Preparation and application of a restricted access material with hybrid poly(glycerol mono-methacrylate) and cross-linked bovine serum albumin as hydrophilic out layers for directly on-line high performance liquid chromatography analysis of enrofloxacin and gatifloxacin in milk samples.
A novel restricted access material (RAM) was prepared through combination of hydrophilic polymer poly(glycerol mono-methacrylate) and cross-linking bovine serum albumin (BSA) for direct biological analysis. In the material preparation, the poly(styrene-co-divinylbenzene) and poly(glycerol mono-methacrylate) were grafted on silica successively by atom transfer radical polymerization. Then the BSA was adsorbed on the material and cross-linked through an in-column process. The BSA recoveries of the resulted RAM were higher than 99.3%. Small molecules such as alkylbenzene and quinolone antibiotics could be retained with a reversed phase mechanism. The column packed with RAM had good long term stability and could last at least five months without significantly changed in its efficiencies. An on-line SPE/HPLC method for the analysis of enrofloxacin and gatifloxacin in milk samples was established by using the resulted RAM as the solid-phase extraction material. The detection and quantitation limits of two antibiotics were 8.22 and 27.4 ng mL-1, respectively. In the method validation, least recovery 88.5% with relative standard deviation of less than 3.9% was obtained. It demonstrated that the method is reliable and the material can be used for the direct analysis of veterinary drug residues in biological samples.


Dramatic post-cardiotomy outcome, due to severe anaphylactic reaction to protamine.
Immunologic reactions to protamine sulfate during cardiac surgery are very rare. The frequency and outcome of such adverse reactions is unclear. We report a case of lethal anaphylactic reaction to protamine that occurred in a non-diabetic patient following the uneventful replacement of the ascending aorta. We also briefly review the mechanisms of this adverse reaction and emit some considerations on the management of this situation.


Attention to central and peripheral visual space in a movement detection task. III. Separate effects of auditory deprivation and acquisition of a visual language.
We employed event-related brain potentials (ERPs) and measures of signal detectability to compare attention to peripheral and central visual stimuli in normal hearing subjects who were born to deaf parents (HD Ss) and whose first language was American Sign Language (ASL). The results were compared with those obtained from normal hearing Ss and congenitally deaf Ss in the same paradigm. Task performance and ERPs during attention to the foveal region were similar in the 3 groups. In contrast, with attention to the peripheral stimuli the deaf Ss displayed attention effects over the occipital regions of both hemispheres that were several times larger than those in the hearing and the HD Ss. However, both HD and deaf Ss displayed lateral asymmetries in behavior and ERPs that were opposite in direction to those of the hearing Ss. Whereas hearing Ss detected the direction of target motion better when it occurred in the left visual field, deaf and HD Ss performed better for right visual field targets. Consistent with these results, the amplitude of the attention-related increases in the ERPs were larger from temporal and parietal regions of the right than the left hemisphere in hearing Ss, but were larger from the left than the right hemisphere in both the HD and the deaf Ss. These results suggest that auditory deprivation and the acquisition of a visual language have marked and different effects on the development of cortical specializations in humans.


Relationship between urine beta-2-microglobulin and platinum levels during cisplatin treatment.
We evaluated whether urine beta 2-microglobulin (beta 2M) excretion as a function of nephrotoxicity correlated with plasma and urine platinum levels in patients receiving cisplatin. Thirty-one patients had urine platinum measurements in urine samples collected at 0 to 6 and 6 to 24 h after cisplatin administration, 25 of these patients had serial plasma platinum measurements. Sixteen of the 31 patients had an increase in urine beta 2M. A significant correlation was obtained between urine platinum and beta 2M in the 6- to 24-h samples (r = 0.61, p less than 0.02). The mean plasma platinum levels were higher (12.6 +/- 6.1 mumol/L) in the patients with an increase in urine beta 2M compared to those patients with no change in beta 2M (6.8 +/- 4.1 mumol/L) (p less than 0.02). Our study indicates that tubular damage occurs within 24 h after cisplatin administration and that the damage correlates with urine platinum levels.


Comprehensive chlorophyll composition in the main edible seaweeds.
Natural chlorophylls present in seaweeds have been studied regarding their biological activities and health benefit effects. However, detailed studies regarding characterization of the complete chlorophyll profile either qualitatively and quantitatively are scarce. This work deals with the comprehensive spectrometric study of the chlorophyll derivatives present in the five main coloured edible seaweeds. The novel complete MS2 characterization of five chlorophyll derivatives: chlorophyll c2, chlorophyll c1, purpurin-18 a, pheophytin d and phytyl-purpurin-18 a has allowed to obtain fragmentation patterns associated with their different structural features. New chlorophyll derivatives have been identified and quantified by first time in red, green and brown seaweeds, including some oxidative structures. Quantitative data of the chlorophyll content comes to achieve significant information for food composition databases in bioactive compounds.


Genetic polymorphisms of MDM2, cumulative cigarette smoking and nonsmall cell lung cancer risk.
Abnormalities of the tumor suppressor TP53 pathway are critical in the development of many cancers since it regulates cell cycle components and apoptosis. Murine double minute-2 (MDM2) protein is a central node in the p53 pathway and a direct negative regulator of p53. The MDM2 SNP309 (rs2279744) polymorphism increases MDM2 RNA and protein levels, attenuating the p53 pathway. The MDM2 SNP309 polymorphism was investigated in 1,787 Caucasian nonsmall cell lung cancer (NSCLC) patients and 1,360 healthy controls. Cases and controls were analyzed for associations with genotype and adjusted for age, gender, histology and smoking history. There were no overall associations between the MDM2 genotypes and risk of lung cancer (adjusted odds ratios [AORs] = 0.82 [95% confidence interval [CI] = 0.6-1.1] for the T/G genotype and AOR = 1.32 [95% CI = 0.9-2.0] for the G/G genotype). A statistically significant interaction (p = 0.01) was found between smoking and MDM2 genotypes. Consistent with this interaction, stratified analysis by pack-years of smoking demonstrated that the AORs of G/G vs. T/T were 1.56 (1.0-2.7), 1.46 (1.0-2.2), 0.80 (0.5-1.3) and 0.63 (0.4-1.1), respectively, for never, mild (<30 pack-years), moderate (30-57 pack-years) and heavy smokers (>or=58 pack-years). In conclusion, a strong gene-smoking interaction was observed between the MDM2 SNP309 and NSCLC risk.


CO2-Assisted Sugar Cane Gasification Using Transition Metal Catalysis: An Impact of Metal Loading on the Catalytic Behavior.
To meet the increasing needs of fuels, especially non-fossil fuels, the production of "bio-oil" is proposed and many efforts have been undertaken to find effective ways to transform bio-wastes into valuable substances to obtain the fuels and simultaneously reduce carbon wastes, including CO2. This work is devoted to the gasification of sugar cane bagasse to produce CO in the process assisted by CO2. The metals were varied (Fe, Co, or Ni), along with their amounts, in order to find the optimal catalyst composition. The materials were investigated by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), X-ray diffraction (XRD), and electron diffraction, and were tested in the process of CO2-assisted gasification. The catalysts based on Co and Ni demonstrate the best activity among the investigated systems: the conversion of CO2 reached 88% at ~800 °C (vs. 20% for the pure sugarcane bagasse). These samples contain metallic Co or Ni, while Fe is in oxide form.


In Vivo Detection of Retinal Ganglion Cell Stress in Rodents with DARC.
DARC (detection of apoptosing retinal cells) uses fluorescently tagged Annexin A5 to identify retinal apoptosis non-invasively in vivo using a confocal laser scanning ophthalmoscope (cSLO). This can provide insights into the presence and progression of disease pathology and the efficacy of neuroprotective intervention. The methods of administration, imaging, and quantification of DARC, including the operation of the cSLO, are described here.


Nurses' perspectives of violence in emergency departments: A metasynthesis.
Workplace violence against nurses in the Emergency Department (ED) is a significant issue worldwide and has received increased attention. Workplace violence against nurses in the ED has increased in recent years. With such a large number of nurses having experienced violence, it is important to understand and elucidate the nurses' perspective of violence in the ED. Qualitative studies that were published between 2010 and 2019. A metasynthesis of 6 qualitative studies was conducted using Noblit and Hare's metaethnographic methodology. The Critical Appraisal Skills Program (CASP) was used to evaluate the quality of the studies. Four overarching themes emerged from the data: the inevitability of violence, invisible wounds and painful memories, post-violence repercussions, and double-sided: physical and verbal abuse. Findings provide insight into policies actions related to perpetrators and developing violence protections guidelines to support ED nurses in managing workplace violence. Violence in the ED is an inevitable experience for nurses. Organizations must take a realistic approach to implement violence reduction measures and training programs in the ED.


Biological effects of insulin on murine melanoma cells and fish erythrophoroma cells: a comparative study.
Insulin is the hormone that plays an essential role in metabolism and mitosis of normal and tumor cells, exerting its pleiotropic effects through binding to specific membrane receptors and promoting the phosphorylation of tyrosine residues of the receptor itself and of other components of the signaling pathway. The aim of this study was to investigate the effects of insulin on melanogenesis and cell growth in three different cell lines: the goldfish GEM-81 erythrophoroma cells (undifferentiated and differentiated with 1.5% dimethylsulfoxide-DMSO), and the murine B16F10 and Cloudman S91 melanoma cells. Undifferentiated GEM-81 and B16F10 cells responded to insulin with a small increase of cell proliferation, whereas S91 cells responded with a decrease of growth. In the two mammalian cell lines, and in DMSO-differentiated GEM-81 cells, the hormone strongly inhibited melanogenesis, by decreasing tyrosinase activity. In undifferentiated GEM-81 cells, insulin had no effect on tyrosinase activity. An increase in the tyrosine phosphorylation status of pp185 (insulin receptor substrate 1 and 2 -- IRS-1/2) phosphorylation degree was observed in S91 mouse melanoma and in differentiated GEM-81 erythrophoroma cells, suggesting that this specific protein was maintained during transformation process and participates in insulin signaling. Our results imply an ancient and diverse history of the insulin signaling system in vertebrate pigment cells.


Nucleoli and Promyelocytic Leukemia Protein (PML) bodies are phase separated nuclear protein quality control compartments for misfolded proteins.
We uncovered a role for nucleoli and PML-bodies as phase-separated protein quality control organelles that compartmentalize protein quality control factors and misfolded proteins for their efficient clearance. Failure to dispose misfolded proteins converts nucleoli and PML-bodies into a solid state that immobilizes ubiquitin, limiting its recycling for genome integrity maintenance.


Determination of elastase activity by reversed-phase high-performance liquid chromatography.
The action of elastase on elastin was measured by high-performance liquid chromatography with on-line post-column derivatization. After alkaline hydrolysis, a 20-ml sample was injected into a ODS-2 gel column. An elastin-specific dipeptide, Val-Pro, and the internal standard, Gly-Leu, were eluted by a linear gradient of 0 to 10% of 1-propanol in 50 mM heptafluorobutyrate (pH 3) at a flow-rate of 1 ml/min. The eluent was reacted with fluorescamine, and the fluorescent products were measured. Retention times for Val-Pro and Gly-Leu were 17.33 and 23.54 min. The peak areas of 0.2-16 micrograms of Val-Pro gave a straight-line plot. Elastase activity was constant from 6 to 24 h and was 0.95 +/- 0.02 (S.D.) micrograms/h. The method may be useful for the measurement of the elastolytic activity in some diseased tissues.


Isolation and structural analysis of two lipid A precursors from a KDO deficient mutant of Salmonella typhimurium differing in their hexadecanoic acid content.
The extraction, purification and structural characterization of two lipid A precursors (Ia and Ib) differing only in one hexadecanoic acid are described. Both precursors were synthesized at elevated temperatures by a new mutant of Salmonella typhimurium (mutant Ts5) which is conditionally defective in synthesis of the 3-deoxy-D-manno-octulosonic acid region of lipopolysaccharides. Both precursors were purified by repeated phenol/chloroform/petroleum ether (PCP) extractions followed by thin layer chromatography. The precursor preparation was free of lipopolysaccharides and phospholipids and contained less than 0.1% protein. Structural analysis which included chemical degradation procedures as well as positive ion laser desorption (LDMS) mass spectroscopy of dephosphorylated lipid A precursors showed together that precursor Ia represents a diphosphorylated glucosamine disaccharide containing two ester, two amide-linked residues of 3-hydroxytetradecanoic acid and lacks the ester-linked dodecanoic, tetradecanoic and hexadecanoic acid as well as 3-deoxy-D-manno-octulosonic acid. Precursor Ib has the same basic structure as precursor Ia, but contains in addition one mol of hexadecanoic acid per mol disaccharide which is linked to the 3-hydroxy group of the amide-bound 3-hydroxy-tetradecanoic acid of the reducing, terminal glucosamine residue. The structure of precursor Ib supports the conclusion that hexadecanoic acid incorporation occurs at an early stage in lipid A biosynthesis prior to the attachment of 3-deoxy-D-manno-octulosonic acid and/or other polar substituents.


Grade IV Renal Laceration in a 13-Year-Old Boy With Cross-fused Renal Ectopia.
A 13-year-old boy presented with gross hematuria following a skateboarding accident and was found to have cross-fused renal ectopia of the left kidney with a grade IV right renal laceration and urinary extravasation. Despite a double-J ureteral stent, urinoma drain, and indwelling bladder catheter, his urinoma drain maintained high output. He underwent a ureteral stent exchange and upsizing. A percutaneous nephrostomy tube was subsequently placed for maximal urinary diversion, which ultimately led to the resolution in his urinary leak. This case highlights our endourologic approach to manage a severe urinary leak despite conservative measures in a pediatric patient with a renal anomaly.


Loss of hair cells and threshold sensitivity during prolonged noise exposure in normotensive albino rats.
The relation between hearing loss and loss of hair cells after prolonged exposure to a simulated industrial noise environment was determined in normotensive albino rats. Hearing loss was assessed behaviorally by a conditioned suppression technique and electrophysiologically by auditory brainstem response to pulses of 1/3 octave filtered full cycle sine waves. The ears were analyzed in surface preparations and the hair cells counted. Sixty-two ears from 46 animals were analyzed after 1, 3, 7, and 15 months of exposure. A hearing loss of up to approximately 30 dB was consistently found with minimal loss of hair cells. Between 30 and 60 dB hearing loss there was a fair correspondence between loss of function and loss of hair cells. After 15 months exposure a relatively larger loss of hair cells was observed than expected from decrease of threshold sensitivity. The results indicate the existence of a systematic although not directly proportional relation between hair cell loss and loss of sensitivity during prolonged noise exposure. It is suggested that the correlation between hearing loss and hair cell loss is influenced, e.g., by duration and level of exposure, degree of hearing loss, and location along the basilar membrane.


Postoperative three-dimensional cervical range of motion and neurological outcomes in patients with cervical ossification of the posterior longitudinal ligament: Cervical laminoplasty versus laminectomy with fusion.
Laminoplasty (LP) and laminectomy with fusion (LCF) are acceptable surgical options for cervical myelopathy caused by ossification of the posterior longitudinal ligament (OPLL). This study focused on evaluating cervical range of motion (ROM) on a three-dimensional basis as well as neurological outcomes after LP and LCF. This prospective cohort study consisted of 38 patients undergoing LP (n=20) or LCF (n=18) from December 2010 to December 2012. Before surgery and at the 3rd, 6th, 12th month follow-up, patients were assessed with three-dimensional cervical ROM, Japanese Orthopaedic Association (JOA) scores, Visual Analogue Scale (VAS) and complications. The patients in both groups had significant ROM loss after surgery in six directions of motion. At the 12th month follow-up, the LP group preserved more ROM than LCF in all directions except bilateral rotations. Major reduction was observed in extension, as with only 59.8% and 54.3% ROM preserved in LP and LCF groups. However, the most preserved ROM was witnessed in rotation, especially in the LP group (90.8%). For JOA and VAS, both groups showed significant improvements postoperatively, and the difference between the two groups was not statistically significant. Patients with OPLL had an obvious reduction in active cervical ROM following LP and LCF. Major reduction was observed in extension, and less impact was detected on rotation. Compared with LCF, LP had better ROM preserved. Both LP and LCF provided patients with significant neurological improvement.


HAT Catalysts to Facilitate Acid Mediated Cleavage of Biaryl C-C Bonds in Binaphthols.
A method to cleave the C-C biaryl bond of binaphthyl derivatives under reductive conditions is described. Triflic acid employed together with a catalytic HAT reagent, 2-ethyl-9,10-dihydroxyanthracene, that is regenerated using H2 with catalytic Pd/C yielded monomeric products in improved yields. A range of substrates is disclosed, and kinetic analyses provide insight into the mechanism of aryl-aryl activation.


Processing of cDNA and genomic kilobase-size clones for massive screening, mapping and sequencing by hybridization.
Efficient procedures for managing a large number of M13 or plasmid clones have been developed. In addition to picking, clones are directly arrayed in multiwell plates by dispensing diluted transformation mixtures. Metal pin arrays are used for fast inoculations of preparative plates filled by medium or by PCR mixture. Growth of M13 clones in multiwell plates is optimized to obtain a consistently high yield, and a PCR protocol is defined for reliable amplification of several thousand M13 or plasmid inserts per day in BioOvens. Over 80,000 cDNA inserts have been amplified. The phages or amplified inserts are spotted on nylon filters using an array of pins having a flat bottom, 0.3 mm in diameter. The procedures are suitable for an automated processing of hundreds of thousands of short clones from representative cDNA and genomic libraries. Hybridization of arrayed clones with oligonucleotide and complex probes can simplify the search for new genes and accelerate large-scale sequencing.


Geographic differentiation of polymorphism in the Plasmodium falciparum malaria vaccine candidate gene SERA5.
SERA5 is regarded as a promising malaria vaccine candidate of the most virulent human malaria parasite Plasmodium falciparum. SERA5 is a 120 kDa abundantly expressed blood-stage protein containing a papain-like protease. Since substantial polymorphism in blood-stage vaccine candidates may potentially limit their efficacy, it is imperative to fully investigate polymorphism of the SERA5 gene (sera5). In this study, we performed evolutionary and population genetic analysis of sera5. The level of inter-species divergence (kS=0.076) between P. falciparum and Plasmodium reichenowi, a closely related chimpanzee malaria parasite is comparable to that of housekeeping protein genes. A signature of purifying selection was detected in the proenzyme and enzyme domains. Analysis of 445 near full-length P. falciparum sera5 sequences from nine countries in Africa, Southeast Asia, Oceania and South America revealed extensive variations in the number of octamer repeat (OR) and serine repeat (SR) regions as well as substantial level of single nucleotide polymorphism (SNP) in non-repeat regions (2562 bp). Remarkably, a 14 amino acid sequence of SERA5 (amino acids 59-72) that is known to be the in vitro target of parasite growth inhibitory antibodies was found to be perfectly conserved in all 445 worldwide isolates of P. falciparum evaluated. Unlike other major vaccine target antigen genes such as merozoite surface protein-1, apical membrane antigen-1 or circumsporozoite protein, no strong evidence for positive selection was detected for SNPs in the non-repeat regions of sera5. A biased geographical distribution was observed in SNPs as well as in the haplotypes of the sera5 OR and SR regions. In Africa, OR- and SR-haplotypes with low frequency (<5%) and SNPs with minor allele frequency (<5%) were abundant and were mostly continent-specific. Consistently, significant genetic differentiation, assessed by the Wright's fixation index (Fst) of inter-population variance in allele frequencies, was detected for SNPs and both OR- and SR-haplotypes among almost all parasite populations. The exception was parasite populations between Tanzania and Ghana, suggesting frequent gene flow in Africa. The present study points to the importance of investigating whether biased geographical distribution for SNPs and repeat variants in the OR and SR regions affect the reactivity of human serum antibodies to variants.


Platelet-Derived S100A8/A9 and Cardiovascular Disease in Systemic Lupus Erythematosus.
Levels of S100A8/A9, a proinflammatory and prothrombotic protein complex, are increased in several diseases, and high levels predispose to cardiovascular disease (CVD). Recently, platelet S100A8/A9 synthesis was described in mice and humans in relation to CVD. The aim of this study was to investigate the role of platelet S100A8/A9 in systemic lupus erythematosus (SLE), a disease with markedly increased cardiovascular morbidity, as well as the exact platelet distribution of the S100A8/A9 proteins. The occurrence and distribution of platelet S100A8/A9 protein were detected by enzyme-linked immunosorbent assay, electron microscopy, Western blotting, and flow cytometry in healthy controls (n = 79) and in 2 individual cohorts of SLE patients (n = 148 and n = 318, respectively) and related to cardiovascular morbidity. We observed that human platelets expressed S100A8/A9 proteins, and that these were localized in close proximity to intracellular membranes and granules as well as on the cell surface upon activation with physiologic and pathophysiologic stimuli. Interestingly, S100A8/A9 was enriched at sites of membrane interactions, indicating a role of S100A8/A9 in cell-cell communication. S100A8/A9 levels were highly regulated by interferon-α, both in vivo and in vitro. Patients with SLE had increased platelet S100A8/A9 content compared with healthy individuals. Increased levels of platelet S100A8/A9 were associated with CVD, particularly myocardial infarction (odds ratio 4.8, 95% confidence interval 1.5-14.9, P = 0.032 [adjusted for age, sex, and smoking]). Platelets contain S100A8/A9 in membrane-enclosed vesicles, enabling rapid cell surface deposition upon activation. Furthermore, platelet S100A8/A9 protein levels were increased in SLE patients, particularly in those with CVD, and may be a future therapeutic target.


A hybrid feature extraction scheme for efficient malonylation site prediction.
Lysine malonylation is one of the most important post-translational modifications (PTMs). It affects the functionality of cells. Malonylation site prediction in proteins can unfold the mechanisms of cellular functionalities. Experimental methods are one of the due prediction approaches. But they are typically costly and time-consuming to implement. Recently, methods based on machine-learning solutions have been proposed to tackle this problem. Such practices have been shown to reduce costs and time complexities and increase accuracy. However, these approaches also have specific shortcomings, including inappropriate feature extraction out of protein sequences, high-dimensional features, and inefficient underlying classifiers. A machine learning-based method is proposed in this paper to cope with these problems. In the proposed approach, seven different features are extracted. Then, the extracted features are combined, ranked based on the Fisher's score (F-score), and the most efficient ones are selected. Afterward, malonylation sites are predicted using various classifiers. Simulation results show that the proposed method has acceptable performance compared with some state-of-the-art approaches. In addition, the XGBOOST classifier, founded on extracted features such as TFCRF, has a higher prediction rate than the other methods. The codes are publicly available at: https://github.com/jimy2020/Malonylation-site-prediction.


A comparison of bronchial blocker under artificial pneumothorax and double-lumen endobronchial tube for lung isolation in thoracoscopic enucleation of oesophageal leiomyoma.
Oesophageal leiomyomas are one of the most common benign oesophageal tumours. This retrospective, observational study summarized and compared the clinical outcomes of thoracoscopic enucleation of oesophageal leiomyoma between single-lumen endotracheal intubation with a bronchial blocker and double-lumen endotracheal intubation. A total of 36 patients who underwent thoracoscopic enucleation of oesophageal leiomyoma at Peking Union Medical College Hospital between 2014 and 2020 were retrospectively analysed. Fifteen patients received single-lumen endotracheal intubation combined with a right bronchial blocker (SLT-B group), and twenty-one patients received double-lumen endotracheal intubation (DLT group). Clinical data, surgical variables, and postoperative complications were analysed and compared. The average tumour size in all patients was 4.3 ± 2.0 cm. The average tumour size among symptomatic patients was significantly larger than that among asymptomatic patients (5.1 ± 2.0 cm vs 3.7 ± 1.7 cm, P < 0.05). Patients in the SLT-B group had a significantly larger average tumour size than patients in the DLT group (5.4 ± 2.1 cm vs 3.5 ± 1.4 cm, P < 0.05). The SLT-B group had a significantly shorter operation time and shorter total hospital stay than the DLT group. No mucosal injury, conversion to thoracotomy, or other operative complications occurred in the SLT-B group. In the follow-up, no recurrence, dysphagia, or regurgitation was found in any of the patients. Compared with traditional double-lumen intubation, artificial pneumothorax-assisted single-lumen endotracheal intubation combined with a bronchial blocker for thoracoscopic oesophageal leiomyoma enucleation can achieve complete removal of larger tumours, with fewer complications and shorter hospital stays.


Hepatitis B vaccination in healthy Chinese adults with low dose regimens.
Three hundred seronegative healthy Chinese adults were divided randomly into three groups to receive 5, 2 and 1 micrograms of Pasteur's hepatitis B vaccine on a four dose schedule. No difference between the three groups was observed in the antibody to hepatitis B surface antigen (anti-HBs) response rate (96, 92 and 94%, respectively) a month following the fourth dose of vaccination. Young vaccinees had a faster and higher anti-HBs response than older ones. There was no difference in antibody response rate by sex. This study shows a good immunogenic effect for low dose hepatitis B vaccine in Chinese adults. The use of low dose (1 microgram) hepatitis B vaccine in susceptible adults would make mass hepatitis B vaccination more economically feasible.


Synthesis and antidiabetic performance of β-amino ketone containing nabumetone moiety.
We wish to report the further design and improved synthesis that resulted in two series of target molecules, TM-1 and TM-2, with remarkably simplified structures containing β-amino ketone of discrete nabumetone moiety. These were obtained via a 'one-pot, two-step, three-component' protocol of Mannich reaction with yield up to 97%. A total of 28 out of 31 new compounds were characterized using (1)H NMR, (13)C NMR, ESI MS and HRMS techniques. Studies on their antidiabetic activities, screened in vitro at 10 μg mL(-1) level, indicate that TM-2 possesses peroxisome proliferator-activated receptor activation and α-glucosidase inhibition activity significantly stronger than that of TM-1, and also that of the series B compounds that were previously synthesized by the group. Analysis of the structure-activity relationship points to the sulfanilamide unit as the most probable potent group of β-amino ketone and, on the basis of which, a tangible strategy is presented for the development of new antidiabetic drugs.


Chance of aneurysm in patients suspected of SAH who have a 'negative' CT scan but a 'positive' lumbar puncture.
In patients with sudden severe headache and a negative computed tomography (CT) scan, a lumbar puncture (LP) is performed to rule in or out a subarachnoid haemorrhage (SAH), but this procedure is under debate. In a hospital-based series of 30 patients with sudden headache, a negative CT scan but a positive LP (defined as detection of bilirubin >0.05 at wavelength 458 nm), we studied the chance of harbouring an aneurysm and the clinical outcome. Aneurysms were found in none of both patients who presented within 3 days, in 8 of the 18 (44%) who presented within 4-7 days and in 5 of the 10 (50%) who presented within 8-14 days. Of the 13 patients with an aneurysm, 3 (23%) had poor outcome. In patients who present late after sudden headache, the yield in terms of aneurysms is high in those who have a positive lumbar puncture. In patients with an aneurysm as cause of the positive lumbar puncture, outcome is in the same range as in SAH patients admitted in good clinical condition.


"Post-assay" covalent labeling of phosphorothioate-containing nucleic acids with multiple fluorescent markers.
A simple protocol has been developed which allows the covalent introduction of multiple fluorescent markers into DNA fragments after gel electrophoresis techniques, that is, while the nucleic acid is imbedded in the polyacrylamide gel matrix. "Post-assay" fluorescent labeling in this manner employs DNA fragments containing phosphorothioate diesters, which can be easily incorporated during chemical and enzymatic synthesis procedures, and can be alkylated with the fluorescent marker monobromobimane. Labeling the internucleotidic phosphorus residue in this manner allows the introduction of a fluorescent marker for each nucleotide residue present. Roughly a linear increase in emitted fluorescence, thus detection sensitivity, is observed with an increasing number of bimane markers. With this technique, oligodeoxynucleotides and DNA fragments can be observed in the gel matrix, without sophisticated electronic detection devices in the low femtomolar (10(-15) mol) range.


Exploring the Use of State Medical Cannabis Legislation as a Proxy for Medical Cannabis Use Among Patients Receiving Chemotherapy.
The use of medical cannabis is expanding in the USA. Due to conflicting, low-quality evidence, many oncologists may not feel confident to recommend it to patients. Given the potential for legal and financial risks when conducting clinical trials with medical cannabis, the use of observational data should be explored. Observational data that directly capture medical cannabis use in relation to prescription medications and track the prevalence and patterns of cannabis use is sparse. To gain insights into the role medical cannabis plays in the pharmaceutical landscape, proxies such as cannabis legislation need to be explored. In the context of recommendation-nonadherent antiemetic prescribing among patients experiencing chemotherapy-induced nausea and vomiting, medical cannabis may be a suitable alternative to an antiemetic in states that allow medical cannabis. Findings suggest that legislation may impact the use of certain antiemetics in states with cannabis legislation in place. The presence or absence of legislation regarding medical cannabis use may serve as an early, observable surrogate marker of medical cannabis use in the community. In light of the paucity of clinical trials and observational datasets that capture cannabis use, there remains a tremendous need for the development of methodologies or standardized datasets that appropriately and reliably capture the use of medical cannabis to facilitate research into its clinical application and effect on prescription medication use. Standardizing the reporting and destigmatizing use could eliminate the dependence upon proxy measures as a substitute for more extensive data and go a long way in improving data capture, thus allowing us to generate knowledge and hypotheses from observational data until research conditions improve and allow for expanded clinical trials involving medical cannabis.


Cytochalasan Alkaloids as TRAIL Sensitizers from an Endophytic Fungus Chaetomium sp.
Two new cytochalasans with a rare 6/6/5/5/7 pentacyclic ring system, named chaetoconvosins C-D (1: -2: ), together with two known congeners (3: -4: ), were isolated from the fermentation of an endophytic fungus, Chaetomium sp. SG-01, harbored in the fibrous roots of Schisandra glaucescens Diels. Their structures including the absolute configuration were elucidated by extensive spectroscopic (HRESIMS, NMR, and ECD) and X-ray crystallographic analyses. The TRAIL-resistance-overcoming activity of 1: -4: in a TRAIL-resistant HT29 colorectal cancer cell line was evaluated, which revealed that co-treatment of 1: -4: at 50 µM with TRAIL (150 ng/mL) reduced the HT29 cell viability by 19.0%, 24.1%, 17.9%, and 15.5%, respectively, compared to treatment with 1: -4: alone.


Synergy of the human spine in neutral postures.
The neutral position of the spine is the posture most commonly sustained throughout daily activities. Previous investigations of the spine focused mainly on maximal exertions in various symmetric and asymmetric postures. This report proposes a new synergetic approach for analysis of the spine in neutral postures and evaluates its performance. The model consists of passive components, the osteoligamentous spine, and active components, the spinal muscles. The muscle architecture includes 60 muscles inserting onto both the rib cage and lumbar vertebral bodies. The passive spine is simulated by a finite element model, while kinematic constraints and optimization are used for resolution of a redundant muscle recruitment problem. Although the passive spine alone exhibits little resistance to a vertical load, its load-bearing capacity in neutral posture is significantly enhanced by the muscles, i.e., the passive spine and its muscles must be considered as a synergetic system. The proposed method is used to investigate the response of the spine when the T1 vertebra displaces 40 mm anteriorly and 20 mm posteriorly from its initial position. The sacrum is fixed at all times and the T1 displacements are achieved by the action of muscles. The results suggest that relatively small muscle activations are sufficient to stabilize the spine in neutral posture under the body weight. The results also indicate that muscles attaching onto the rib cage are important for control of the overall spinal posture and maintenance of equilibrium. The muscles inserting onto the lumbar vertebrae are found mainly to enhance the stability of the spine. The proposed method also predicts forces and moments carried by the passive system. Flexion moments ranging from 8000 Nmm to 15,000 Nmm, corresponding to decreases in lordosis of 6 degrees and 7.5 degrees respectively, are found to be carried by the passive spine at the thoracolumbar junction when the T1 vertebra is 40 mm anterior to its initial position.


Iron-substituted cubic silsesquioxane pillared clays: Synthesis, characterization and acid catalytic activity.
Novel pillared structures were developed from the intercalation of iron-substituted cubic silsesquioxanes in a sodium and an acid-activated montmorillonite nanoclay and evaluated as acid catalysts. Octameric cubic oligosiloxanes were formed upon controlled hydrolytic polycondensation of the corresponding monomer (a diamino-alkoxysilane) and reacted with iron cations to form complexes that were intercalated within the layered nanoclay matrices. Upon calcination iron oxide nanoparticles are formed which are located on the silica cubes (pillars) and on the surfaces of the clay platelets. Acid activation of the nanoclay was performed in order to increase the number of acid active sites in the pristine clay and thus increase its catalytic activity. A plethora of analytical techniques including X-ray diffraction, thermal analyses, Fourier transform infrared, electron paramagnetic resonance, Raman, Mössbauer and X-ray photoelectron spectroscopies and porosimetry measurements were used in order to follow the synthesis steps and to fully characterize the final catalysts. The resulting pillared clays exhibit a high specific area and show significant acid catalytic activity that was verified using the catalytic dehydration of isopropanol asa probe reaction.


Modeling forest management effects on water and sediment yield from nested, paired watersheds in the interior Pacific Northwest, USA using WEPP.
The Water Erosion Prediction Project (WEPP) model was applied to seven paired, nested watersheds within the Mica Creek Experimental Watershed located in northern Idaho, USA. The goal was to evaluate the ability of WEPP to simulate the direct and cumulative effects of clear-cutting and partial-cutting (50% canopy removal) on water and sediment yield. WEPP was modified to better represent changes in the Leaf Area Index during post-harvest forest vegetative recovery. Good agreement between simulated and observed streamflow was achieved with minimal to no calibration over a 16-year (1992-2007) period. For the seven watersheds and the entire study period, the overall Nash-Sutcliffe Efficiency (NSE), Kling-Gupta efficiency (KGE), and deviation of runoff volume (DV) between observed and simulated daily streamflow ranged 0.58-0.71, 0.67-0.81, and -4% to 9%, respectively. Good agreement between predicted and observed suspended sediment yield was achieved through the calibration of a single channel critical shear stress parameter. For sediment yield, NSE, KGE, and DV ranged 0.62-0.97, 0.43-0.97, and -2% to 2%, respectively, for the calibration period, and 0.61-0.93, 0.42-0.95, and -24% to 13%, respectively, for the period of model performance assessment. Regression analysis of observed- and WEPP-simulated increase in water and sediment yield following clear-cut treatment was similar; however, the WEPP-simulated increase was lower compared to observations particularly from the partial-cut watershed. The variability in the critical shear parameter for different stream channels in the study watersheds was directly related to the observed mean particle size on the stream bed and suggests that applications of the WEPP model in ungauged basins could potentially set the critical shear parameter based on particle size. Overall, the simulated results demonstrate the potential of WEPP as a modeling tool for forestland watershed management, particularly for estimating the effects of forest harvest on hydrograph fluctuations and consequently, stream sediment transport.


Effects of lorazepam on perceptual integration of visual forms in healthy volunteers.
We tested whether lorazepam (a benzodiazepine) affects perceptual processes involved in the computation of contour information. Subjects matched incomplete forms whose contour was composed of line segments varying in their spacing and in their alignment. An initial centrally displayed object (a reference) was followed by two laterally displayed pictures, a target and a distractor. The distractor was the mirror-reversed version of the target. In one condition, the reference was always an outline drawing of an object. In another condition, the reference was either an outline drawing or an incomplete form. All subjects were run in both conditions. Lorazepam 0.038 mg/kg induced a larger increase in RTs than the placebo and lorazepam 0.026 mg/kg when the spacing between local contour elements was larger than 10.8' arc and when the line segments were not aligned. Performance was improved in the 0.038 mg/kg lorazepam group when subjects started with the condition in which the reference was always an outline drawing. Performance was not correlated with sedation. These results show that lorazepam impairs visual perception. They are interpreted in terms of impaired binding processes, which can be compensated for by the use of stored object representations. This effect is consistent with electrophysiological studies showing that the neuromediator GABA is involved in perceptual processes.


Mitochondrial abnormalities in muscle from vitamin B12-deficient sheep.
Skeletal and cardiac muscles from vitamin B12-deficient sheep were examined. Histochemical studies did not reveal any gross pathological changes in the muscle structure, but there was an abnormal distribution of the product of the NADH-diaphorase reaction. Electron microscopy revealed an abnormal distribution of mitochondria, changes in the number and arrangement of cristae within the mitochondria and the presence of inclusions. The possibility that alterations in mitochondrial morphology are early lesions attributable to metabolic changes in vitamin B12 deficiency is discussed.


Poly(acrylamide-vinylpyridine-N,N'-methylene bisacrylamide) monolithic capillary for in-tube solid-phase microextraction coupled to high performance liquid chromatography.
In-tube solid-phase microextraction (SPME) based on a poly(acrylamide-vinylpyridine-N,N'-methylene bisacrylamide) monolithic capillary was investigated and on-line coupled to HPLC for the determination of trace analytes in aqueous samples. The polymer monolith was conveniently synthesized in a fused silica capillary by in situ polymerization method. Several groups of analytes including non-steroidal anti-inflammatory drugs, phenols, non-peptide angiotensin II receptor antagonists and endocrine disrupting chemicals were extracted by the monolithic capillary. High extraction efficiency was achieved for the analytes investigated and great improvement of the limits of detection were obtained in comparison to that of direct chromatographic analysis and strong hydrophobic and ion-exchange interactions between the analytes and the polymer were confirmed. The newly developed monolithic capillary showed excellent reusability and high stability under extreme pH conditions during extraction. The possibility of applying the established method to water sample analysis was also demonstrated.


Occurrence of Anoplocephala perfoliata infection in horses in Ontario, Canada and associations with colic and management practices.
Infection with the tapeworm Anoplocephala perfoliata has been found to be associated with equine colic in horses in the United Kingdom. Using a matched case-control study design, data collected from 117 pairs of horses in Ontario were examined for evidence of associations between risk of colic and A. perfoliata infection, and between seropositivity to infection and management practices. Cases were horses in southern Ontario diagnosed with colic by local veterinarians, and control horses were from the same stables as cases and were matched by age, breed and gender where possible. Infection status was defined on the basis of positive results upon coprological examination, and/or seropositivity to a 12/13 kDa A. perfoliata secretory protein. Fifty-six percent of the 234 horses were seropositive for A. perfoliata, but eggs were found in samples from only 6% of horses. Horses dependent on pasture for a large part of their diet were significantly more likely to have ELISA optical density levels above 0.600 compared to other horses (odds ratio [OR]=6.38; p=0.029). This finding identified exposure to pasture as an important source of A. perfoliata infection in the horses used in the study. In a subset of 46 pairs of horses for which control horses had no known history of colic, a statistically significant negative association was found between the risk of colic and optical density (OD) levels >0.200-0.600, relative to OD levels < or = 0.090 (OR=0.08; p=0.017). There was no other statistical evidence of an association between the risk of colic and A. perfoliata infection.


Cordycepin exhibits anti-fatigue effect via activating TIGAR/SIRT1/PGC-1α signaling pathway.
Fatigue, a most commonly sub-health condition, may cause people more susceptible to many diseases. Cordycepin, a principal active ingredient from Cordyceps militaris, exerts various pharmacological activities including anti-diabetes, anti-inflammatory, immunomodulatory and antioxidant effects. However, the anti-fatigue effect of cordycepin and specific mechanism remained unclear. This study aimed to investigate the beneficial effect of cordycepin on physical fatigue and elucidate the potential mechanism. 20 mg/kg, 40 mg/kg of cordycepin and 500 mg/kg taurine were respectively treated to mice for 28 days before weight-loaded swimming test. The results revealed that cordycepin significantly prolonged the weight-loaded swimming time of mice. Meanwhile, cordycepin decreased the levels of lactic acid, blood uric nitrogen, and malondialdehyde, and increased the contents of superoxide dismutase, glutathione, nicotinamide adenine dinucleotide phosphate, hepatic glycogen, muscle glycogen and ATP. The metabolomic study by GC-MS showed that eight biomarkers were found in livers, including L-lactic acid, L-asparagine, 3-phosphoglyceric acid, inosine, D-galactose, L-tyrosine, glyceric acid and L-threonine. There were seven biomarkers in gastrocnemius, including D-ribose-5-phosphate, acetic acid, propionic acid, butyric acid, palmitic acid, oxaloacetic acid and citric acid. The results of metabolomics indicated that cordycepin might relieve fatigue by regulating energy metabolism and pentose phosphate pathway. Furthermore, we found cordycepin significantly enhanced the protein levels of TIGAR, SIRT1, PGC-1α, NRF1 and TFAM in gastrocnemius of weight-loaded swimming mice. Taken together, the present study demonstrated that cordycepin possessed an anti-fatigue effect via activating TIGAR/SIRT1/PGC-1α signaling pathway. Our study indicated that cordycepin may be a potentially efficient candidate for fatigue.


Tissue reactions to two root canal sealers containing formaldehyde.
Tissue reaction to root fillings using either Endomethasone or N2 was investigated in the premolar teeth of dogs. Periapical inflammation was frequently observed, but of greater significance was the universal evidence of ankylosis and the accompanying resorption of teeth filled with N2. One tooth filled with Endomethasone also exhibited this condition. The results of this study do not support the use of these root canal sealers that contain formaldehyde.


Poststroke depression and psychosis.
Stroke is capable of producing a varied spectrum of neurobehavioral syndromes that may come to the attention of the mental health professional evaluating psychiatric symptoms in elderly individuals. The neurobehavioral effects may include affective or psychotic symptoms and may occur immediately after the stroke or months to years later. The presence of underlying (or pre-existing) brain disease may have an adverse effect on the resolution of the neuropsychiatric symptoms. Although there are no treatment response studies in the area of psychosis following stroke, the response of poststroke depression to antidepressants makes attempted pharmacologic treatment of symptoms justified.


Evidence for a role of endorphins in stress- and suckling-induced prolactin release in the rat.
Injection of the opiate antagonist naloxone completely prevented the rise of serum prolactin induced by ether stress in intact male rats. Naloxone also led to a 50--95% inhibition of the marked elevation of plasma prolactin levels induced by suckling. These data suggest that endogenous opiates (endorphins) are involved in the stimulation of prolactin release induced by both stress and suckling in the rat.


YY1 and Sp1 activate transcription of the human NDUFS8 gene encoding the mitochondrial complex I TYKY subunit.
Complex I is the most complicated of the multimeric enzymes that constitute the mitochondrial respiratory chain. It is encoded by both mitochondrial and nuclear genomes. We have previously characterized the human NDUFS8 gene that encodes the TYKY subunit. This essential subunit is thought to participate in the electron transfer and proton pumping activities of complex I. Here, we have analyzed the transcriptional regulation of the NDUFS8 gene. Using primer extension assays, we have identified two transcription start sites. The basal promoter was mapped to a 247 bp sequence upstream from the main transcription start site by reporter gene analysis in HeLa cells and in differentiated or non-differentiated C2C12 cells. Three Sp1 sites and one YY1 site were identified in this minimal promoter. Through gel shift analysis, all sites were shown to bind to their cognate transcription factors. Site-directed mutagenesis revealed that the YY1 site and two upstream adjacent Sp1 sites drive most of the promoter activity. This work represents the first promoter analysis for a complex I gene. Together with previous studies, our results indicate that YY1 and Sp1 control the expression of genes encoding proteins that are involved in almost all steps of the oxidative phosphorylation metabolism.


Fear of crime and psychological and physical abuse associated with ill health in a Swedish population aged 65-84 years.
To assess the association between fear of crime and/or psychological and/or physical abuse in relation to self-reported physical and psychological health, using a large representative sample of elderly women and men in Sweden. Cross-sectional national survey. Data were taken from a nationwide representative public health survey (2006). Men and women between the ages of 65 and 84 years were selected for the present analyses (4386 men and 4974 women). The response rate for this age group was 59% for men and 70% for women. Psychological and physical abuse against elderly women and men led to higher odds ratios for negative health outcomes, independently of socio-economic status. Strong correlation was found between psychological abuse and negative health outcomes in both men and women, while the correlation was less strong for physical abuse, especially among women. The men had high odds ratios for suicidal thoughts and even for attempted suicide in connection with physical and psychological abuse and fear of crime. The study provides representative results addressing an extensive negative health outcome panorama caused by fear of crime and exposure to abuse.


Reliability and accuracy of telemedicine-based shoulder examinations.
Telemedicine has become a critical component in the evaluation and management of patients with shoulder pathology. However, the interobserver reliability of findings on virtual physical examination relative to in-person evaluation is unclear. The purpose of this study was to determine the reliability of prerecorded video telemedicine for the evaluation of shoulder pathology compared with traditional in-person physical examination. New patients with unilateral shoulder pain presenting to a single-surgeon shoulder clinic were recruited between July and November 2020. In 1 visit, patients were evaluated with standardized in-person and video-guided telemedicine physical examinations in randomized order. Patients were evaluated for range of motion (ROM) and symptoms including pain, weakness, and apprehension. The telemedicine examination was recorded and consisted of a video guide displaying self-directed shoulder examination maneuvers that patients performed during remote coaching by an independent non-physician observer. The in-person physical examination was performed by the treating physician. The telemedicine videos were evaluated by two independent observers for interobserver reliability. The treating physician subsequently evaluated the telemedicine videos after a minimum two-month washout period for intraobserver reliability and intra-platform reliability. Interobserver and intraobserver reliability analyses were conducted using Kuder-Richardson formula 20 (KR-20). Specificity and likelihood ratios were calculated with P < .05 representing statistical significance. A total of 32 patients (17 male and 15 female patients; average age, 50.2 ± 16.2 years) were included in the analysis. Overall Kuder-Richardson formula 20 (KR-20) reliability across 40 physical examination maneuvers was 0.391 ± 0.332 (76.4% ± 15.4% agreement) between the in-person and telemedicine examinations. Telemedicine maneuvers examining ROM limitations had the highest degree of reliability, sensitivity, specificity, and likelihood of also producing a positive finding on the in-person examination (0.700 ± 0.114, 66.5%, 81.0%, and 6.06, respectively). Telemedicine maneuvers identifying apprehension associated with glenohumeral instability were found to have the lowest reliability, sensitivity, and likelihood of producing a positive finding on the in-person examination (0.170 ± 0.440, 23.5%, and 0.518, respectively). All patients were satisfied with their telemedicine experience. The overall reliability of a non-physician-directed video-guided telemedicine examination ranged from unacceptable to good. Shoulder ROM limitations identified during the telemedicine examinations were found to be the most reliable, whereas evaluations of instability were found to be the least reliable. Although initial telemedicine evaluation by a non-physician may be appropriate for ROM evaluation, in-person physician evaluation is recommended to confirm suspected diagnoses, especially if clinical concern for shoulder instability exists. Alternative methods of telemedicine delivery should be explored to improve the reliability of self-directed physical examination maneuvers.


The resistance of G mouse fibroblasts to murine leukemia virus infection.
In vitro resistance of G mouse cells was not expressed in the initial cycle of MuLV infection but in the propagation of virus to the surrounding cells.


Morphine increases synchronous ventilation in preterm infants.
To examine the short-term cardiorespiratory effects of intravenous morphine infusion in ventilated preterm infants. A randomized double-blind placebo-controlled trial in a neonatal intensive care unit. Twenty-six preterm infants (29-36 weeks gestation) with hyaline membrane disease requiring ventilatory assistance on the first day after birth were included in the study. A loading dose of morphine 100 micrograms/kg over 30 min followed by a continuous intravenous infusion at 10 micrograms/kg per hour was given. Primary measures were heart rate, blood pressure, respiratory rate and interaction of spontaneous respiration with mechanical ventilation. Secondary measures were durations of oxygen therapy, ventilator therapy and hospitalization as well as incidence of bronchopulmonary dysplasia, periventricular haemorrhage and pneumothorax. Morphine-treated infants spent a significantly greater percentage of total ventilated time breathing in synchrony with their ventilators (median [IQ] = 72[58-87] vs 31[17-51]%; P = 0.0008). Heart rate and respiratory rate, but not blood pressure, were reduced in morphine-treated infants. Duration of oxygen therapy was reduced (median [IQ] = 4.5[3-7] vs 8[4.75-12.5] days; P = 0.046). Intravenous morphine infusion increases synchronicity of spontaneous and ventilator-delivered breaths in preterm infants. Morphine reduces heart rate and respiratory rate without reducing blood pressure, and may help to reduce duration of oxygen therapy in preterm infants with hyaline membrane disease.


DNA-histone complexes as ligands amplify cell penetration and nuclear targeting of anti-DNA antibodies via energy-independent mechanisms.
We have generated three monoclonal cell-penetrating antibodies (CPAbs) from a non-immunized lupus-prone (NZB × NZW)F1 mouse that exhibited high anti-DNA serum titres. These CPAbs are polyreactive because they bind to DNA and other cellular components, and localize mainly in the nucleus of HeLa cells, albeit with a distinct nuclear labelling profile. Herein, we have examined whether DNA-histone complexes (DHC) binding to CPAbs, before cell entry, could modify the cell penetration of CPAbs or their nuclear staining properties. By applying confocal microscopy and image analysis, we found that extracellular binding of purified CPAbs to DHC significantly enhanced their subsequent cell-entry, both in terms of percentages of positively labelled cells and fluorescence intensity (internalized CPAb amount), whereas there was a variable effect on their nuclear staining profile. Internalization of CPAbs, either alone or bound to DHC, remained unaltered after the addition of endocytosis-specific inhibitors at 37° or assay performance at 4°, suggesting the involvement of energy-independent mechanisms in the internalization process. These findings assign to CPAbs a more complex pathogenetic role in systemic lupus erythematosus where both CPAbs and nuclear components are abundant.


Ultrastructural and cytological changes in the muscle fibers of the pectoralis of the giant Canada goose (Branta canadensis maxima) in disuse atrophy during molt.
Adult male Branta canadensis maxima were collected from a nonmigratory feral population during their premolt, molt and postmolt phases. Lean dry weight of the pectoralis muscle decreased significantly (p less than or equal to 0.0001) during molt, as a result of disuse atrophy. Histochemical analysis revealed that the region of the pectoralis muscle sampled consisted of Red (fast-twitch oxidative-glycolytic) and White (fast-twitch glycolytic) muscle fiber types, in an approximate ratio of 9 to 1. There was no significant (p = 0.1238) difference in the relative percentages of the two fiber types during the three periods of study. There was, however, a significant decrease in mean cross-sectional area of both Red (p less than or equal to 0.0194) and White (p less than or equal to 0.0001) fibers during molt. Red and White fiber areas were strongly correlated with each other during molt (r2 = 0.76, p = 0.0010) and postmolt (r2 = 0.70, p = 0.0052), but not during premolt (r2 = 0.02, p = 0.7626). The latter finding may be related to fiber-type specific hypertrophy in premolt breeding males. Analysis of ultrastructure revealed that there was a significant (p = 0.0003) decrease in the mean myofibrillar cross-sectional area, and a significant increase in both the density (p = 0.0227) and total number (p = 0.0058) of myofibrils within the muscle fibers of the molting birds. These results indicate that the myofibrils split longitudinally during molt-associated disuse atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)


Improving the thermal conductivity of epoxy composites using a combustion-synthesized aggregated β-Si3N4 filler with randomly oriented grains.
Electrically insulating and thermally conductive polymer matrix composites are desirable for industry applications as they improve the reliability of high-performance electronic devices, particularly via heat dissipation in devices loaded with several electronic components. In this study, an aggregated β-Si3N4 filler with randomly oriented grains was produced via combustion synthesis to improve the thermal conductivity of epoxy composites. The thermal conductivities of the prepared composites were investigated as a function of the filler content, and the values were compared to those of composites loaded with commercial β-Si3N4 (non-aggregated). Negligible difference was observed in the thermal conductivities of both types of composites when the Si3N4 content was below 40 vol%; however, above 40 vol%, the aggregated β-Si3N4 filler-loaded composites showed higher thermal conductivities than the commercial β-Si3N4-loaded composites. The aggregated β-Si3N4 filler-loaded composites exhibited isotropic thermal conductivities with a maximum value of 4.7 W m-1 K-1 at 53 vol% filler content, which is approximately 2.4 times higher than that of the commercial β-Si3N4-loaded composites, thereby suggesting that the morphology of the aggregated filler would be more efficient than that of the commonly used non-aggregated filler in enhancing the thermal conductivity of a polymer matrix composite.


Draft Genome Sequence of a Gordonia sp. Isolated from the Soil of a Red Alder Plant.
A Gordonia species was cultured from soil of a red alder (Alnus rubra) plant. Here we present the assembled and annotated genome sequence to aid investigations into the potential of this organism as a symbiont and comparative studies of the genus Gordonia.


Hemodynamics and function of resistance arteries in healthy persons and end stage renal disease patients.
Cardiovascular disease is the leading cause of death in patients with end stage renal disease (ESRD). The vasodilator mechanisms in small resistance arteries are in earlier studies shown to be reduced in patients with end stage renal disease. We studied whether endothelium dependent vasodilatation were diminished in ESRD patients and the interaction between the macro- and microcirculation. Eleven patients with ESRD had prior to renal transplant or insertion of peritoneal dialysis catheter measured pulse wave velocity. During surgery, a subcutaneous fat biopsy was extracted. Resistance arteries were then dissected and mounted on a wire myograph for measurements of dilator response to increasing concentrations of acetylcholine after preconstriction with noradrenaline. Twelve healthy kidney donors served as controls. Systolic blood pressure was elevated in patients compared to the healthy controls; no difference in the concentration of asymmetric dimethyl arginine was seen. No significant difference in the endothelium dependent vasodilatation between patients and controls was found. Correlation of small artery properties showed an inverse relationship between diastolic blood pressure and nitric oxide dependent vasodilatation in controls. Pulse pressure was positively correlated to the total endothelial vasodilatation in patients. A negative association between S-phosphate and endothelial derived hyperpolarisation-like vasodilatation was seen in resistance arteries from controls. This study finds similar vasodilator properties in kidney patients and controls. However, correlations of pulse pressure and diastolic blood pressure with resistance artery function indicate compensating measures in the microcirculation during end stage renal disease.


Association of Medicaid Expansion With Mortality Disparity by Race and Ethnicity Among Patients With De Novo Stage IV Breast Cancer.
Patients who are uninsured and belong to racial and ethnic minority groups or have low socioeconomic status have suboptimal access to health care, likely affecting outcomes. The association of the Affordable Care Act's Medicaid expansion with survival among patients with metastatic breast cancer is unknown. To examine the association between Medicaid expansion and mortality disparity among patients with de novo stage IV breast cancer. Cross-sectional, population-based study of survival using Cox proportional hazards regression and difference-in-difference (DID) analysis of data from the National Cancer Database and patients diagnosed as having de novo stage IV breast cancer between January 1, 2010, and December 31, 2016, residing in states that underwent Medicaid expansion on January 1, 2014. The preexpansion period was January 1, 2010, to December 31, 2013; the postexpansion period was January 1, 2014, to December 31, 2016. Data were analyzed between September 4, 2020, and November 16, 2021. Comparison of survival improvement between patients of racial and ethnic minority groups and White patients in the preexpansion and postexpansion periods. Because of small numbers in the specific racial and ethnic minority groups, these patients were combined into 1 category for comparisons. Overall survival (OS) and 2-year mortality rate. Among 9322 patients included (mean [SD] age, 55 [7] years), 5077 were diagnosed in the preexpansion and 4245 in the postexpansion period. The racial and ethnic minority group comprised 2545 (27.3%), which included 500 (5.4%) Hispanic (any race), 1515 (16.3%) non-Hispanic Black, and 530 (5.7%) non-Hispanic other including 25 (0.3%) American Indian or Alaska Native, 357 (3.8%) Asian or Pacific Islander, and 148 (1.6%) unknown, and 6777 (72.7%) were in the White patient group. In the preexpansion period, White patients had increased OS compared with patients of racial and ethnic minority groups (adjusted hazard ratio [aHR], 1.22; 95% CI, 1.10-1.35); this difference was not observed in the postexpansion period (aHR, 0.96; 95% CI, 0.86-1.08). A reduction in 2-year mortality was observed between the preexpansion and postexpansion periods (32.2% vs 26.0%). The adjusted 2-year mortality decreased from 40.6% to 36.3% among White patients and from 45.6% to 35.8% among patients of racial and ethnic minority groups (adjusted DID, -5.5%; 95% CI, -9.5 to -1.6; P = .006). Among patients in the lowest income quartile (n = 1510), patients of racial and ethnic minority groups had an increased risk of death in the preexpansion period (aHR, 1.28; 95% CI, 1.01-1.61) but lower risk in the postexpansion period (aHR, 0.75; 95% CI, 0.59-0.95). In this subset of patients, those of racial and ethnic minority groups had a greater reduction in 2-year mortality compared with White patients (adjusted DID, -12.8%; 95% CI, -22.2 to -3.5; P = .007). In this cross-sectional study, survival differences observed between patients of racial and ethnic minority groups and White patients in the preexpansion period were no longer present in the postexpansion period. A greater reduction in 2-year mortality was observed among patients of racial and ethnic minority groups compared with White patients. These results suggest that policies aimed at improving equity and increasing access to health care may reduce racial and ethnic disparities in breast cancer outcomes.


Influence of catheter orientation on lesion formation in bovine myocardium by using an open-irrigated laser ablation catheter.
Lesion sizes and quality are crucial for successful catheter ablation procedures. We sought to test the influence of catheter orientation towards the endocardial surface on lesion formation in bovine myocardium by using an open-irrigated laser ablation catheter. Continuous wave 1064-nm laser catheter applications at 15 W (4.5 W/mm²)/30 s, (135 J/mm²), irrigation flow 30 mL/min, were aimed at the left ventricular endocardial surface of bovine myocardium. The catheter was kept in vertical, in slanting (67.5°, 45°, 22.5°), and in flat positions; in flat position, also 60 s of radiation times were applied (n = 10, each). Lesions were evaluated morphometrically. Maximum depth of lesion was achieved with the catheter in a vertical orientation. Catheter inclination of <22.5 showed a highly significant decrease of lesion depth from 5.6 ± 1.1 to 3.7 ± 0.5 mm (p = 0.0001). In a flat catheter position, laser radiation of 30 s achieved the smallest lesions. However, after 60 s of radiation, the flat lesions were similar in depth (p = 087) and were larger in width (p = 0.0004) and in volumes (p = 0.0025) as compared to the lesions achieved with the catheter in vertical position after 30 s of radiation. Steam-pop with intramural cavitation or tissue vaporization with crater formation did not occur. Longer radiation times can achieve larger lesions regardless of catheter orientation. Catheter orientation is not a major determinant for laser ablation lesion size and quality, and a steerable support may not be needed when using the open-irrigated electrode-laser mapping and ablation (ELMA) catheter RytmoLas.


A novel in vitro flow system for changing flow direction on endothelial cells.
Atherosclerotic plaques localize to regions of flow disturbance, i.e. bifurcations, branch points and regions of high curvature. Shear stress in these regions can be multi-directional due to complex flow patterns such as time-varying vortices. However, commonly used in vitro flow models are incapable of changing flow orientation to any direction other than the reverse. We have developed a novel in vitro flow system to enable changes in flow direction to any angle. When cells were pre-aligned in laminar shear, and then rotated 90°, cells re-aligned over 24 h. Re-alignment involved actin remodeling by gradual rotation of actin stress fibers. This device will enable that analysis of how endothelial cells sense changes in flow direction as occur in vivo.


Genes involved in the formation and assembly of rhizobial cytochromes and their role in symbiotic nitrogen fixation.
Rhizobia fix nitrogen in a symbiotic association with leguminous plants and this occurs in nodules. A low-oxygen environment is needed for nitrogen fixation, which paradoxically has a requirement for rapid respiration to produce ATP. These conflicting demands are met by control of oxygen flux and production of leghaemoglobin (an oxygen carrier) by the plant, coupled with the expression of a high-affinity oxidase by the nodule bacteria (bacteroids). Many of the bacterial genes encoding cytochrome synthesis and assembly have been identified in a variety of rhizobial strains. Nitrogen-fixing bacteroids use a cytochrome cbb3-type oxidase encoded by the fixNOQP operon; electron transfer to this high-affinity oxidase is via the cytochrome bc1 complex. During free-living growth, electron transport from the cytochrome bc1 complex to cytochrome aa3 occurs via a transmembrane cytochrome c (CycM). In some rhizobia (such as Bradyrhizobium japonicum) there is a second cytochrome oxidase that also requires electron transport via the cytochrome bc1 complex. In parallel with these cytochrome c oxidases there are quinol oxidases that are expressed during free-living growth. A cytochrome bb3 quinol oxidase is thought to be present in B. japonicum; in Rhizobium leguminosarum, Rhizobium etli and Azorhizobium caulinodans cytochrome d-type oxidases have been identified. Spectroscopic data suggest the presence of a cytochrome o-type oxidase in several rhizobia, although the absence of haem O in B. japonicum may indicate that the absorption attributed to cytochrome o could be due to a high-spin cytochrome b in a cytochrome bb3-type oxidase. In some rhizobia, mutation of genes involved in cytochrome c assembly does not strongly affect growth, presumably because the bacteria utilize the cytochrome c-independent quinol oxidases. In this review, we outline the work on various rhizobial mutants affected in different components of the electron transport pathways, and the effects of these mutations on symbiotic nitrogen fixation and free-living growth.


Causes of false negatives in technetium-99 m methoxyisobutylisonitrile scintigraphy for hyperparathyroidism: influence of size and cysts in parathyroid lesions.
The aim of this study was to elucidate the causes of false-negative cases of technetium-99 m methoxyisobutylisonitrile scintigraphy (MIBI) for hyperparathyroidism. Consecutive MIBI examinations performed in 154 patients between April 2011 and March 2017 were retrospectively reviewed. Sensitivities of MIBI, CT and US were calculated. The effects of serum calcium, phosphorus, PTH, weight of parathyroid lesions, use of NSAIDs and Ca-channel blocker (CCB), presence of cyst in parathyroid lesions, and a number of lesions observed by MIBI were investigated. Seventy-nine patients (21 men and 58 women), ranging from 18 to 88 years of age (mean ± SD: 57.6 ± 15.3 years), who underwent parathyroidectomy, were included. MIBI and preoperative US were performed in the 79 patients and single-phase parenchymal contrast-enhanced CT (CE-CT) was performed in 55 patients. A total of 120 parathyroid proliferative nodules were detected by MIBI and US, and 92 lesions were detected by CE-CT. In the lesion base, MIBI detected 82 out of the 120 lesions (sensitivity = 68.3%), US detected 103 out of the 120 lesions (sensitivity = 85.8%), CE-CT detected 63 out of the 92 lesions (sensitivity = 68.5%), and MIBI plus CE-CT detected 72 of the 92 lesions (sensitivity = 78.3%). A significant difference in the sensitivity was found between US and MIBI (P < 0.01), and between US and CT (P < 0.01). In the patient base, MIBI detected 67 out of the 79 patients (sensitivity = 84.8%), US detected 74 out of the 79 patients (sensitivity = 93.7%), CE-CT detected 45 out of the 55 patients (sensitivity = 81.8%), and MIBI plus CE-CT detected 52 out of the 55 patients (sensitivity = 94.5%). No significant difference was observed in any of the comparisons. A significant difference was observed in lesion weight (P < 0.01), single or multiple lesions (P = 0.02), and presence of cyst (P < 0.01) between the MIBI false-negative (n = 38) and the true-positive groups (n = 82). The presence of cyst in parathyroid proliferative lesions as well as small size and multiple number of parathyroid lesions contribute to false negative in parathyroid MIBI scan.


The location of antigenic sites on ferritin molecules.
Immunoreactivities of peptides purified after cleavage of human liver apoferritin are reported and discussed in relation to the known 3-dimensional and primary structures of homologous apoferritins. These studies point to 3 antigenic sites occupying continuous inter-helical regions of the polypeptide chains which lie on the surface of the apoferritin molecule. Other antigenic regions may encompass amino acids remote in the primary structure or belonging to different subunits.


Activity of Lactobacillus crispatus isolated from vaginal microbiota against Mycobacterium tuberculosis.
Tuberculosis, an infectious disease, is caused by Mycobacterium tuberculosis. It remains a significant public health issue around the globe, causing about 1.8 million deaths every year. Drug-resistant M. tuberculosis, including multi-drug-resistant (MDR), extremely-drug-resistant (XDR), and totally drug-resistant (TDR) M. tuberculosis, continues to be a threat to public health. In the case of antibiotic-resistant tuberculosis, the treatment effect of conventional antibiotics is low. Side effects caused by high doses over a long period are causing severe problems. To overcome these problems, there is an urgent need to develop a new anti-tuberculosis drug that is different from the existing compound-based antibiotics. Probiotics are defined as live microorganisms conferring health benefits. They can be potential therapeutic agents in this context as the effectiveness of probiotics against different infectious diseases has been well established. Here, we report that Lactobacillus crispatus PMC201 shows a promising effect on tuberculosis isolated from vaginal fluids of healthy Korean women. Lactobacillus crispatus PMC201 reduced M. tuberculosis H37Rv under co-culture conditions in broth and reduced M. tuberculosis H37Rv and XDR M. tuberculosis in macrophages. Lactobacillus crispatus PMC201 was not toxic to a guinea pig model and did not induce dysbiosis in a human intestinal microbial ecosystem simulator. Taken together, these results indicate that L. crispatus PMC201 can be a promising alternative drug candidate in the current tuberculosis drug regime. Further study is warranted to assess the in vivo efficacy and confirm the mode of action of L. crispatus PMC201.


The impact of various carbon nanomaterials on the morphological, behavioural, and biochemical parameters of rainbow trout in the early life stages.
With the increasing production and the number of potential applications of carbon nanomaterials, mainly from the graphene family, their release into the natural environment, especially to aquatic ecosystems, is inevitable. The aim of the study was to determine the effects of various carbon nanomaterials (graphene nanoflakes (GNF), graphene oxide (GO), reduced graphene oxide (RGO) and silicon carbide nanofibers (NFSiC) in the concentration of 4 mg L-1 on the early life stages of the rainbow trout Oncorhynchus mykiss. The survival rates of O. mykiss were not affected after 36 days of exposure to studied materials, except for RGO, which caused significant mortality of both embryos and larvae compared to the control conditions. Larvae exposed to GO and NFSiC were characterized by a smaller standard body length at hatch, whereas at the end of the experiment, the growth of fish exposed to all materials was accelerated, especially in GO and RGO treatment, in which higher body weight and length were accompanied by lower volume of the yolk sac. Neither the markers of the oxidative damage nor the antioxidant enzymes activities were significantly affected in embryos, newly hatched larvae and larvae after 26-day exposure to studied carbon nanomaterials. Also, no neurotoxic effect expressed by the activity of the whole-body acetylcholinesterase was observed. Nevertheless, the significant increase in the velocity and the overall activity of larvae exposed to GNF (not investigated after exposure to other materials) must be highlighted. The most pronounced effect of RGO might be connected with its large particle size, sharp edges, and the presence of TiO2 nanoparticles. The results indicate for the first time that various carbon nanomaterials potentially released into aquatic ecosystems may have serious developmental implications for the early life stages of salmonid fish.


Evaluation of the effect of ototopical neomycin on spiral ganglion cell density in the guinea pig.
The development of a reproducible unilateral deafness animal model was the primary objective of this study. Because of its importance in the function of cochlear prostheses, the status of the VIIIth nerve was used as the measure of deafness. The effect of a concentrated neomycin solution applied locally to the middle ear of the guinea pig was evaluated. Spiral ganglion cell survival was quantitated at 1, 2, 4, 6 and 10 weeks after exposure. Although the intermediate time periods showed moderate inter-animal variability, by ten weeks, consistent spiral ganglion cell loss was seen with maximum cell loss at the extreme apex (18.8% of control) and base (30.3% of control) and maximum cell survival in the lower middle turns of the cochlear spiral (53% of control).


A urea-assisted template method to synthesize mesoporous N-doped CeO2 for CO2 capture.
Novel mesoporous N-doped CeO2 has been prepared via a simple urea-assisted template method using cerium nitrate as precursor. The synthesized mesoporous N-doped CeO2 applied as an adsorbent exhibits significantly enhanced CO2 adsorption performance compared with undoped mesoporous CeO2.


Binding of Paracoccidioides brasiliensis to laminin through surface glycoprotein gp43 leads to enhancement of fungal pathogenesis.
Extracellular matrix protein laminin binds specifically to yeast forms of Paracoccidioides brasiliensis and enhances adhesion of the fungus to the surface of epithelial Madin-Darby canine kidney cells in vitro. Immunoblotting of fungal extracts showed that the gp43 glycoprotein is responsible for adhesion. This was confirmed by binding assays using purified gp43, with a Kd of 3.7 nM. The coating of P. brasiliensis yeast forms with laminin before injection into hamster testicles enhanced the fungus virulence, resulting in a faster and more severe granulomatous disease. These results indicate that interaction of fungi with extracellular matrix elements may constitute a basis for the evolution of fungal infection toward regional spreading and dissemination.


Ultraviolet-induced apoptosis in embryonic stem cells in vitro.
Embryonic stem (ES) cells, and the inner cell mass from which they are derived, are hypersensitive to DNA damage and appear to have specific cellular defense systems for DNA repair and the elimination of damaged cells. These mechanisms differ from somatic cells and are vital to minimize developmental defects that would potentially result from the continued proliferation and differentiation of abnormal cells into adult cell lineages. Although the DNA damage-induced signaling cascades activated in these cells are known to include p38 and c-Jun N-terminal protein kinase mitogen-activated protein kinase pathways and activation of a variety of transcription factors, including p53, nuclear factor-kappaB, and activator protein-1, the nature of the specific mechanisms unique to these cells remains to be elucidated. Here, we describe the use of homozygous knockout ES cells to investigate the role of Ets1 in the response to DNA damage in these cells. These studies demonstrate that Ets1 is required for optimal p53 function in this response and further demonstrate the potential for knockout ES cells to elucidate the role of specific genes in early embryonic cell responses.


Keratin proteins and carcinoembryonic antigen in synovial sarcomas: an immunohistochemical study of 24 cases.
Twenty-four synovial sarcomas were examined for the presence of keratin proteins by an indirect immunoperoxidase method with paraffin-embedded tissues. Keratin proteins were identified in 16 of 24 cases (67 per cent). Both the pseudoglandular and spindle cell areas of all eight of the biphasic synovial sarcomas and the spindle cells of eight of the 16 monophasic synovial sarcomas contained keratin proteins. In spindle cell areas, staining was observed in single cells and small cords and clusters of cells in the absence of cleft formation or other evidence of a pseudoglandular component. The predominant cytologic staining pattern in all cases was peripheral, with localization of staining to the cell membrane or adjacent areas, but diffuse and focal cytoplasmic staining patterns were also observed. No staining for keratin proteins was seen in 101 control cases, including 52 sarcomas of various types. Carcinoembryonic antigen was also identified in four of the 24 synovial sarcomas by an indirect immunoperoxidase technique. The identification of keratin proteins may be helpful in the pathologic diagnosis of synovial sarcoma, particularly the spindle cell monophasic variant.


Digital Allergy Card: Design and Users' Perceptions.
This paper presents the design and the users' perceptions of a Digital Allergy Card for recording, sharing and tracing information on drug allergies.


Motion-induced disturbance of auditory-motor synchronization and its modulation by transcranial direct current stimulation.
The timing of personal movement with respect to external events has previously been investigated using a synchronized finger-tapping task with a sequence of auditory or visual stimuli. While visuomotor synchronization is more accurate with moving stimuli than with stationary stimuli, it remains unclear whether the same principle holds true in the auditory domain. Although the right inferior-superior parietal lobe (IPL/SPL), a center of auditory motion processing, is expected to be involved in auditory-motor synchronization with moving sounds, its functional relevance has not yet been investigated. The aim of the present study was thus to clarify whether horizontal auditory motion affects the accuracy of finger-tapping synchronized with sounds, as well as whether the application of transcranial direct current stimulation (tDCS) to the right IPL/SPL affects this. Nineteen healthy right-handed participants performed a task in which tapping was synchronized with both stationary sounds and sounds that created apparent horizontal motion. This task was performed before and during anodal, cathodal and sham tDCS application to the right IPL/SPL in separate sessions. The time difference between the onset of the sounds and tapping was larger with apparently moving sounds than with stationary sounds. Cathodal tDCS decreased this difference, anodal tDCS increased the variance of the difference and sham stimulation had no effect. These results supported the hypothesis that auditory motion disturbs efficient auditory-motor synchronization and that the right IPL/SPL plays an important role in tapping in synchrony with moving sounds via auditory motion processing.


DNA barcoding analysis and phylogenetic relationships of tree species in tropical cloud forests.
DNA barcoding is a useful tool for species identification and phylogenetic construction. But present studies have far reached a consistent result on the universality of DNA barcoding. We tested the universality of tree species DNA barcodes including rbcL, matK, trnH-psbA and ITS, and examined their abilities of species identification and phylogenetic construction in three tropical cloud forests. Results showed that the success rates of PCR amplification of rbcL, matK, trnH-psbA and ITS were 75.26% ± 3.65%, 57.24% ± 4.42%, 79.28% ± 7.08%, 50.31% ± 6.64%, and the rates of DNA sequencing were 63.84% ± 4.32%, 50.82% ± 4.36%, 72.87% ± 11.37%, 45.15% ± 8.91% respectively, suggesting that both rbcL and trnH-psbA are universal for tree species in the tropical cloud forests. The success rates of species identification of the four fragments were higher than 41.00% (rbcL: 41.50% ± 2.81%, matK: 42.88% ± 2.59%, trnH-psbA: 46.16% ± 5.11% and ITS: 47.20% ± 5.76%), demonstrating that these fragments have potentiality in species identification. When the phylogenetic relationships were built with random fragment combinations, optimal evolutionary tree with high supporting values were established using the combinations of rbcL + matK + trnH-psbA in tropical cloud forests.


Partially pre-calculated weights for the backpropagation learning regime and high accuracy function mapping using continuous input RAM-based sigma-pi nets.
In this article we present a methodology that partially pre-calculates the weight updates of the backpropagation learning regime and obtains high accuracy function mapping. The paper shows how to implement neural units in a digital formulation which enables the weights to be quantised to 8-bits and the activations to 9-bits. A novel methodology is introduced to enable the accuracy of sigma-pi units to be increased by expanding their internal state space. We, also, introduce a novel means of implementing bit-streams in ring memories instead of utilising shift registers. The investigation utilises digital "Higher Order" sigma-pi nodes and studies continuous input RAM-based sigma-pi units. The units are trained with the backpropagation learning regime to learn functions to a high accuracy. The neural model is the sigma-pi units which can be implemented in digital microelectronic technology. The ability to perform tasks that require the input of real-valued information, is one of the central requirements of any cognitive system that utilises artificial neural network methodologies. In this article we present recent research which investigates a technique that can be used for mapping accurate real-valued functions to RAM-nets. One of our goals was to achieve accuracies of better than 1% for target output functions in the range Y epsilon [0,1], this is equivalent to an average Mean Square Error (MSE) over all training vectors of 0.0001 or an error modulus of 0.01. We present a development of the sigma-pi node which enables the provision of high accuracy outputs. The sigma-pi neural model was initially developed by Gurney (Learning in nets of structured hypercubes. PhD Thesis, Department of Electrical Engineering, Brunel University, Middlessex, UK, 1989; available as Technical Memo CN/R/144). Gurney's neuron models, the Time Integration Node (TIN), utilises an activation that was derived from a bit-stream. In this article we present a new methodology for storing sigma-pi node's activations as single values which are averages. In the course of the article we state what we define as a real number; how we represent real numbers and input of continuous values in our neural system. We show how to utilise the bounded quantised site-values (weights) of sigma-pi nodes to make training of these neurocomputing systems simple, using pre-calculated look-up tables to train the nets. In order to meet our accuracy goal, we introduce a means of increasing the bandwidth capability of sigma-pi units by expanding their internal state-space. In our implementation we utilise bit-streams when we calculate the real-valued outputs of the net. To simplify the hardware implementation of bit-streams we present a method of mapping them to RAM-based hardware using 'ring memories'. Finally, we study the sigma-pi units' ability to generalise once they are trained to map real-valued, high accuracy, continuous functions. We use sigma-pi units as they have been shown to have shorter training times than their analogue counterparts and can also overcome some of the drawbacks of semi-linear units (Gurney, 1992. Neural Networks, 5, 289-303).


Single-port robotic-assisted ureteral reconstruction for management of strictures after renal transplantation.
Ureteral strictures are a common and often challenging complication of renal transplantation. The use of single-port (SP) robotic-assisted laparoscopic surgery is a novel approach in the management of these patients. Here we describe 3 patients with stricture of the transplant ureter causing hydronephrosis and allograft dysfunction, whose ureteral reconstructions were successfully performed using the SP robotic-assisted laparoscopic approach. Two patients underwent transplant-to-native ureteroureterostomy and 1 patient underwent ureteroneocystostomy. We demonstrate that the use of concurrent ureteroscopy and near-infrared fluorescence enables safe and rapid identification of native and transplant ureters. In addition, side-to-side anastomosis of transplant-to-native ureters allows for preservation of ureteral vasculature. In this limited series, the SP robotic platform demonstrates great promise in simplifying and streamlining our approach to ureteral strictures in this patient population.


Body mass index associates with amyotrophic lateral sclerosis survival and metabolomic profiles.
Body mass index (BMI) is linked to amyotrophic lateral sclerosis (ALS) risk and prognosis, but additional research is needed. The aim of this study was to identify whether and when historical changes in BMI occurred in ALS participants, how these longer term trajectories associated with survival, and whether metabolomic profiles provided insight into potential mechanisms. ALS and control participants self-reported body height and weight 10 (reference) and 5 years earlier, and at study entry (diagnosis for ALS participants). Generalized estimating equations evaluated differences in BMI trajectories between cases and controls. ALS survival was evaluated by BMI trajectory group using accelerated failure time models. BMI trajectories and survival associations were explored using published metabolomic profiling and correlation networks. Ten-year BMI trends differed between ALS and controls, with BMI loss in the 5 years before diagnosis despite BMI gains 10 to 5 years beforehand in both groups. An overall 10-year drop in BMI associated with a 27.1% decrease in ALS survival (P = .010). Metabolomic networks in ALS participants showed dysregulation in sphingomyelin, bile acid, and plasmalogen subpathways. ALS participants lost weight in the 5-year period before enrollment. BMI trajectories had three distinct groups and the group with significant weight loss in the past 10 years had the worst survival. Participants with a high BMI and increase in weight in the 10 years before symptom onset also had shorter survival. Certain metabolomics profiles were associated with the BMI trajectories. Replicating these findings in prospective cohorts is warranted.


Characterization and functional analysis of an α-adrenergic-like octopamine receptor in the small brown planthopper Laodelphax striatellus.
As an important biogenic amine in invertebrates and corresponding to the neurotransmitter norepinephrine in vertebrates, octopamine (OA) regulates diverse physiological and behavioral processes by binding to specific octopamine receptors (OARs) in invertebrates. At present, OARs have been identified and characterized in several insects. However, less is known about the OARs of Laodelphax striatellus, one of the most destructive pests in East Asian rice fields. In the present study, an α1-adrenergic-like OAR (LsOA1) from L. striatellus was cloned. LsOA1 has the typical characteristics of G-protein coupled receptors and is clustered with other insect homologs. The transcript level of LsOA1 varied in various stages and tissues, and was highly expressed at the egg stage and in the brain. Silencing of LsOA1 causes a reduction in vitellogenin (LsVg) and vitellogenin receptor (LsVgR) expression. Although LsOA1 interference did not affect the fecundity and survival of L. striatellus, the hatching rate of L. striatellus was significantly reduced, and the hatching period was prolonged. The decrease in the amount of honeydew excreted after silencing LsOA1 indicates that LsOA1 may be involved in regulating the feeding behavior of L. striatellus. In addition, the interference of LsOA1 significantly reduced the expression of capsid protein (CP) and viral RNA3 segment (RNA3) in rice stripe virus (RSV)-viruliferous L. striatellus, but did not affect the vertical transmission rate of RSV. The present study demonstrated that LsOA1 played a crucial role in the physiological and behavioral processes of L. striatellus, which will provide the basis for developing a new target gene for pest control.


A private strain-specific idiotype-like structure discovered on CBA-anti-C57BL/6 T lymphocytes.
Using rabbit anti-CBA-anti-C57BL/6 sera, a private strain-specific idiotype-like determinant(s) was detected by cellular radioimmunoassay on activated CBA-anti-C57BL/6 T cells. This structure was not expressed on other activated T lymphocytes: CBA-anti-BALB/c; C3H-anti-C57BL/6; AKR-anti-C57BL/6; A/Sn-anti-C57BL/6; BALB/c- anti-C57BL/6; DBA/2-anti-C57BL/6. It is suggested that the gene(s) coding for the private strain-specific idiotype-like determinant(s) of T-cell antigen-recognizing receptors is not located within the murine H-2 complex.


Hypervalent Iodine-Mediated Intramolecular trans-Aminocarboxylation and Oxoaminocarboxylation of Alkynes: Divergent Cascade Annulations of Isocoumarins under Metal-Free Conditions.
An exclusive trans-aminocarboxylation and oxoaminocarboxylation of diarylalkynes were realized through hypervalent iodine-mediated cascade annulations under metal-free conditions, leading to divergent assembly of fused or spiro polycyclic heterocycles with a dosage of the hypervalent iodine oxidant. The mechanisms for the formation of both products are proposed.


Pre-pregnancy risk assessment and counselling of the cardiac patient.
Pregnant women with heart disease often have an increased risk of maternal cardiovascular and offspring complications. The magnitude of these risks varies depending on the type and severity of the underlying disease. Therefore risk assessment should be performed before pregnancy. This can be accomplished by taking into account predictors and risk scores that have been developed in large populations of pregnant women with heart disease, as well as by consulting disease-specific pregnancy literature. A system that integrates all available knowledge about the risk of pregnancy is the adapted World Health Organisation risk classification. The safety of pregnancy for women with heart disease can be enhanced by adequate risk assessment and counselling.


Efficacy and safety of primary thromboprophylaxis for the prevention of venous thromboembolism in patients with cancer and a central venous catheter: A systematic review and meta-analysis.
Venous thromboembolism (VTE) is a leading cause of mortality in patients with cancer and is associated with significant morbidity and healthcare expenditure. The risk of VTE is increased following the insertion of a central venous catheter (CVC) for chemotherapy delivery and supportive care. The risks and benefits of primary thromboprophylaxis in patients with cancer and CVC are unclear. We sought to assess the rates of VTE and bleeding complications and to determine the efficacy and safety of primary thromboprophylaxis in adult patients with cancer and a CVC. A systematic search of MEDLINE, EMBASE, and all EBM was conducted. Randomized controlled trials (RCTs) of adult patients with cancer and a CVC receiving primary thromboprophylaxis compared to observation/placebo were included. The primary efficacy and safety outcomes were total VTE and major bleeding episodes, respectively. A total of 12 RCTs (3545 patients) were included in the analysis. The total rates of VTE were significantly lower in patients receiving thromboprophylaxis compared to those not receiving primary prevention (7.6% vs. 13%; Odds Ratio (OR) 0.51, 95% CI 0.32-0.82, p < 0.01). The rates of major bleeding complications were not higher in patients receiving thromboprophylaxis (0.9% vs. 0.6%; OR 1.12, 95% CI 0.29-4.40, p = 0.87). Primary thromboprophylaxis significantly reduced the risk of VTE without increasing the risk of major bleeding complications in patients with cancer and CVC. Future studies are needed to confirm these findings.