor Surgery Are Associated With Increased Visual Cortex Functional Connectivity.
Patients presenting with visual impairment secondary to pituitary macroadenomas often experience variable recovery after surgery. Several factors may impact visual outcomes including the extent of neuroaxonal damage in the afferent visual pathway and cortical plasticity. Optical coherence tomography (OCT) measures of retinal structure and resting-state functional MRI (rsfMRI) can be used to evaluate the impact of neuroaxonal injury and cortical adaptive processes, respectively. The purpose of this study was to determine whether rsfMRI patterns of functional connectivity (FC) distinguish patients with good vs poor visual outcomes after surgical decompression of pituitary adenomas. In this retrospective cohort study, we compared FC patterns between patients who manifested good (GO) vs poor (PO) visual outcomes after pituitary tumor surgery. Patients (n = 21) underwent postoperative rsfMRI a minimum of 1 year after tumor surgery. Seed-based connectivity of the visual cortex (primary [V1], prestriate [V2], and extrastriate [V5]) was compared between GO and PO patients and between patients and healthy controls (HCs) (n = 19). Demographics, visual function, and OCT data were compared preoperatively and postoperatively between patient groups. The threshold for GO was visual field mean deviation equal or less than -5.00 dB and/or visual acuity equal to or better than 20/40. Increased postoperative FC of the visual system was noted for GO relative to PO patients. Specifically, good visual outcomes were associated with increased connectivity of right V5 to the bilateral frontal cortices. Compared with HCs, GO patients showed increased connectivity of V1 and left V2 to sensorimotor cortex, increased connectivity of right and left V2 to medial prefrontal cortex, and increased connectivity of right V5 the right temporal and frontal cortices. Increased visual cortex connectivity is associated with good visual outcomes in patients with pituitary tumor, at late phase of recovery. Our findings suggest that rsfMRI does distinguish GO and PO patients after pituitary tumor surgery. This imaging modality may have a future role in characterizing the impact of cortical adaptation on visual recovery.


Impact of de novo everolimus-based immunosuppression on incisional complications in heart transplantation.
The mammalian target of rapamycin inhibitor sirolimus has been associated with an increased incidence of wound-healing complications after de novo heart transplantation. To evaluate the possibility of a similar association for everolimus, we performed a risk-factor analysis to compare the incidence of incision-related wound complications for everolimus with that of other adjunctive drugs. Safety data from 1009 heart transplant recipients (n=214, receiving azathioprine; n=84, mycophenolate mofetil (MMF); n=711, everolimus) were reviewed in a post hoc analysis from three randomized, multicenter studies-B253 (n=634), A2403 (n=199), and A2411 (n=176)-in which de novo patients received fixed-dose or concentration-controlled everolimus (target trough, 3-8 ng/mL), azathioprine, or MMF with standard- or reduced-exposure cyclosporine A. Incisional complications were analyzed for incidence, type, and severity up to day 90 posttransplant. Incisional-complication events occurred in 25 (11.7%) azathioprine, six (7.2%) MMF, and 87 (12.3%) everolimus patients. Serious incisional complications were more frequent with everolimus (6.9%) compared with azathioprine (4.2%; P=0.197) or MMF (1.2%; P=0.051). In a univariate analysis, patient sex, body mass index (BMI), and diabetes were associated with incisional complications. Only BMI was significantly associated with incisional complications in the subsequent multivariate analysis, with the odds of an incisional-complication event increasing by 12.9% for every 1 kg/m increase in BMI (P<0.001). The incidence of incisional complications with everolimus was generally low, although numerically higher compared with MMF. Our analyses provided no strong evidence that everolimus is an independent risk factor for incisional complications. After de novo heart transplantation, patients with a high BMI are at higher risk of incision-related wound complications.


Urinary lithiasis and urinary tract malformations in children: a retrospective study of 34 cases.
Although the association of urinary lithiasis and urinary tract malformation is not rare, their management poses challenges. The aim of this study was to evaluate the relationship between urolithiasis and malformations of the urinary system. There were 34 patients (19 males and 15 females) with a mean age of 4.8 years (range, 2 months to 14 years). All patients had urinary lithiasis with a urinary tract malformation. Abdominal pain was the most frequent clinical symptom (38%). Urinary infection was found in 7 patients (21%) and macroscopic haematuria was present in 10 patients (29%). The most frequent urinary tract malformations were megaureter (8 cases), uretero-pelvic junction obstruction (7 cases) and vesico-ureteric reflux (8 cases), but its malformative origin could not be confirmed. Treatment consisted of lithiasis extraction in 32 cases associated with specific treatment of the uropathy in 27 cases. Postoperative outcome was uneventful in all cases. In fact, urinary lithiasis and urinary tract malformation association is not rare. Indeed, 9-34% of urinary lithiasis are noted to be associated with urinary tract malformation. Positive diagnosis relies specifically on kidney ultrasound, intravenous urography, and urethrocystography. Treatment depends on the type of urinary tract malformation, localisation and size of the urinary lithiasis. In conclusion, urinary lithiasis and urinary tract malformation association is a frequent eventuality. Surgical intervention is the usual mode of treatment.


Plasma factor XIII and some other haemostasis parameters in patients with diabetic angiopathy.
Since intravascular and endoparietal fibrin deposition is thought to be involved in the development of atherosclerosis, we measured factor XIII activity and its subunit 'a' and 'b' concentrations against a background of other haemostasis parameters in diabetics with angiopathy and in 2 control groups (healthy subjects and diabetics without vascular complications). Diabetics with angiopathy revealed a significant increase of factor XIII activity as well as its subunit concentrations. They also had significantly elevated anti-thrombin III, alpha 2 macroglobulin, alpha 1 antitrypsin, C1 inhibitor, fibrinogen, FDP concentrations and prolongation of euglobulin lysis time. The highest factor XIII levels were found in diabetics with renal failure. We suppose that increased factor XIII level and other observed changes of haemostasis in patients with diabetic angiopathy might promote intravascular and endoparietal fibrin deposition and contribute to the development of atherosclerotic complications of diabetes.


Long-term outcome after sequential resections of liver and lung metastases from colorectal carcinoma.
Surgical resection of colorectal liver metastases (CLM) is an established form of treatment. Limited data exists on the value of sequential hepatic and pulmonary metastasectomy. We analysed patients who underwent sequential liver and lung resections for CLM. A total of 910 patients who underwent liver resection for CLM between January 2000 and December 2007, were analysed to identify patients with resectable pulmonary metastases (n= 43; 4.7%). Patient demographics, overall survival and survival difference between synchronous and metachronous pulmonary metastasectomy groups were compared. In addition, outcomes in the 'liver and lung resection' group were compared with a matched group of 'liver resection only' patients (matched for age, primary disease stage, interval to liver resection and liver disease stage). Forty-three patients (median age 62, range 43-83 years, 22 males) underwent sequential liver and lung resection. A total of 36 patients underwent major hepatic resections, 18 patients had bilobar disease and the median number of liver lesions resected was 3 (range 1-5 lesions). Ten patients had synchronous liver and lung metastases. The median interval between liver and lung metastasectomy was 25 months (range 2-88 months). A total of two patients underwent major lobectomies, three patients had bilateral disease and the median number of lung lesions resected was one (range 1-3). The 1-, 3- and 5-year overall survival rates after first metastasectomy were 100%, 87.1% and 53.9%, respectively, with a median survival of 42 months. Undergoing metachronous pulmonary metastasectomy had better 1-, 3- and 5-year survival rates than those with synchronous disease (100%, 88.9% and 60.9% vs. 100%, 75% and 0%, respectively; P= 0.02, log rank test). There was no significant survival difference between the 'liver and lung resection' and the 'liver resection only' groups. Sequential liver and lung resection for CLM is associated with good long-term survival in selected patients, except in those presenting with synchronous lung and liver metastases.


Treatment of severe hypercholesterolaemia by LDL-apheresis.
The most severe forms of hypercholesterolaemia scarcely respond to diet and conventional drugs administration and need, therefore, alternative treatments. Terapeutic Plasma Exchange demonstrated an improved survival of subjects with Familial Hypercholesterolaemia (FH) in spite of its limitations. Semi-selective and selective techniques have been developed in order to remove LDL cholesterol alone. We studied the efficiency in LDL removal both of membrane filtration as of dextrane sulphate adsorption on 14 FH patients, performing 302 procedures. Cholesterol extraction with the different methods was in the range of 40-65%. Mean cholesterol level was reduced from 7% to 64% depending on the protocol used. The procedures were all performed on an outpatient basis. Side effects occurred rarely and were always of not serious degree. The short and the middle term clinical effects of LDL-Apheresis are then evaluated.


Comparison of the inactivation of mammalian and bacterial O6-alkylguanine-DNA alkyltransferases by O6-benzylguanine and O6-methylguanine.
The inactivation of human and Escherichia coli O6-alkylguanine-DNA alkyltransferase by O6-methylguanine and O6-benzylguanine was compared. When HT29 cell extracts or E. coli Ada protein were incubated in the presence of 200 microM O6-methylguanine for 1 h, alkyltransferase activity was reduced to 44 and 39% of control levels respectively. However, under the same conditions O6-benzylguanine completely depleted alkyltransferase activity in the extract from human cells but had virtually no effect on the Ada protein. Incubation of the HT29 cell alkyltransferase with O6-benzyl[3H]guanine resulted in a time-dependent production of [3H]guanine. No similar production of [3H]guanine was observed in the presence of the Ada protein. In CHO cells transfected with the bacterial ada gene (CHO-ada) or the human alkyltransferase cDNA (CHO-MGMT), treatment with 500 microM O6-methylguanine inhibited both alkyltransferases by greater than 85%. In contrast, 2 microM O6-benzylguanine inhibited human alkyltransferase expressed in CHO-MGMT cells by greater than 99% though concentrations as high as 25 microM for 24 h had no inhibitory effects on the bacterial alkyltransferase expressed in CHO-ada cells. This selective inhibition was also observed in vivo in transgenic mice expressing ada in the liver where O6-benzylguanine caused a decrease of only 40% in total hepatic alkyltransferase activity compared to 95% in non-transgenic mice, consistent with inhibition of only the mammalian alkyltransferase and maintenance of bacterial alkyltransferase activity in these animals. Thus, while O6-methylguanine at high concentrations inactivates both bacterial and mammalian alkyltransferases, O6-benzylguanine is a substrate only for the mammalian protein and is unable, perhaps due to steric hindrance, to inhibit the Ada protein.


Influenza A H5N1 and H7N9 in China: A spatial risk analysis.
Zoonotic avian influenza poses a major risk to China, and other parts of the world. H5N1 has remained endemic in China and globally for nearly two decades, and in 2013, a novel zoonotic influenza A subtype H7N9 emerged in China. This study aimed to improve upon our current understanding of the spreading mechanisms of H7N9 and H5N1 by generating spatial risk profiles for each of the two virus subtypes across mainland China. In this study, we (i) developed a refined data set of H5N1 and H7N9 locations with consideration of animal/animal environment case data, as well as spatial accuracy and precision; (ii) used this data set along with environmental variables to build species distribution models (SDMs) for each virus subtype in high resolution spatial units of 1km2 cells using Maxent; (iii) developed a risk modelling framework which integrated the results from the SDMs with human and chicken population variables, which was done to quantify the risk of zoonotic transmission; and (iv) identified areas at high risk of H5N1 and H7N9 transmission. We produced high performing SDMs (6 of 8 models with AUC > 0.9) for both H5N1 and H7N9. In all our SDMs, H7N9 consistently showed higher AUC results compared to H5N1, suggesting H7N9 suitability could be better explained by environmental variables. For both subtypes, high risk areas were primarily located in south-eastern China, with H5N1 distributions found to be more diffuse and extending more inland compared to H7N9. We provide projections of our risk models to public health policy makers so that specific high risk areas can be targeted for control measures. We recommend comparing H5N1 and H7N9 prevalence rates and survivability in the natural environment to better understand the role of animal and environmental transmission in human infections.


Effect of different doses of Malaysian honey on reproductive parameters in adult male rats.
The aim of this study was to evaluate the effect of different doses of Malaysian honey on male reproductive parameters in adult rats. Thirty-two healthy adult male Sprague-Dawley rats were randomly divided into four groups (eight rats per group). Group 1 (control group) was given 0.5 ml of distilled water. Groups 2, 3 and 4 were given 0.2, 1.2 and 2.4 g kg(-1) body weight of honey respectively. The rats were treated orally by gavage once daily for 4 weeks. Honey did not significantly alter body and male reproductive organs weights. The rats in Group 3 which received honey at 1.2 g kg(-1) had significantly higher epididymal sperm count than those in Groups 1, 2 and 4. No significant differences were found for the percentage of abnormal sperm, elongated spermatid count, reproductive hormonal levels as well as the histology of the testis among the groups. In conclusion, Malaysian honey at a dose of 1.2 g kg(-1) daily significantly increased epididymal sperm count without affecting spermatid count and reproductive hormones. These findings might suggest that oral administration of honey at this dose for 4 weeks may enhance spermiogenesis in adult rats.


Photoperiodic response of the hypothalamo-pituitary-gonad axis in male and female canaries, Serinus canaria.
Although the gonadal photoperiodic response and its influence upon the song control system in canaries have been extensively studied, photoperiodic regulation of the GnRH system has not been investigated. To examine the relationship between photoperiod and the reproductive neuroendocrine system in male and female canaries, three groups of canaries were exposed to chronic short days (8L:16D; Phsens), acute long days (18L:6D; Phstim) and chronic long days (also 18L:6D; Phrefr) to induce the reproductive states of photosensitivity, photostimulation, and photorefractoriness, respectively. Brain sections were processed for GnRH immunocytochemistry. The canaries in this study did not demonstrate consistent or uniform responses to different photoperiodic treatments. In males, gonad size varied with photoperiod; Phstim males had larger gonads than either the Phsens or Phrefr males. In contrast, there was no difference between groups in female gonad size as a result of photoperiodic treatment. Brain GnRH cell number, cell size, and fiber density were similar in all groups. The results suggest that canaries are not as obligatory photoperiodic as previously thought (or at least not all varieties of domestic canaries are). This could be a result of many years of domestication, the natural history of the species, phylogenetic constraint, or a combination of these factors.


Wavefront distortion of the reflected and diffracted beams produced by the thermoelastic deformation of a diffraction grating heated by a Gaussian laser beam.
It may be advantageous in advanced gravitational-wave detectors to replace conventional beam splitters and Fabry-Perot input mirrors with diffractive elements. In each of these applications, the wavefront distortions produced by the absorption and subsequent heating of the grating can limit the maximum useful optical power. We present data on the wavefront distortions induced in a laser probe beam for both the reflected and diffracted beams from a grating that is heated by a Gaussian laser beam and compare these results to a simple theory of the wavefront distortions induced by thermoelastic deformations.


Vaccines for malaria: how close are we?
Vaccines are the most powerful public health tools mankind has created, but malaria parasites are bigger, more complicated, and wilier than the viruses and bacteria that have been conquered or controlled with vaccines. Despite decades of research toward a vaccine for malaria, this goal has remained elusive. Nevertheless, recent advances justify optimism that a licensed malaria vaccine is within reach. A subunit recombinant protein vaccine that affords in the neighborhood of 50% protective efficacy against clinical malaria is in the late stages of clinical evaluation in Africa. Incremental improvements on this successful vaccine are possible and worth pursuing, but the best hope for a highly efficacious malaria vaccine that would improve prospects for malaria eradication may lie with the use of attenuated whole parasites and powerful immune-boosting adjuvants.


Developmental regression in children: Current and future directions.
Developmental regression describes when a child loses previously established skills, such as the ability to speak words and is most recognised in neurodevelopmental conditions including Autism; Developmental Epileptic Encephalopathies, such as Landau Kleffner syndrome, and genetic conditions such as Rett syndrome and Phelan McDermid syndrome. Although studies have reported developmental regression for over 100 years, there remain significant knowledge gaps within and between conditions that feature developmental regression. The certainty of evidence from earlier work has been limited by condition-specific studies, retrospective methodology, and inconsistency in the definitions and measures used for classification. Given prior limitations in the field, there is a paucity of knowledge about neurocognitive mechanisms, trajectories and outcomes for children with developmental regression, and their families. Here we provide a comprehensive overview, synthesise key definitions, clinical measures, and aetiological clues associated with developmental regression and discuss impacts on caregiver physical and mental health to clarify challenges and highlight future directions in the field.


Performance of serological and molecular tests within acute HIV infection.
Early diagnosis of acute HIV infection can be challenging and is critical in regards to early therapeutic decision making. To evaluate the performance of different HIV tests in detecting early infections. A total of 83 leftover specimens of 61 study participants who seroconverted were used in this sub-study. 35 HIV RNA positive but still seronegative specimens (acute infections) were used for analysis of the sensitivity of the different assays in detecting early infections and 42 HIV RNA and antibody negative specimens were used for specificity analysis. Four (11%) specimens out of 35 acute infections were reactive with the Enzygnost® Anti-HIV 1/2 Plus and 12/35 (34%) with the Vironostika® HIV Ag/Ab. 16 (46%) specimens were confirmed as acute by the INNOTEST® HIV antigen mAb Antigen test. Only three (9%), 10 (29%) and 9 (27%) specimens were reactive with the Determine HIV-1/2 Ag/Ab Combo, SD Bioline HIV Ag/Ab Combo test and the HIV Combo test, respectively. The specificity of the different tests were 100%, 95%, 100%, 93%, 100% and 93% for Enzygnost® Anti-HIV 1/2 Plus, Vironostika® HIV Ag/Ab, INNO-Test HIV antigen mAb, Determine HIV-1/2 Ag/Ab Combo, SD Bioline HIV Ag/Ab Combo test and HIV Combo test respectively. RNA test, 4th generation ELISA and Single Ag test are the most sensitive tests for detection of an acute infection. As an alternative, the HIV Combo test is generally slightly more sensitive compared to its previous version, but the SD Bioline HIV Ag/Ab Combo tests has the best performance compared to the other simple rapid tests (SRTs) but none of them are precise in detecting Ag in the determination of acute infections.


The septic multiple-trauma patient.
Sepsis in the multiple trauma patient is being seen with increased frequency now that more of these patients are surviving the initial period. Traumatic destruction of tissue barriers, the placement of various tubes and drains, and surgical repair with debridement all provide conduits for colonization and infection with pathogens. Many components of the host immune system also become altered after trauma and surgery, predisposing this population to infectious complications. The site of infection can be cryptic in the moribund trauma patient; locating it may require many special diagnostic procedures. Continuing close surveillance is important to prevent or to identify infections at the earliest possible time. The liberal use of antibiotics should be discouraged so that development of resistant organisms and superinfection is kept to a minimum. Handwashing between patient contacts may be the most important prophylaxis against the spread of pathogens within a trauma unit.


Leptin receptor+ cells promote bone marrow innervation and regeneration by synthesizing nerve growth factor.
The bone marrow contains peripheral nerves that promote haematopoietic regeneration after irradiation or chemotherapy (myeloablation), but little is known about how this is regulated. Here we found that nerve growth factor (NGF) produced by leptin receptor-expressing (LepR+) stromal cells is required to maintain nerve fibres in adult bone marrow. In nerveless bone marrow, steady-state haematopoiesis was normal but haematopoietic and vascular regeneration were impaired after myeloablation. LepR+ cells, and the adipocytes they gave rise to, increased NGF production after myeloablation, promoting nerve sprouting in the bone marrow and haematopoietic and vascular regeneration. Nerves promoted regeneration by activating β2 and β3 adrenergic receptor signalling in LepR+ cells, and potentially in adipocytes, increasing their production of multiple haematopoietic and vascular regeneration growth factors. Peripheral nerves and LepR+ cells thus promote bone marrow regeneration through a reciprocal relationship in which LepR+ cells sustain nerves by synthesizing NGF and nerves increase regeneration by promoting the production of growth factors by LepR+ cells.


A novel antidiuretic hormone governs tumour-induced renal dysfunction.
Maintenance of renal function and fluid transport are essential for vertebrates and invertebrates to adapt to physiological and pathological challenges. Human patients with malignant tumours frequently develop detrimental renal dysfunction and oliguria, and previous studies suggest the involvement of chemotherapeutic toxicity and tumour-associated inflammation1,2. However, how tumours might directly modulate renal functions remains largely unclear. Here, using conserved tumour models in Drosophila melanogaster3, we characterized isoform F of ion transport peptide (ITPF) as a fly antidiuretic hormone that is secreted by a subset of yki3SA gut tumour cells, impairs renal function and causes severe abdomen bloating and fluid accumulation. Mechanistically, tumour-derived ITPF targets the G-protein-coupled receptor TkR99D in stellate cells of Malpighian tubules-an excretory organ that is equivalent to renal tubules4-to activate nitric oxide synthase-cGMP signalling and inhibit fluid excretion. We further uncovered antidiuretic functions of mammalian neurokinin 3 receptor (NK3R), the homologue of fly TkR99D, as pharmaceutical blockade of NK3R efficiently alleviates renal tubular dysfunction in mice bearing different malignant tumours. Together, our results demonstrate a novel antidiuretic pathway mediating tumour-renal crosstalk across species and offer therapeutic opportunities for the treatment of cancer-associated renal dysfunction.


In vitro pulsatile flow velocity and turbulent shear stress measurements in the vicinity of mechanical aortic heart valve prostheses.
A two-dimensional laser Doppler anemometer system was used to study the velocity and turbulent shear stress fields created by various types of mechanical aortic heart valve prostheses under physiological pulsatile flow conditions. The prosthetic valves studied were the Starr-Edwards caged ball valve, Bjork-Shiley tilting disc valve, Medtronic-Hall tilting disc valve, and St. Jude bileaflet valve. The results indicate that all four prosthetic valve designs studied create very disturbed flow fields with regions of flow separation and/or stagnation and regions of elevated turbulent shear stress. The maximum values of the mean turbulent shear stresses measured during peak systole were 1200 dynes/cm2 for the Starr-Edwards valve, 1600 dynes/cm2 for the Bjork-Shiley valve, 1000 dynes/cm2 for the Medtronic-Hall valve, and 1050 dynes/cm2 for the St. Jude valve. The corresponding values during the deceleration phase were about 800, 600, 450 and 800 dynes/cm2, respectively. These elevated turbulent shear stresses could cause sublethal and/or lethal damage to blood elements, and, together with the regions of flow separation and/or stagnation, could lead to thrombus formation and/or tissue overgrowth on the valve structure, as observed on the clinically recovered prosthetic valves.