Stoichiometry of Rtt109 complexes with Vps75 and histones H3-H4.
Histone acetylation is one of many posttranslational modifications that affect nucleosome accessibility. Vps75 is a histone chaperone that stimulates Rtt109 acetyltransferase activity toward histones H3-H4 in yeast. In this study, we use sedimentation velocity and light scattering to characterize various Vps75-Rtt109 complexes, both with and without H3-H4. These complexes were previously ill-defined because of protein multivalency and oligomerization. We determine both relative and absolute stoichiometry and define the most pertinent and homogeneous complexes. We show that the Vps75 dimer contains two unequal binding sites for Rtt109, with the weaker binding site being dispensable for H3-H4 acetylation. We further show that the Vps75-Rtt109-(H3-H4) complex is in equilibrium between a 2:1:1 species and a 4:2:2 species. Using a dimerization mutant of H3, we show that this equilibrium is mediated by the four-helix bundle between the two copies of H3. We optimize the purity, yield, and homogeneity of Vps75-Rtt109 complexes and determine optimal conditions for solubility when H3-H4 is added. Our comprehensive biochemical and biophysical approach ultimately defines the large-scale preparation of Vps75-Rtt109-(H3-H4) complexes with precise stoichiometry. This is an essential prerequisite for ongoing high-resolution structural and functional analysis of this important multi-subunit complex.


Effect of calcitonin treatment on deafness due to Paget's disease of bone.
Seventeen patients with Paget's disease of the skull and deafness were followed for nine to 18 months. Patients who received calcitonin treatment showed less deterioration in hearing than untreated patients. Calcitonin treatment may retard the progression of deafness in Paget's disease, and further studies are indicated.


A developmental study on the effect of stimulus rate on the auditory evoked brain-stem response.
Four groups of subjects were presented auditory stimuli differing only in repetition rate. One group was adults, another term newborns, and the other 2 groups were preterm newborns tested at respectively, 32 and 36 weeks postconceptional age. All 4 groups were judged to be audiologically and neurologically normal at the time of testing. Six stimulus repetition rates were presented to each subject, 10, 20, 40, 50, 66 2/3, and 80/sec. Auditory evoked brain-stem responses (ABRs) were recorded to each stimulus. Increasing repetition rate increased ABR wave form latencies and decreased ABR wave form amplitudes at all ages tested. For the most reliable measurement, wave V latency, a linear function effectively described the latency-rate function for individual subjects at all ages. The slope of the wave V latency-rate function increased with decreasing age. It was 300 microseconds decade change in rate at 32 weeks, 227 microseconds/decade at 36 weeks, 162 microseconds/decade at term, and 86 microseconds/decade in adults. Wave V latencies were more prolonged by rate than waves I and III and the differences in the rate effects between waves V and I and III increased with decreasing age. Amplitude was a less reliable measurement and amplitude-rate effects were less consistent than latency-rate effects.


Recent developments in pharmaceutical salts: FDA approvals from 2015 to 2019.
Around half of the new molecular entities approved by the US Food and Drug Administration (FDA) are pharmaceutical salts. The pharmaceutical salts have been on a continuous growth trajectory since the approval of the first salt form in 1939. This review aims to provide updates on pharmaceutical salts approved by the FDA between 2015 and 2019. The five-year drug-approval database contains 61 pharmaceutical salts, featuring a diverse range of counterions; however, hydrochlorides are the most abundant. The chemical structures of all pharmaceutical salts in each class are presented here, along with their therapeutic indications and date of approval. The reason behind the selection of a particular counterion and the technical superiority achieved by the salt form over the free active pharmaceutical ingredient base are also discussed.


Radiolabeling, Quality Control, and Cell Binding Studies of New 99mTc-Labeled Bisphosphonates: 99mTc-Ibandronate Sodium.
Early detection of bone cancer is critical for treating symptoms, minimizing pain, and increasing overall quality of life. It is critical to develop novel radiopharmaceuticals with high labeling efficiency and stability for the diagnosis of bone cancer. This research aims to design a novel radiopharmaceutical that may be used to diagnose bone cancer. In this study, ibandronate sodium (IBD), a bisphosphonate analog, was radiolabeled with technetium-99m [99mTc] and quality control tests on the newly developed radiopharmaceutical ([99mTc]Tc-IBD) were performed using radioactive thin layer chromatography. After that, the incorporation of [99mTc]Tc-IBD into hydroxyapatite (HA) crystals and a human bone osteosarcoma cell line (U2OS) was tested. According to the results obtained, optimal radiolabeling procedure was obtained for [99mTc]Tc-IBD with 200 μg.mL-1 IBD, 20 μg stannous chloride, and 99mTc with 37 MBq radioactivity. The reaction mixture was adjusted to pH 5.5 and incubated at room temperature for 15 min. The radiochemical purity of [99mTc]Tc-IBD was found to be greater than 95% at room temperature for up to 6 h. Additionally, chromatography analysis showed >95% [99mTc]Tc-IBD complex formation with promising stability for up to 24 h in saline and up to 2 h in cell medium. The percentage binding of IBD to HA was 83.70 ± 3.67 and the logP of [99mTc]Tc-IBD was -1.1014. The radiolabeled complex exhibited a higher rate of cell incorporation to U2OS cells compared to Reduced/Hydrolyzed 99mTcO4 -. The newly produced radiopharmaceutical is very promising according to the results of in vitro cell culture, HA binding, and quality studies, and will be a step forward for further studies in nuclear medicine for bone cancer diagnostics.


Interference effects in transient Kerr spectra of a semiconductor multilayer structure.
We experimentally study the spectra of the transient Faraday and Kerr effects near exciton resonances of a GaAs multiple quantum well. A multilayer calculation with a transfer matrix model accounts quantitatively for the linear transmission (reflectivity) spectra and the Faraday (Kerr) spectra. The Faraday and Kerr spectra do not obey a Kramers-Kronig relation. This phenomenon was found to be due to the multiple reflection effects on the Kerr spectra.


The use of parenteral nutrition in calves.
Parenteral nutrition has been an important adjunct to therapy of abdominal diseases in calves, with chronic diarrhea and wasting being the most common indication. Parenteral nutrition is administered on a short-term basis to prevent further protein-energy malnutrition in debilitated calves that cannot or will not consume adequate quantities of milk. Parenteral nutrition solutions consist of a protein source (amino acids) and energy sources (glucose and lipid emulsions), supplemented as needed with balanced electrolytes and vitamins. Complications due to PPN are rare, and it is the authors' clinical impression that survivability is enhanced when PPN is employed, although enhanced survivability was not demonstrated in one controlled experimental trial.


Pleural recurrence after surgery for pleomorphic adenoma arising from peripheral lung: computed tomography-guided percutaneous needle biopsy as a possible mechanism of local failure.
A 75-year-old male was referred to our hospital because of an abnormal shadow found in the right lung 2 years prior that had been increasing in size. Chest computed tomography showed a 1-cm well-defined nodule in the periphery of the right middle lobe. Although a computed tomography-guided percutaneous needle biopsy was performed, the results were indeterminate. In observations over the course of 1 year, the tumor size increased. Surgical resection was finally performed for diagnosis and treatment, and histological findings revealed a pulmonary pleomorphic adenoma. 2 years after surgery, pleural dissemination unfortunately developed. We present here a case of recurrence as pleural dissemination despite complete resection of a pulmonary pleomorphic adenoma arising from peripheral lung tissue. There is a possibility that the local failure is related to percutaneous needle biopsy.


The probability of interspecific competitive situations in scale-insects (Homoptera, Coccoidae) : Interspecific competition of scale-insects.
A large scale survey, covering some 25 million km2 of Eastern-Europe, provided distributional data, and a more detailed picture on factors determining species composition and abundance of scale-insects colonizing deciduous orchard trees. No interspecific competition or competitive situations were detected among the 21 scale insect species, when taking into consideration the whole geographic area surveyed. Of all cases, 3.2% showed significant spatial separation in smaller geographic regions. However, no evidence for competition was found between species with overlapping distributions. In the case of introduced species, the role of past competition can also be excluded. Separation was thought to be determined by differences in ecological requirements. There is some probability of competition in the "transitional zone" (significant separation in 0.8% of cases), and somewhat more (2.4%) in the "Southern zone". There was potential competition between species classified as "Mediterranean" and "invader" subguilds (7.1% of frequent species pairs), as well as between the "Southern" and "invader" (2.4% of frequent species pairs) subguilds. Its probability was very low between the species of the "endemic" (0.8% of frequent species pairs) and "invader" (1.6% of frequent species pairs) subguilds.


Contribution of bacterial-fungal balance to plant and animal health.
Surfaces of plants and animals are colonized by complex multi-kingdom microbial communities that comprise prokaryotic (i.e. archaea, bacteria) and eukaryotic (i.e. fungi, protists) microbes. Composition and variation in these multi-kingdom microbial communities are influenced by host and environmental cues that drive microbial community differentiation between host niches. Recent evidence indicates that, beyond these major forces, interactions between microbiota members also contribute to the establishment, the stability, and the resilience of host-associated microbial communities. Particularly, the interplay between bacteria and fungi in host niches appears critical for community functionality and alteration of the balance between these microbes emerges as a potential cause of disease. Here, we discuss the extent to which interactions between these microbes drive variation in community composition across plant and animal niches and we provide examples illustrating that altering bacterial-fungal balance in the microbiome can lead to disease.


Neural correlates of blink suppression and the buildup of a natural bodily urge.
Neuroimaging studies have elucidated some of the underlying physiology of spontaneous and voluntary eye blinking; however, the neural networks involved in eye blink suppression remain poorly understood. Here we investigated blink suppression by analyzing fMRI data in a block design and event-related manner, and employed a novel hypothetical time-varying neural response model to detect brain activations associated with the buildup of urge. Blinks were found to activate visual cortices while our block design analysis revealed activations limited to the middle occipital gyri and deactivations in medial occipital, posterior cingulate and precuneus areas. Our model for urge, however, revealed a widespread network of activations including right greater than left insular cortex, right ventrolateral prefrontal cortex, middle cingulate cortex, and bilateral temporo-parietal cortices, primary and secondary face motor regions, and visual cortices. Subsequent inspection of BOLD time-series in an extensive ROI analysis showed that activity in the bilateral insular cortex, right ventrolateral prefrontal cortex, and bilateral STG and MTG showed strong correlations with our hypothetical model for urge suggesting these areas play a prominent role in the buildup of urge. The involvement of the insular cortex in particular, along with its function in interoceptive processing, helps support a key role for this structure in the buildup of urge during blink suppression. The right ventrolateral prefrontal cortex findings in conjunction with its known involvement in inhibitory control suggest a role for this structure in maintaining volitional suppression of an increasing sense of urge. The consistency of our urge model findings with prior studies investigating the suppression of blinking and other bodily urges, thoughts, and behaviors suggests that a similar investigative approach may have utility in fMRI studies of disorders associated with abnormal urge suppression such as Tourette syndrome and obsessive-compulsive disorder.


Kinetic dielectric decrements and conducting liquids.
We have calculated influence of ion migration on the measured dielectric constant of an electrolyte solution. The solvent is assumed to be a viscous, incompressible, polarizable liquid continuum having a finite dielectric relaxation time, while the ion is a rigid, impenetrable body. The decrement in the static permitivity of the solution with respect to the pure solvent is shown to be proportional to the product of solvent dielectric relaxation time and conductivity of the solution, with an additional contribution arising from viscous relaxation in the solvent.


Morbidity and mortality following noncardiac surgical procedures among children with autosomal trisomy.
Trisomy 13 (T13), trisomy 18 (T18), and trisomy 21 (T21) are the most common autosomal trisomies. One unifying feature of all trisomies is their association with major congenital malformations, which often require life-prolonging surgical procedures. Few studies, mostly among cardiac surgery patients, have examined the outcome of those who undergo surgical procedures. We examined the differences in postsurgical outcomes between the trisomy groups. Using the National Surgical Quality Improvement Program dataset, we identified children (<18 years of age) with T13, T18, or T21 who underwent noncardiac surgery (2012-2018). We estimated the incidence of mortality and indicator of resource utilization (unplanned reoperation, unplanned tracheal reintubation, and extended length of hospital stay). Of the 349 158 inpatient surgical cases during the study period, we identified 4202 children with one of the autosomal trisomies of interest (T13: 152; T18: 335; and T21: 3715). The rates of postoperative mortality were substantially higher for T18 and T13 than T21 and nontrisomy children (T18 vs. T21: 11.1% vs. 1.6%, adjusted odds ratio: 5.01, 95%CI: 2.89,8.70, p < .01), (T13 vs. T21: 8.1% vs. 1.6%, adjusted odds ratio: 2.86, 95%CI: 1.25,6.54, p = .01). Children with T18 had the highest rates of extended length of stay (62.7%) and prolonged mechanical ventilation (32.5%). T18 and T13 neonates had the highest surgical mortality burden (T13: 26.5%, T18: 31.8%, and T21: 2.8%). Approximately, one-third of T18 and T13 neonates, who had surgery, died, underscoring the lethality of these trisomies and the need for a comprehensive preoperative ethical discussion with families of these children.


ESTER: an expert system for management of respiratory weaning therapy.
The withdrawal of mechanical ventilation generally presents no problems if carried out when the values of certain predictive physiological variables suggest that the patient will be able to breathe for him or herself. In certain cases, however, a more gradual weaning procedure is necessary, in which the amount of mechanical assistance provided is in some way reduced little by little. One of the usual means of achieving this gradual reduction is by intermittent mandatory ventilation (IMV), in which short bursts of mechanical ventilation are separated by progressively longer periods of "ventilator silence" which stimulate the patient's endogenous respiration. ESTER is an expert system in which the most widely accepted criteria are systematically called upon to supply advice to the clinician who has to prescribe a respiratory therapy regime suited to the needs of the patient. After effecting a preliminary prognosis of the patient's condition, ESTER asks for certain physiological parameters to be keyed in. Analysis of these parameters reveals the patient's condition and allows a recommended respiratory therapy to be designed.


Prognostic significance of pretreatment variables in patients with invasive cervical cancer.
In 119 consecutive patients with invasive cervical cancer 92 variables of potential significance in predicting recurrence were determined before treatment. In 49 patients recurrent disease was diagnosed during follow-up after therapy. The investigated variables include: clinical data, routinely performed hematological and biochemical tests, histopathological data, oncofetal antigens, placental and pregnancy associated substances, serum levels of acute phase reactants, complement components, immunoglobulins and circulating immune complexes, and assays measuring the general immune competence of the patient. Thirty-three of the variables appeared to give statistically significant differences between values of future recurrence and non-recurrence patients. Further selection was carried out by stepwise forward discriminant analysis. This selection resulted in a prognosis rule using a subset of 7 variables. Carcino-embryonic antigen and the complement component C3PA appeared to be the most powerful variables. Although the stage of disease was the third most important single variable, it did not add prognostic information, once CEA and C3PA were used. By applying the prognosis rule a probabilistic prediction is obtained for each patient. In about 60% of the future recurrences and 40% of the future non-recurrence patients, these predictions reached a high level of accuracy. It was argued that the prediction of non-recurrence does not warrant to change the treatment protocol at present. Whether the prediction of recurrence is clinically useful remains to be clarified.


The Effectiveness of 2% Lidocaine Gel Compared to 0.5% Tetracaine Eye Drop As Topical Anesthetic Agent for Phacoemulsification Surgery.
Topical anesthetics have become the primary choice in phacoemulsification procedures for cataract extraction. The most common topical anesthetic drug used is 0.5% tetracaine eye drops. Repeated administration of 0.5% tetracaine drops can cause corneal epithelial damage. Two percent lidocaine gel is latest option which has longer contact time with corneal epithelium. To compare the effectiveness of 2% lidocaine gel with 0.5% tetracaine drops in phacoemulsification surgery. The study was a single blinded randomized clinical trial from March to July 2017 in patients underwent phacoemulsification cataract surgery. There were 72 subjects with age ≥ 40 years old who received randomization and divided into 2 groups: 2% lidocaine gel group and 0.5% tetracaine eye drop group. Topical anesthetics were applied 5 minutes before surgery. Five minutes after surgery, pain scale perceived during surgery was assessed by using a numerical rating scale. At the end of surgery, the subject filled the satisfaction questionnaire on topical anesthetic drugs administered. The ophthalmologists were also given a satisfactory questionnaire for topical anesthetic drugs selected for the procedure. The median pain scale for 2% lidocaine gel group pain scale was 1; meanwhile, the median pain scale for 0.5% tetracaine eye drops was 3 (P < 0.05). Two percent lidocaine gel was more effective in relieving pain during phacoemulsification cataract surgery compared with 0.5% tetracaine drops.


N-(4,6-Dimeth-oxy-pyrimidin-2-yl)-2-(3-methyl-phen-yl)acetamide.
In the title compound, C(15)H(17)N(3)O(3), the dihedral angle between the pyrimidine and benzene rings is 87.0 (7)°. In the crystal, mol-ecules are linked into inversion dimers with R(2) (2)(8) graph-set motifs by a pair of N-H⋯O hydrogen bonds. Weak C-H⋯O hydrogen bonds and inter-molecular π-π inter-actions [centroid-centroid distance = 3.544 (1) Å] are also observed.


Comparison of clonidine and epinephrine in lidocaine anaesthesia for lower third molar surgery.
The admixture of clonidine or epinephrine to lidocaine for inferior alveolar nerve block was studied with regard to onset, duration, intensity of anaesthesia, postoperative analgesia, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), ST segment depression > or =1 mm and cardiac arrhythmias. Forty healthy patients (ASA I) received 2 ml 2% lidocaine with clonidine (15 microg/ml; n = 20) or epinephrine (12.5 microg/ml; n = 20) in a double-blind fashion for lower third molar surgery. Duration and intensity were not different between groups, while onset was significantly different by subjective evaluation. The need for postoperative pain medication was significantly lower in the clonidine group. There was a significant decrease in SBP and MAP in both groups 35 min after administration of anaesthesia compared with basal values, while DBP was significantly lower only in the clonidine group. There was no significant difference in SBP, DBP and MAP between groups. HR was significantly increased in the epinephrine group 5 min after administration of anaesthesia and during surgery compared with the clonidine group and with basal values. The presented data suggest that clonidine could be a useful and safe alternative to epinephrine for intraoral block anaesthesia.


The Gift Relationship: Discovering Gift Exchange in Interpersonal Practice.
Encountering the deeper flows of human experience and glimpsing the touch of the divine on the human soul offer guides and companions rich reflective content for their ongoing formation. This is a precious gift which pilgrims constantly place before their companions, though at times it remains 'unwrapped'. Through offering a supervision narrative, this paper provides a phenomenological description of such a gift exchange.


Accuracy enhancement in the estimation of molecular hydration free energies by implementing the intramolecular hydrogen bond effects.
The formation of intramolecular hydrogen bonds (IHBs) may induce the remarkable changes in molecular physicochemical properties. Within the framework of the extended solvent-contact model, we investigate the effect of implementing the IHB interactions on the accuracy in estimating the molecular hydration free energies. The performances of hydration free energy functions including and excluding the IHB parameters are compared using the molecules distributed for SAMPL4 blind prediction challenge and those in Free Solvation Database (FSD). The calculated hydration free energies with IHB effects are found to be in considerably better agreement with the experimental data than those without them. For example, the root mean square error of the estimation decreases from 2.56 to 1.66 and from 1.73 to 1.54 kcal/mol for SAMPL4 and FSD molecules, respectively, due to the extension of atomic parameter space to cope with IHBs. These improvements are made possible by reducing the overestimation of attractive interactions between water and the solute molecules involving IHBs. The modified hydration free energy function is thus anticipated to be useful for estimating the desolvation cost for various organic molecules.


Whole Genome Amplification by Isothermal Multiple Strand Displacement Using Phi29 DNA Polymerase.
The here described method of isothermal whole genome amplification (iWGA) uses a Phi29 DNA polymerase-based kit (Illustra GenomiPhi V2 DNA Amplification Kit) that amplifies minute quantities of DNA by multiple strand displacement upon random hexamer primer binding. Starting from genomic DNA or single cells this amplification yields up to 5 μg of iWGA product with fragment lengths of 10 kb and longer. As this amplification lacks the need of fragmenting DNA, its products are well suited for many downstream applications (e.g. sequencing and DNA profiling). On the contrary, degraded DNA samples are not supported by the nature of the amplification and are not well suited.


Mechanisms of islet amyloidosis toxicity in type 2 diabetes.
Amyloid formation by the neuropancreatic hormone, islet amyloid polypeptide (IAPP or amylin), one of the most amyloidogenic sequences known, leads to islet amyloidosis in type 2 diabetes and to islet transplant failure. Under normal conditions, IAPP plays a role in the maintenance of energy homeostasis by regulating several metabolic parameters, such as satiety, blood glucose levels, adiposity and body weight. The mechanisms of IAPP amyloid formation, the nature of IAPP toxic species and the cellular pathways that lead to pancreatic β-cell toxicity are not well characterized. Several mechanisms of toxicity, including receptor and non-receptor-mediated events, have been proposed. Analogs of IAPP have been approved for the treatment of diabetes and are under investigation for the treatment of obesity.


Design, synthesis and anticancer evaluation of selective 2,4-disubstituted pyrimidine CDK9 inhibitors.
Specific inhibition on CDK9 has been proven to be a promising targeted cancer therapy. In this work, fourteen novel 2,4-disubstituted pyrimidine derivatives were designed and synthesized as potent and selective CDK9 inhibitors. These compounds showed broad anti-proliferative activities in various tumor cell lines, especially for PANC-1 cells with IC50 values as low as 0.08 μM. The most selective compound 8d was 84-fold selective for CDK9 over CDK2. Mechanism study indicated that 8d induced apoptosis of PANC-1 cells and arrested the cell cycle at G2/M phase in a dose-dependent manner. Decreased phosphorylation of the CTD of RNAPII at Ser-2 and downregulation of CDK9 were confirmed in PANC-1 cells. Besides, Molecular docking was also performed to gain insights into the ligand-binding interactions of 8d inside CDK9 and CDK2 binding sites. In vivo studies indicated that 8d exhibited potent anti-tumor effects in PANC-1 xenograft models without causing obvious loss of body weight. Our research suggests that compound 8d, as a potent CDK9 inhibitor, can be considered as a good lead-candidate for further development.


Epigenetics in myeloid malignancies.
Myeloid hematological malignancies are among the epigenetically best characterized neoplasms. The comparatively low number of recurring balanced and unbalanced chromosomal abnormalities as well as common genetic mutations has enabled scientists to relate epigenetic states to these. The ease of accessing malignant cells through bone marrow aspiration has certainly contributed to the fast expansion of knowledge. Even so, the clinical and pathogenetic relevance of epigenetic changes is still not known, and the field will certainly evolve very fast with the development of new analytic techniques. The first example of successful epigenetic therapy is seen in myeloid malignancies, in the high-risk myelodysplastic syndromes (MDS) which are routinely treated with the demethylating agent azacytidine.This chapter will concentrate on describing the epigenetic changes in acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and MDS. An overview of clinical relevance and epigenetic therapeutic approaches is also made.


Short- and long-term efficacy of aspirin and clopidogrel for thromboprophylaxis for mechanical heart valves: an in vivo study in swine.
In the interest of exploring alternatives to warfarin, we tested the hypothesis that clopidogrel combined with aspirin is effective for thromboprophylaxis of mechanical valves using a swine model. Adult swine underwent heterotopic implantation of a modified bileaflet mechanical valved conduit bypassing the ligated, native descending thoracic aorta. Animals were randomized to no anticoagulation (n = 7), 175 U/kg dalteparin administered subcutaneously twice daily (n = 9), 325 mg of aspirin (n = 6), 75 mg of clopidogrel (n = 6), or 325 mg of aspirin and 75 mg of clopidogrel daily (n = 6) and survived for 30 days. Additionally, 11 animals were randomized to no anticoagulation (n = 5) or 325 mg of oral aspirin and 75 mg of clopidogrel daily (n = 6) and survived for 150 days. At 30 days, we observed 216 +/- 270 mg of thrombus for the no anticoagulation group, 53 +/- 91 mg for the dalteparin group, 33 +/- 23 mg for the aspirin group, 25 +/- 10 mg for the clopidogrel group, and 17 +/- 9 mg for the combined aspirin and clopidogrel group, respectively (P < .01 for clopidogrel and aspirin vs no anticoagulation). At 150 days, we observed 223 +/- 200 mg of thrombus for the no anticoagulation group and 4 +/- 4 mg for the aspirin and clopidogrel group (P = .02). Mean platelet deposition on the valve was 4.1 x 10(9) +/- 3.6 x 10(9) for the no anticoagulation and 6.81 x 10(7) +/- 1.4 x 10(8) for the combined aspirin and clopidogrel groups, respectively (P = .03). No major hemorrhagic events were observed. Effective short- and long-term thromboprophylaxis of mechanical valves can be achieved by using dual-antiplatelet therapy in this porcine model. Prospective human trials should be conducted with combination aspirin and clopidogrel as an alternative to warfarin in patients with bileaflet mechanical aortic valves.


Epitope Mapping Using the Cell-Based 2 × Alanine Substitution Method About the Anti-mouse CXCR6 Monoclonal Antibody, Cx6Mab-1.
An anti-mouse CXC chemokine receptor 6 (mCXCR6) monoclonal antibody (mAb), Cx6Mab-1, was developed recently. Cx6Mab-1 is applicable for flow cytometry, Western blotting, and enzyme-linked immunosorbent assay. The purpose of this study is to determine the binding epitope of Cx6Mab-1 using 2 × alanine mutated mCXCR6. Analysis of flow cytometry revealed that Cx6Mab-1 did not recognize S8A-A9G, L10A-Y11A, D12A-G13A, and H14A-Y15A mutants of mCXCR6. The results clearly indicate that the binding epitope of Cx6Mab-1 includes Ser8, Ala9, Leu10, Tyr11, Asp12, Gly13, His14, and Tyr15 of mCXCR6. The successful determination of the Cx6Mab-1 epitope might contribute to the pathophysiological investigation of mCXCR6.


Systolic pressure slope: system for automated display and calculation.
The rate of rise of arterial blood pressure--the systolic pressure slope--has been measured noninvasively at the ankle and has been shown to be reduced by minor degrees of peripheral arterial stenosis. This report describes an electronic system used to display the systolic part of the arterial pressure wave. The system uses noninvasive data from an ECG, a blood pressure cuff, and a Doppler ultrasound detector. From these data the systolic pressure slope is measured automatically. One hundred and sixty-eight recordings from the limbs of 10 normal subjects were analyzed in detail and confirmed the reproducibility of the system. The points used to calculate the systolic slope fell close to a straight line, with correlation coefficients averaging 0.96. An average of eight repeat measurements were made per limb, and the coefficients of variation averaged 6.5%. Mean values for the normalized systolic pressure slope agreed with previously published data.


Structure revision of circumdatins A and B, benzodiazepine alkaloids produced by marine fungus Aspergillus ostianus, by X-ray crystallography.
The structures of circumdatins A and B, pentacyclic alkaloids produced by Aspergillus ostianus, were revised from the previously reported betaine structures to unique oxepin ones by X-ray crystallography. The co-occurring known alkaloids, circumdatins D, E, and H, and a new compound reported here, circumdatin J, have a common framework.


What's in a name? Considerations of homologies and nomenclature for vertebrate social behavior networks.
Behavioral neuroendocrinology is an integrative discipline that spans a wide range of taxa and neural systems, and thus the appropriate designation of homology (sameness) across taxa is critical for clear communication and extrapolation of findings from one taxon to another. In the present review we address issues of homology that relate to neural circuits of social behavior and associated systems that mediate reward and aversion. We first address a variety of issues related to the so-called "social behavior network" (SBN), including homologies that are only partial (e.g., whereas the preoptic area of fish and amphibians contains the major vasopressin-oxytocin cell groups, these populations lie in the hypothalamus of other vertebrates). We also discuss recent evidence that clarifies anterior hypothalamus and periaqueductal gray homologies in birds. Finally, we discuss an expanded network model, the "social decision-making network" (SDM) which includes the mesolimbic dopamine system and other structures that provide an interface between the mesolimbic system and the SBN. This expanded model is strongly supported in mammals, based on a wide variety of evidence. However, it is not yet clear how readily the SDM can be applied as a pan-vertebrate model, given insufficient data on numerous proposed homologies and a lack of social behavior data for SDM components (beyond the SBN nodes) for amphibians, reptiles or fish. Functions of SDM components are also poorly known for birds. Nonetheless, we contend that the SDM model provides a very sound and important framework for the testing of many hypotheses in nonmammalian vertebrates.


Consumption of home-prepared meal at workplace as a predictor of glycated haemoglobin among people with type 2 diabetes in Hong Kong: a mixed-methods study.
There is increasing attention on association between eating patterns and diabetes control following global changes in eating patterns. There had been very limited research on the eating patterns of diabetic patients with employment, although working age population has seen the highest increase in diabetes incidence. This study aimed to identify workplace eating patterns in relation to glycaemic control among type 2 diabetic patients with employment. This is a sequential mixed-methods study. The exploratory qualitative study involved focus group interviews with 31 type 2 diabetic patients with employment, which guided the design of a subsequent cross-sectional investigation involving 185 patients with employment. Thematic analysis was conducted on the qualitative data to identify workplace eating patterns most relevant to glycaemic control. Hierarchical multiple linear regression was performed to examine association between workplace eating pattern and glycaemic control, proxied by HbA1c. The focus group interviews identified frequency in the consumption of home-prepared meals (HPM) and meal hours as the major workplace eating patterns that affected glycaemic control. The cross-sectional study confirmed that regular consumption of HPM at workplace could explain variance of HbA1c, independent of socio-demographic factors, lifestyle factors and disease condition, with R2 = 0.146, F(14, 170) = 2.075, p = 0.015; adjusted R2 = 0.076. Patients who were female, in non-skilled occupation, on shift, with fixed work location and had break during work were more likely to consume HPM. Consumption of HPM at workplace should be promoted to facilitate better glycaemic control by type 2 diabetic patients with employment, possibly through more practical dietary advice, and workplace accommodation in terms of space and facilities. In the context of COVID-19 pandemic, consumption of HPM also meant additional protection for diabetic patients through reducing close contact exposures in restaurants.


Perceived danger associated with a property modulates cross category generalization.
Identifying projectable predicates is a key issue in understanding inductive inference. It is proposed that looking into the evolutionary psychology literature for adaptive properties may be one useful approach. One hypothesis that emerges from this literature is that properties that signal danger or harm should be more salient than properties that do not. Two studies are carried out to test this hypothesis. In study 1 participants were presented with a scenario involving the discovery of novel animals, for which there was incomplete information. Three types of properties (a harmful property, a neutral property, a beneficial property) were associated with animals in one (base) category and participants were asked to indicate strength of generalization of the property to a target within the category, and to a target across to another category. In the second experiment, the procedure was repeated, but in addition, subjects were also explicitly asked to indicate whether the base and target belonged to the same or different categories. Study 1 showed that the harmful property was more projectable compared to the beneficial and neutral properties. Study 2 reconfirmed this and further showed that it also promoted excessive generalization across categories. The results suggest that examination of adaptations identified by evolutionary psychologists may be a useful source of insight in the study of inductive inference. The online version contains supplementary material available at 10.1007/s11571-022-09793-3.


Polyphenol metabolism in differently colored cultivars of red currant (Ribes rubrum L.) through fruit ripening.
Rare red currants colors caused by low anthocyanin content in the pink and a lack of anthocyanins in the white cultivar correlated with low ANS gene expression, enzyme activity, and increased sugar/acid ratios. Changes in the contents of polyphenols, sugars, and organic acids in berries of the three differently colored Ribes rubrum L. cultivars ('Jonkheer van Tets', 'Pink Champagne', and 'Zitavia') were determined by LC-MS and HPLC at 4 sampling times during the last month of fruit ripening. The activities of the main flavonoid enzymes, chalcone synthase/chalcone isomerase (CHS/CHI), flavanone 3-hydroxylase (FHT), and dihydroflavonol 4-reductase (DFR), and the expression of anthocyanidin synthase (ANS) were additionally measured. Despite many attempts, activities of flavonol synthase and glycosyltransferase did not show reliable results, the reason of which they could not be demonstrated in this study. The pink fruited cultivar 'Pink Champagne' showed generally lower enzyme activity than the red cultivar 'Jonkheer van Tets'. The white cultivar 'Zitavia' showed very low CHS/CHI activity and ANS expression and no FHT and DFR activities were detected. The DFR of R. rubrum L. clearly preferred dihydromyricetin as substrate although no 3',4',5'-hydroxylated anthocyanins were present. The anthocyanin content of the red cultivar slightly increased during the last three weeks of ripening and reached a maximum of 890 mg kg-1 FW. Contrary to this, the pink cultivar showed low accumulation of anthocyanins; however, in the last three weeks of ripening, their content increased from 14 to 105 mg kg-1 FW. Simultaneously, the content of polyphenols slightly decreased in all 3 cultivars, while the sugar/acid ratio increased. The white cultivar had no anthocyanins, but the sugar/acid ratios were the highest. In the white and pink cultivars, reduction/lack of anthocyanins was mainly compensated by increased relative concentrations of hydroxycinnamic acids and flavonols.


Radiotherapy for locally advanced unresectable gallbladder cancer - A way forward: Comparative study of chemotherapy versus chemoradiotherapy.
For nonmetastatic locally advanced gallbladder cancer (LAGBC) which remains unresectable and nonmetastatic after chemotherapy, there is no consensus on whether to continue chemotherapy or add local radiotherapy (RT) for improving outcomes. Forty-five patients of surgically unresectable nonmetastatic LAGBC were analyzed. Twenty patients did not receive RT (no RT cohort) and received only chemotherapy, while 25 patients received RT (RT cohort) with conformal techniques along with concurrent gemcitabine-based chemotherapy. No RT and RT cohorts were compared for disease-related outcomes and toxicities. Median follow-up of the entire cohort was 11.5 months. Two-year progression-free survival (18.6% vs. 0%, P = 0.0001) and overall survival (37.3% vs. 5%, P = 0.0001) were significantly better in the RT cohort as compared to a no RT cohort. More number of patients had locoregional progression in the no RT cohort (85% vs. 32%, P = 0.0002). Radiation-induced acute and late gastrointestinal toxicity ≥ RTOG Grade 3 were seen in one and two patients, respectively. Addition of local RT to chemotherapy improves the survival outcomes and can be considered as a definite treatment modality for nonmetastatic LAGBC patients not amenable to surgery who have responded to chemotherapy.


Influence of personalised music and ice-tea options on post-operative well-being in the post anaesthesia care unit after general or regional anaesthesia. A pre-post-analysis by means of a questionnaire.
Assessment whether patients' wellbeing and disturbances in the post anaesthesia care unit could be influenced by the consecutive introduction of initially personalised music and then additionally various drink options. A pre-post-analysis by means of an anonymised survey with a validated questionnaire in a university hospital in central Europe. Wellbeing and disturbances in the post anaesthesia care unit. Patients' most frequently reported early postsurgical disturbances (n = 1335) were lack of wellbeing, dry mouth and pain in the surgical area. Reported rates of clinically relevant wellbeing were not statistically different in patients that were offered personalised music (46.5%) or additionally ice-tea (50.6%). No correlation could be found between wellbeing or physical discomfort and headphones or when ice-tea were offered. After a decade of increased efforts to improve patients' wellbeing in the postanaesthesia care unit we could not show further influence on it by the introduction of personalised music and ice-tea. We see the need for a more differentiated focus on this topic and the need for exploratory studies on patient perception. The most frequent claims were related to lack of wellbeing, pain in the surgical area and a dry mouth.


Partial deletion of the nicotinic cholinergic receptor alpha 4 or beta 2 subunit genes changes the acetylcholine sensitivity of receptor-mediated 86Rb+ efflux in cortex and thalamus and alters relative expression of alpha 4 and beta 2 subunits.
Alpha4 and beta2 nicotinic cholinergic receptor (nAChR) subunits can assemble in heterologous expression systems as pentameric receptors with different subunit stoichiometries that exhibit differential sensitivity to activation by acetylcholine, yielding biphasic concentration-effect curves. nAChR-mediated (86)Rb(+) efflux in mouse brain synaptosomes also displays biphasic acetylcholine (ACh) concentration-response curves. Both phases are mediated primarily by alpha4beta2(*)-nAChR, because deletion of either the alpha4 or beta2 subunit reduces response at least 90%. A relatively larger decrease in the component of (86)Rb(+) efflux with lower ACh sensitivity occurred with partial deletion of alpha4 (alpha4(+/-)), whereas a larger decrease in the component with higher ACh sensitivity was elicited by partial deletion of beta2 (beta2(+/-)). Immunoprecipitation with selective antibodies demonstrated that more than 70% of [(3)H]epibatidine binding sites in both regions contained only alpha4 and beta2 subunits. Subsequently, alpha4 and beta2 subunit content in the cortex and thalamus of alpha4 and beta2 wild types and heterozygotes was analyzed with Western blots. Partial deletion of alpha4 decreased and partial deletion of beta2 increased the relative proportion of the alpha4 subunit in assembled receptors. Although these methods do not allow exact identification of stoichiometry of the subtypes present in wild-type cortex and thalamus, they do demonstrate that cortical and thalamic nAChRs of the alpha4(+/-) and beta2(+/-) genotypes differ in relative expression of alpha4 and beta2 subunits a result that corresponds to the relative functional changes observed after partial gene deletion. These results strongly suggest that alpha4beta2-nAChR with different stoichiometry are expressed in native tissue.


Steps physicians report taking to reduce diversion of buprenorphine.
Physicians are challenged to effectively treat opioid dependent patients while minimizing diversion of potentially abusable medications, such as buprenorphine. The present study was designed to obtain information on steps physicians report taking to reduce diversion of buprenorphine. National quarterly surveys from 2008 to 2009 of qualified physicians who have prescribed buprenorphine were analyzed (N = 2,330). One part of the survey queried physicians about what steps they had taken to reduce abuse and diversion of buprenorphine from a pre-specified list of 12 steps. Other parts of the survey included questions on the physicians' training and experience. Physicians reported taking a mean of 4.4 steps. Longer experience prescribing buprenorphine, more buprenorphine-related educational training, and concern about diversion as a limitation on using buprenorphine for maintenance were associated with higher number of steps taken. Physicians are currently taking multiple steps to reduce diversion. Future research needs to verify if these steps are effective or are instead reducing access to treatment.


Relation of plasma leptin to C-reactive protein in older adults (from the Invecchiare nel Chianti study).
Obese subjects have higher circulating levels of C-reactive protein (CRP) than normal subjects, and it has been shown that CRP per se may contribute to atherogenesis. The mechanism linking increased fat mass with high CRP levels has not been exhaustively explained. It has been suggested that adipose tissue-produced cytokines, including interleukin-6, tumor necrosis factor-alpha, and interleukin-1beta, represent the causal link between increased body fat and high CRP levels. It has been hypothesized that the hormone leptin, released by fat cells, may stimulate CRP production independent of cytokines. This study measured circulating leptin, CRP, interleukin-6, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-8 in 946 community-dwelling older subjects (398 men, 548 women; age range 65 to 102 years) enrolled in a large population-based study. Confounders included demographics, functional, cognitive and affective status, diet and lifestyle, body composition, drugs, and chronic diseases. A direct association was found between leptin and CRP (p = 0.004), independent of cytokines and other possible confounders. The association was stronger in younger than in older subjects but was not influenced by gender or body mass index. In conclusion, these findings suggest that leptin may directly stimulate the production of CRP independent of fat-cell produced cytokines in older adults.


The mesenchyme expresses T cell receptor mRNAs: relevance to cell growth control.
The mesenchyme plays a crucial regulatory role in organ formation and maintenance. However, comprehensive molecular characterization of these cells is lacking. We found unexpectedly that primary mesenchyme, as well as mesenchymal cell clones, express T cell receptor (TCR)alphabeta mRNAs, lacking the variable region. Immunological and genetic evidence support the expression of a corresponding TCRbeta protein. Additionally, mRNAs encoding TCR complex components including CD3 and zeta chain are present. A relatively higher expression of the mesenchymal TCRbeta mRNA by cultured mesenchymal cell clones correlates with fast growth, whereas poorly expressing cells are slow growers and are contact inhibited. The clones that express relatively higher amount of the TCR mRNA exhibit an increased capacity to form tumors in nude mice. However, the expression of this mRNA in the mesenchyme is not per se leading to tumorigenesis, as demonstrated by primary mesenchyme that does not form tumors in mice while expressing moderate amounts of the TCR transcripts. The expression of mesencymal TCRbeta was confined to the G2/M phases of the cell cycle in the MBA-13 mesenchymal cell line. This cell cycle dependent expression, considered together with the correlation between growth properties and the level of TCR expression by cell clones, implies association of mesenchymal TCR with cell growth control.


Long-term follow-up of viable frozen aortic homografts. A viable homograft valve bank.
There is currently a renewed interest in the use of both fresh and commercially available frozen homograft valves for children and young adults. This has prompted us to review a series of 32 patients who received frozen homograft valves for aortic replacement between 1973 and 1975. The cryogenic technique evolved to include the use of selected antibiotics and equilibrated dimethyl sulfoxide solution to freeze homografts at a rate of 1 degrees C per minute to liquid nitrogen temperatures of -196 degrees C. Histologic sections of experimental frozen valves explanted 6 months postoperatively revealed the presence of viable donor cells, and tissue culture demonstrated the reproductive capacity of cusp fibroblasts. Of the 32 frozen viable homografts implanted in this series, 23 were inserted as free-sewn aortic replacements and nine were premounted on stents before implantation in the aortic position. There were two operative deaths, and three valves failed as a result of the technical problems of mounting in one patient and surgical insertion of a free graft in two patients. Of the 22 patients who remained at long-term risk, 13% with free-sewn grafts and 57% with premounted valves underwent reoperation for valve failure. After 10 years of follow-up, 15 (68%) of these patients, 12 (80%) with free-sewn and three (43%) with premounted valves, are alive with their original valve in place. Actuarial analysis shows that 58% of the 32 valves implanted are functional at the beginning of the eleventh year. There have been six late deaths resulting in an overall actuarial patient survival rate of 79% at 10 years and 69% after 13 years. These clinical results are believed to add support to our current application of the frozen homograft in selected patients.


Homogeneous trinder-coupled assay for the determination of glucose-6-phosphatase activity in tissue extracts.
We describe an automated, homogeneous, glucose oxidase-coupled method for the determination of glucose-6-phosphatase activity in tissue extracts. The method is based on measurement of the rate of glucose formation by the Trinder reaction, in which the end product is a quinoneimine dye which absorbs maximally at 505 nm and has a molar extinction coefficient of 5700. The incubation mixture contains 20 microL of tissue extract, 25 microL of 0.5 M phosphate buffer, pH 7.0, 175 microL of Trinder/glucose-6-phosphate reagent, and 30 microL of distilled water. After a delay period of 15 min, to exhaust any glucose endogenously present in the extract, glucose production from glucose-6-phosphate is monitored at 505 nm for 5 min in a centrifugal analyzer. The Km was 13 mM over a 10-fold range in glucose-6-phosphate concentration and the reaction was linear up to about 250 U/L. Within-run CV of the assay at activities of 48 and 190 U/L ranged between 2.5-5.0%. The between-run CV at 190 U/L was 5.1%.


[Pneumothorax in human immunodeficiency virus infected patients].
The respiratory system still continues to be a common place which deteriorates in HIV patients. Among the signs and symptoms, is the occurrence of a pneumothorax due to trauma and infections and is a cause of aggravation for these patients. The present study attempts to identify and characterise the behaviour of a group of variables in HIV patients with this complication. An observational, descriptive case series study was carried out. The desired variables were obtained from clinical records. Of the total number, 91.67% were males, and the mean age was 32.17 years. The main causes of pneumothorax were infections, particularly due to Pneumocystis jirovecii and deep venous catheterisation. A persistent statistically significant air leak was present in 33.3% of patients and two cases of pleural sepsis. Four patients died, all with acute respiratory failure and bacterial bronchopneumonia. The majority were males in the third decade of life, AIDS patients. The main causes of the pneumothorax were infections and catheterisation of the subclavian vein. Immunodepression played a significant prognostic role in the progression and outcome of the patient. Minimum pleurotomy continues to be the first treatment option in these patients, due to their precarious general state which contraindicates a major procedure. The most frequent complication was the persistent air leak, being a significant indicator of a poor prognosis in the progress of these patients. Causes of death such as acute respiratory failure and bilateral bronchopneumonia prevailed.


Studies on the properties of graphene oxide-alkaline protease bio-composites.
Graphene oxide (GO) nanosheets as functional material have a unique planar structure and intriguing mechanical that have attracted intensive interests recently. A method was developed for the immobilization protease on GO sheets using glutaraldehyde as cross-linking reagent. The results showed that the thermostability and reusability of immobilized protease have been obviously improved compared to the free enzyme. However, there was no significant change in optimum pH value between the free and immobilized protease. The immobilized protease exhibited good operational stability. The apparent K(m) and V(max) for free and immobilized alkaline protease were determined, and the bio-catalytic activity was not impaired by immobilization.


Prospective evaluation of pregnancy outcomes after gestational exposure to prazosin.
Prazosin is an antihypertensive medication which can be used to help with post-traumatic stress disorder (PTSD) symptoms. Little data is currently available on its safety in pregnancy. The aim of this study was to assess the fetal and pregnancy safety associated with prazosin exposures in early pregnancy. Subjects were 11 patients who took prazosin during pregnancy and were counselled at the FRAME clinic in London Health Sciences Centre (Ontario, Canada) between 1 January 2000 and 31 December 2021. Data on their other exposures and pregnancy outcomes were collected from medical records and through telephone questionnaires. It was found that 6/11 (54.5%) subjects did not report any adverse outcomes and experienced uneventful pregnancies. There were two miscarriages. Birthweights were within the normal range for the remaining nine pregnancies. Adverse events reported were consistent with background population expectation, including: one postpartum haemorrhage, one case of preeclampsia, one preterm birth, two NICU admissions, and two caesarean sections. For these 11 subjects, pregnancy outcomes after exposure to prazosin were consistent with typical outcomes from unexposed pregnancies. More data are needed to conclude that prazosin is safe for use in pregnant subjects. However, the lack of adverse effects above baseline is reassuring to future patients who may be unintentionally exposed to prazosin while pregnant. Therefore, this study contributes valuable data towards monitoring safety of prazosin in pregnancy.


Perceptual Modalities Guiding Bat Flight in a Native Habitat.
Flying animals accomplish high-speed navigation through fields of obstacles using a suite of sensory modalities that blend spatial memory with input from vision, tactile sensing, and, in the case of most bats and some other animals, echolocation. Although a good deal of previous research has been focused on the role of individual modes of sensing in animal locomotion, our understanding of sensory integration and the interplay among modalities is still meager. To understand how bats integrate sensory input from echolocation, vision, and spatial memory, we conducted an experiment in which bats flying in their natural habitat were challenged over the course of several evening emergences with a novel obstacle placed in their flight path. Our analysis of reconstructed flight data suggests that vision, echolocation, and spatial memory together with the possible exercise of an ability in using predictive navigation are mutually reinforcing aspects of a composite perceptual system that guides flight. Together with the recent development in robotics, our paper points to the possible interpretation that while each stream of sensory information plays an important role in bat navigation, it is the emergent effects of combining modalities that enable bats to fly through complex spaces.


Dynamics of microbial residues control the responses of mineral-associated soil organic carbon to N addition in two temperate forests.
Numerous studies have investigated the impact of nitrogen (N) addition on ecosystem carbon (C) storage and cycling. However, how N addition regulates the dynamics of different soil organic carbon (SOC) fractions and the underlying microbial mechanisms remain unclear. In this study, we assessed microbial controls (through biomass, residues and enzymes) of different SOC fractions (particulate organic carbon, POC and mineral-associated organic carbon, MAOC) in response to six years of N addition (50 kg N ha-1 yr-1) in two temperate forests (Betula platyphylla vs. Quercus wutaishanica) in Northern China. Plant inputs (root biomass and leaf litterfall) and soil chemistry (pH, extractable inorganic N, and exchangeable cations) were unaltered by N addition in both forests. In the Q. wutaishanica forest, microbial biomass, residues, and enzymes were not sensitive to N addition, which may explain the lack of response in SOC and two fractions (POC and MAOC). However, in the B. platyphylla forest, although microbial biomass and enzymes as well as SOC and POC did not significantly change after N addition, both microbial residues (amino sugars) and MAOC significantly increased after N addition. Moreover, there was a strong positive correlation between microbial residues and MAOC pool within or across the two forests. Collectively, these results suggest that the dynamics of microbial residues play a crucial role in controlling the response of mineral-associated SOC to N addition in these two forests. Separating bulk soil into distinct functional pools and considering microbial residues should help reveal the nuanced response of soil C dynamics under N addition.


Giant charge-to-spin conversion in ferromagnet via spin-orbit coupling.
Converting charge current into spin current via the spin Hall effect enables efficient manipulation of magnetization by electrical current. However, its geometrical restriction is a serious obstacle to device applications because it prevents switching of perpendicular magnetization in the absence of an external field. To resolve this issue, ferromagnetic materials have attracted attentions because their time reversal asymmetry induces magnetic-dependent charge-to-spin conversion that removes this restriction. Here, we achieved a large enhancement of magnetic-dependent charge-to-spin conversion by clarifying its mechanism. Through layer thickness dependence of the conversion efficiency, we revealed a coexistence of interfacial and bulk contributions to the magnetic-dependent charge-to-spin conversion. Moreover, the interfacial contribution to charge-to-spin conversion is found to be dominant and can be controlled via interfacial band engineering. The efficiency of charge-to-spin conversion in ferromagnet was found to be an order larger than that of other materials with reduced symmetry.


Identification of Leishmania donovani amastigotes in canine tissues by immunoperoxidase staining.
This paper describes the demonstration of Leishmania donovani amastigotes in canine tissues by immunoperoxidase staining. An indirect immunoperoxidase method was applied to the organs of 20 dogs in which leishmaniasis was previously diagnosed. Haemosiderin pigment was eliminated with 5 per cent oxalic acid. Amastigotes of L donovani appeared as dark brown stained bodies which contrasted with haematoxylin stained host cells. No positively stained amastigotes could be seen in any of the sections incubated with control serum. The organs which more frequently showed leishmanids were: skin (macrophages and fibroblasts), liver, spleen, lymph nodes and bone marrow. In a few cases amastigotes were seen in kidneys, gut, adrenal glands, eyes and testicles. This technique is simple to perform, gives consistent results and allows unequivocal histopathological diagnosis of canine leishmaniasis.


An update of juvenile animal studies in the European Union: What do the numbers say?
Concern has been raised about the number of juvenile animal studies (JAS) being conducted in the European Union (EU) and the number of species required. The question of whether there has been an increase in the number of JAS requested by European Medicines Agency (EMA) and the question of single or multiple species studies are the focus of this manuscript. All source data on Pediatric Investigation Plans (PIP) were obtained from EMA pediatrics website and evaluated by year as obtained and adjusted to the date of the original PIP agreement rather than the newly assigned date of the PIP modification. The analysis of the data originally suggested an increase in the number of juvenile animal studies per year post 2010. However, a thorough examination of the adjusted PIP data from the EMA from December 2007 through 2013 support that the number of JAS being included in PIPs per year is not increasing but is in fact fairly stable at 15-30% per year. The data also, as expected, support that the JAS are mostly proposed with a single species and that species is predominately the rat and that multi-species JAS for an agreed PIP are infrequent.


Pagetoid reticulosis in a 5-year-old boy.
We present a rare case of pagetoid reticulosis arising in a 5-year-old white boy. He had a history of a large chronic erythematous, scaly patch on his left buttock that had shown intermittent partial response to a topical antifungal medication. A punch biopsy specimen revealed dramatic epidermal hyperplasia, with parakeratosis and prominent exocytosis of single and clustered mononuclear cells (Pautrier's microabscesses) into the epidermis. Some of these exhibited hyperchromatic nuclei with irregular contours. They stained prominently for CD3, CD4, and CD8, with a predominance of CD8(+) cells. T-cell receptor gene rearrangement by polymerase chain reaction was negative for a clonal process on a second biopsy specimen that was nondiagnostic on routine sections. Pagetoid reticulosis is an indolent, unilesional variant of mycosis fungoides, in which the atypical T cells may express a CD4(-)/CD8(+) phenotype. This is in contrast to primary cutaneous epidermotropic CD8(+) cytotoxic T-cell lymphoma, which is often very aggressive with a poor outcome. Pagetoid reticulosis is exceedingly rare in children and adolescents. Two features predict a benign course in this 5-year-old child: the unilesional clinical presentation and the CD8 predominance of the epidermal lymphocytes.


Chemical profiles of the active fraction from Prinsepia utilis Royle leaves and its anti-benign prostatic hyperplasia evaluation in animal models.
The Prinsepia utilis Royle leaves (P. utilis) is a folk herb used for benign prostatic hyperplasia (BPH) control by ethnic minorities for centuries in China with rich in resources. Our previous studies have confirmed the anti-BPH effect of its water extract (QCJ) and the active fraction (Fr. B) separated from the QCJ by animal test. The Fr. B from P. utilis should be a potential candidate for BPH control. In this study, the chemical ingredients of Fr. B were identified by UPLC-QTOF-MS, and quantified by HPLC. Murine animal models were divided into 8 groups, Sham rats, BPH rats, BPH rats administered with finasteride (1 mg/kg), BPH rats administered with Pule'an (460 mg/kg), BPH rats administered with low, high dosage of QCJ (860 mg/kg, 2580 mg/kg respectively), BPH rats administered with low, high dosage of Fr. B (160 mg/kg, 480 mg/kg respectively). The expression of vascular endothelial growth factor (VEGF) in the prostate tissue of rats was tested, and serum levels of dihydrotestosterone (DHT), testosterone (T), estradiol (E2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA) in prostate homogenate were measured. One-way ANOVA followed by LSD was used for statistical analysis. The BPH rats treated by Fr. B exhibited significant reductions of VEGF and MDA levels, as well as significant increases of SOD, GSH-Px and CAT in the prostate tissue after 28 day administration (P < 0.05). Moreover, Fr. B significantly reduced DHT, DHT/E2 ratio, TNF-α, while increased T levels in serum of BPH rats (P < 0.05). UPLC-QTOF-MS analysis revealed 10 flavonoids as the key constituents of this fraction, which accounted for 54.96% of all substance of Fr. B. The relative contents of compound 1, 2 are 11.1%, 13% in Fr. B respectively. These results indicated that the Fr. B obtained from P. utilis alleviated the symptoms of BPH rats through multiple mechanisms including reduction of DHT/E2 ratio, inhibition of growth factor, anti-inflammation and anti-oxidation, in which flavonoids might be the key constituents. It supported the hypothesis that the Fr. B should be further explored as a candidate for BPH patients.


Placental fibronectin staining is unaffected in pregnancies complicated by late-onset intrauterine growth restriction and small for gestational age fetuses.
To investigate the placental staining pattern of fibronectin, an extracellular matrix protein essential for trophoblastic invasion, in pre-eclampsia and fetal growth restriction. This was a retrospective study conducted at the University of Udine, including the placentas of women with pre-eclampsia and fetal growth restriction collected between January 1, 2001, and December 31, 2010. Fibronectin was evaluated in placental tissue micro-array by immunohistochemistry, describing localization and intensity of staining. The study included the placentas of 36 women with early-onset (delivery <34 weeks of gestation) pre-eclampsia; 6 with early-onset HELLP syndrome; 17 with early-onset intrauterine growth restriction (IUGR); 14 with late-onset (delivery ≥34 weeks of gestation) pre-eclampsia; 35 with late-onset IUGR; 18 with small for gestational age (SGA) fetuses (birth weight <10th percentile); and 64 controls. Fibronectin was present both at the cell surface and in the cytoplasm. Cytoplasm staining intensity resulted higher in early forms of pregnancy-related complications compared to controls, although this was statistically significant (P<0.05) only for early-onset pre-eclampsia (P=0.085 for HELLP syndrome; P=0.091 for IUGR). Also, late-onset forms of pre-eclampsia had stronger cytoplasmic and pericellular staining compared to controls (P<0.05). Interestingly, staining of both late-onset IUGR and SGA was comparable to controls. Fibronectin appeared to be unaffected in women with late-onset IUGR and SGA fetuses, suggesting a peculiar common pathogenetic pattern in these conditions.


The impact of acute renal failure on early and late outcomes after thoracic aortic endovascular repair.
The incidence of acute kidney injury (AKI) after thoracic aortic endovascular repair (TEVAR) is variably reported at 1% to 34%. This study utilized the RIFLE (risk, injury, failure) criteria to evaluate the incidence, risk factors, and late implications of AKI after TEVAR. In all, 350 patients without prior dialysis requirement underwent TEVAR (1993 to 2013). The mean age was 68.7 years (54% male). The mean preoperative glomerular filtration rate was 76.5 ± 37.6 mL/min, with 39 patients (11.7%) in chronic kidney stage 3 or 4. The TEVAR was performed for rupture in 20.6%. The mean contrast volume administered was 95.7 ± 52.9 mL. Early mortality was seen in 17 patients (4.9%). Acute kidney injury defined as RIFLE classes risk, injury, or failure was seen in 59 patients (17%; risk = 36, injury = 14, failure = 9). Independent predictors of AKI included history of saccular aneurysm, presentation with rupture, or need for arch repair or red blood cell transfusion (all p < 0.05). Only 2 patients (0.6%) needed dialysis, with none requiring permanent dialysis. Importantly, 10-year freedom from dialysis was 97.7%. Development of AKI predicted early mortality (p < 0.001, odds ratio 9.8). Ten-year survival was 38.1%. Both injury and failure AKI classes independently predicted late mortality (p < 0.05). The prevalence of AKI after TEVAR as assessed by RIFLE criteria is higher than seen in previous reports. Despite its infrequent progression to permanent dialysis dependence, AKI remains an important risk factor for both early and late mortality. Future studies should evaluate strategies to reduce the incidence of AKI after TEVAR to improve both early and late outcomes.


Dispersive liquid-liquid microextraction based on deep eutectic solvent for elemental impurities determination in oral and parenteral drugs by inductively coupled plasma optical emission spectrometry.
A simple, fast, sensitive and green pretreatment method for determination of Cd, Co, Hg, Ni, Pb and V in oral and parenteral drug samples using inductively coupled plasma optical emission spectrometry (ICP OES) has been developed. According to United States Pharmacopoeia (USP), those metals must be reported in all pharmaceutical products for quality control evaluation (i.e., elemental impurities from classes 1 and 2A of USP Chapter 232). To improve the analytical capabilities of ICP OES, a dispersive liquid-liquid microextraction (DLLME) has performed using a safe, cheap and biodegradable deep eutectic solvent (DES) as extractant solvent (a mixture of 2:1 M ratio of DL-menthol and decanoic acid). Seven parameters affecting the microextraction efficiency have carefully optimized by multivariate analysis. Under optimized conditions, the DES-based DLLME-ICP OES procedure improved limit of quantitation (LOQ) values on range from 12 to 85-fold and afforded an enrichment factor on average 60-times higher than those obtained to direct ICP OES analysis. Consequently, LOQ values for Cd, Co, Hg, Ni, Pb and V have been on average 10-times lower than target limits recommended for drugs from parenteral route of administration. Trueness has evaluated by addition and recovery experiments following USP recommendations for three oral drug samples in liquid dosage form and three parenteral drugs. Recovery and RSD values have been within the range of 90-109% and 1-6%, respectively. All analytes were below the respectives LOQ values, hence, lower than the limits proposed by USP Chapter 232.


Determination of intrinsic affinity constants of monoclonal antibodies against carcinoembryonic antigen.
A 2-phase method is described for the determination of the intrinsic affinity constants (K-values) for the interaction between monoclonal antibodies (MAbs) against carcinoembryonic antigen (CEA) and CEA. The Mabs were coupled covalently to CNBr-activated paper discs. MAb coupled discs and a 2-fold dilution series of 125I-CEA were incubated at 20 degrees C until equilibrium was reached. Nonlinear curve-fitting was used for estimation of K-values and different calculation models were thereby tested. The K-values for 12 different anti-CEA MAbs were determined to be 0.3-52 X 10(6) M-1, which is 1-2 orders of magnitude lower than the values obtained in a previous study with some of these MAbs using the ammonium sulphate method to separate free from bound antigen. The K-values obtained by the paper disc method are probably better estimates of the intrinsic association constant than those obtained previously. There are two main reasons for this: (1) free and bound antigen are separated from each other under physiological conditions and (2) the opportunity for multipoint interaction between MAb and CEA is minimized when the MAb is coupled to a rigid carrier substance. Thus, even when the MAb reacts with greater than or equal to 2 epitopes in CEA, as seems to be the case with several of our anti-CEA MAbs, the intrinsic K-value should be obtained. The fundamental validity of 2-phase assays, sometimes questioned in the literature, is demonstrated.


Long-term prognostic benefit of field triage and direct transfer of patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.
Direct transfer (DT) to the catheterization laboratory has been demonstrated to reduce delays in primary percutaneous coronary intervention (PPCI). However, data with regard to its effect on long-term mortality are sparse. The aim of this study was to investigate the effect of DT on long-term mortality in patients with ST-segment elevation myocardial infarctions treated with PPCI. A cohort study was conducted of 1,859 patients (mean age 63.1 ± 13 years, 80.2% men) who underwent PPCI from May 2005 to December 2010. From the whole series, 425 patients (23%) were admitted by DT and 1,434 (77%) by emergency departments. DT patients were younger (mean age 61 ± 12 vs 64 ± 12 years, p = 0.017), were more frequently men (86% vs 76%, p = 0.001), and had a higher proportion of abciximab use (77% vs 64%, p <0.0001). The DT group had a shorter median contact-to-balloon time (105 vs 122 minutes, p <0.0001) and a shorter time to treatment (185 vs 255 minutes, p <0.0001) compared with the emergency department group. Thirty-day and long-term mortality (median follow-up 2.4 years, interquartile range 1.6 to 3.2) were lower in the DT group (3% vs 6%, p = 0.049, and 9.4% vs 14.4%, p = 0.008, respectively). An adjusted Cox regression analysis proved that the DT group had an improved prognosis during follow-up (hazard ratio 0.71, 95% confidence interval 0.50 to 0.99). In conclusion, DT of patients with ST-segment elevation myocardial infarctions for PPCI was associated with fewer delays and improved survival. This benefit was maintained after long follow-up. This strategy should be emphasized in all networks of ST-segment elevation myocardial infarction care.


The Prevalence of Abnormal Spinopelvic Relationships in Patients Presenting for Primary Total Hip Arthroplasty.
The prevalence of an abnormal spinopelvic relationship in patients presenting for primary total hip arthroplasty (THA) is not well known. The purpose of this study was to identify the prevalence of abnormal spinopelvic relationships in patients presenting for primary THA. A retrospective chart review of 338 consecutive, nonselected patients undergoing primary THA from the practice of 2 fellowship-trained adult reconstruction surgeons was performed (J.E.O. and T.S.B.). Sitting and standing radiographs were measured for lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SSstand), and pelvic tilt; the sacral slope was also measured on sitting radiographs (SSsit). Patients were assessed for the presence of spinopelvic imbalance, defined as PI-LL>10°, and decreased spinopelvic motion, defined as SSstand-SSsit< 10°. Descriptive statistics were reported. A cohort of 338 patients was identified; 110 were excluded. In total, 228 unique patients underwent measurement. One hundred one of 228 patients (44.3%) in the cohort were female. The mean age of the cohort was 60.0 ± 13 years, with the mean body mass index of 31 ± 7 mg/kg2. Spinopelvic imbalance (PI-LL > 10°) was present in 142 of 228 patients (62.3%). Decreased motion at the spinopelvic junction (SSstand-SSsit < 10°) was present in 78 of 228 patients (34.2%). Fifty (21.9%) patients had both spinopelvic imbalance and decreased spinopelvic motion. In a cohort of 228 patients presenting for primary THA, the prevalence of spinopelvic imbalance was 62.3%, the prevalence of decreased spinopelvic motion was 34.2%, and the prevalence of both spinopelvic imbalance and decreased spinopelvic motion was 22%. Hip surgeons are likely to encounter patients with abnormal spinopelvic relationships.


Constructing 24(23→22)-abeo-Cholestane from Tigogenin in a 20(22→23)-abeo-Way via a PhI(OAc)2-mediated Favorskii Rearrangement.
Transforming tigogenin, a steroidal sapogenin, to a 24(23→22)-abeo-cholestane, which is an unusual structural feature shared by the aglycons of saundersiosides and candicanoside A, is described. The spiroketal of tigogenin was unfolded and the resulting C22-ketone was subjected to Favorskii rearrangement mediated by PhI(OAc)2/KOH/MeOH to squeeze out the C22 from the side chain, thus reaching the 24(23→22)-abeo-cholestane structure.


Scintigraphic evaluation of enterogastric reflux using 75Se-HCAT: methodology and first clinical observations.
The aim of this study was to assess the possibility of detecting enterogastric reflux (EGR) by 75Se-HCAT cholescintigraphy. The lowest detectable activity in the gastric area at different concentrations of the radiotracer in the gallbladder was preliminary measured both in a plastic phantom and in an in vivo model. Ten patients were studied after a single oral administration of 1480 KBq 75Se-HCAT. Gamma camera imaging was carried out for five consecutive days during both fasting and after meal ingestion. In our in vivo model an EGR corresponding to 1% of gallbladder content on day one and 8% on day five was detected. In three out of five patients in whom bile was present in the stomach at endoscopy, 75Se-HCAT cholescintigraphy demonstrated an EGR, while in three out of five patients in whom endoscopy was negative, 75Se-HCAT cholescintigraphy detected EGR either during fasting or after meal ingestion. As EGR is not constant, 75Se-HCAT may be a useful tracer of bile to detect EGR over a prolonged period of time and in different physiological conditions.


Management of complications of congenital hand disorders.
This article reviews treatment and presents complications seen in the treatment of 7 common congenital hand differences, including syndactyly, camptodactyly, ulnar and radial polydactyly, thumb hypoplasia, radial longitudinal deficiency, and epidermolysis bullosa. The management of these conditions is challenging but has evolved over the last several decades with refined understanding of the disease processes and treatments. The goal of this article is to synthesize prior knowledge and provide further insights into these conditions that will help the surgeon avoid treatment complications.


An analysis of thymic function and the possible role of the thymus in stem cell production.
The thymus is considered to be essentially an organ of the immune system, its purpose being to supply T cells. The role of the T cell is to regulate the immune reaction which it does by liberating lymphokines. The lymphokine function of the T cells was not deciphered in vivo, but in explanted T cells, and it is debatable if explanted cells behave in the same way as their counterparts in the intact animal, so the liberated lymphokines may not represent nature's intent. Adding to the disquiet are those biological properties of the thymus which are difficult to explain on an immunological basis, in particular why the thymus is essential in the child but not in the adult. Thus, there is room for a different approach to the role of the thymus. There is sound evidence that the thymus plays a part in somatic growth and differentiation, and one explanation is that the thymus provides the stem cells for somatic growth. A stem cell role is supported by studies on mastopoiesis and eosinophilopoiesis, and also supported by the way embryonic organs grow after their initial development. From the arguments put forward, the hypothesis is put that the role of the thymus is to store and propagate the stem cells required for the organ growth which takes place subsequent to their initial development. If the thymus is a repository for stem cells, the varied aspects of thymic behaviour, including its role in immunity, can be explained.(ABSTRACT TRUNCATED AT 250 WORDS)


Feyerabend's perspectivism.
Although, Feyerabend himself seems never to have used the term 'perspectivism' to designate a philosophical position, I think his views about science are very well characterized as perspectival. In fact, his later writings contain much that contributes to current thinking about perspectivism. I would like, therefore, to distinguish my own perspectivism from Feyerabend's. In the end, I will argue, his perspectivism is lacking enough of the critical bite that the younger Feyerabend found so attractive in Popper's philosophy.


An in vitro comparison of dentifrice formulations in three distinct oral microbiotas.
In vitro biofilm models, representative of some aspects of nascent, supra-gingival plaques (Hydroxyapatite Disc Biofilm Models), developed supra-gingival plaques (Modified Drip-flow Biofilm Reactors) and sub-gingival plaques (Multiple Sorbarod Devices) were used to compare the antimicrobial effects of a triclosan-containing dentifrice with a stannous fluoride and zinc lactate combination. Triplicate salivary biofilm microcosms were maintained for 2d (hydroxyapatite discs), 5d (Sorbarods) or up to 6d (drip flow reactors). Dentifrice slurries (10%, w/v) were added once to the discs and repeatedly to the Drip Flow Reactors and Sorbarods. Plaques were analysed by differential culture and gravimetrically. Whilst both dentifrices were comparably effective at reducing viability and plaque accumulation in mature supragingival plaques, the triclosan dentifrice produced comparatively larger reductions in total streptococci and anaerobes in nascent plaques (p<0.05) and greater reductions in Gram-negative anaerobes and streptococci in subgingival plaques. We have used a multi-model approach to determine the effectiveness and specificity of dentifrices against compositionally distinct plaques. Whilst both formations reduced bacterial viability and plaque accumulation, their effects could be differentiated in nascent and deep plaques where the triclosan dentifrice caused larger viability reductions.


8OHdG is not a biomarker for Huntington disease state or progression.
To evaluate plasma 8-hydroxy-deoxy-guanosine (8OHdG) levels as a potential biomarker of premanifest and early Huntington disease (HD). Personnel from 2 independent laboratories quantified 8OHdG in blinded longitudinal plasma samples taken 24 months apart from 160 TRACK-HD participants, as well as samples containing control plasma with added ("spiked") 8OHdG. One laboratory used a liquid chromatography-electrochemical array (LCECA) assay, and the other used liquid chromatography-mass spectrometry (LCMS). The LCMS assay was more accurate than the LCECA assay for measurements of "spiked" 8OHdG levels in plasma. Neither assay demonstrated cross-sectional differences in plasma 8OHdG among controls, premanifest HD, and early symptomatic HD. Similarly, neither assay showed longitudinal changes in any disease group over 24 months. Plasma concentration of 8OHdG is not a biomarker of disease state or progression in HD. We recommend that future putative biomarker studies use blinded sample analysis, standard curves, independent analytical methods, and strict quality control of sample collection and storage.


Adsorption properties and influencing factors of Cu(II) on polystyrene and polyethylene terephthalate microplastics in seawater.
As an emerging contamination in the ocean, microplastics can act as effective vectors of pollutants, the ecological risks caused by the combined pollution of microplastics and other pollutants have attracted growing attention. In this work, Copper (Cu(II)) was chosen as the classic pollutant, polystyrene (PS) and polyethylene terephthalate (PET) pellets were used as the typical marine microplastics, the adsorption performance of Cu(II) on PS and PET beads was investigated by adsorption kinetics and isotherm experiments, and other influencing conditions, such as pH, salinity, coexisting heavy metals ions and aging treatment, were evaluated. The results indicated that the adsorption behavior of Cu(II) on PS and PET was spontaneous and endothermic in the simulated seawater environment, and the batch experimental data can be effectively described by pseudo-second-order model and Freundlich isothermal model. Besides, the adsorption capacity of microplastics for Cu(II) was the best at pH 7, the change of salinity had no obvious effect on the adsorption in the natural marine environment. Moreover, co-existence of lead (Pb(II)) exhibited evident impacts on Cu(II) sorption onto PS and PET, which confirmed the adsorption competition effect between them. Additionally, high temperature aging treatment of microplastics in different environments for different duration time could obviously affect the properties of microplastics. It was found that the microplastics after being exposed to high temperature environment in the air for 168 h showed relatively stronger adsorption amount for Cu(II). In summary, these findings suggested that electrostatic interaction and distributed diffusion mechanisms may be the main mechanisms of adsorption, while no new functional groups were generated after the adsorption, indicating that physisorption may dominate the adsorption performance of PS and PET pellets for Cu(II). This study provides supplementary insights into the role of microplastics as carriers of heavy metals in the marine environment.


Developmental antecedents of borderline personality disorder.
Developmental antecedents of borderline personality disorders (BPDs) were examined in 25 DSM-IV-diagnosed subjects with BPD and 107 non-borderline control subjects on the basis of medical records and 28 years follow-up. Abuse, neglect, environmental instability, paternal psychopathology, and lower score on protective factors differentiated significantly between the groups. Environmental instability and lower score on protective factors such as artistic talents, superior school performance, above average intellectual skills, and talents in other areas were found to be independent predictors of BPD diagnosis. The results of this study suggest that both abuse and neglect, unpredictable and unstable early environment, as well as deficit in protective factors may substantially contribute to the development of BPD in persons constitutionally predisposed for the disorder. The results of the study also suggest that future research should address the impact of social and cultural context, as well as the absence of protective factors, on the development of the BPD.


Significance of postoperative serum thyroglobulin levels in patients with papillary and follicular thyroid carcinomas.
Although there are many factors that affect postoperative serum levels of thyroglobulin (Tg), such levels have been previously used to detect recurrence of papillary and follicular thyroid carcinomas. This study was conducted to elucidate the significance of postoperative levels of Tg in patients with clinical presentations of papillary thyroid carcinoma, follicular thyroid carcinomas, or both. To collect data pertaining to patients with thyroid cancer who were treated in Chang Gung Medical Center in Linkou, Taiwan, records relating to a total of 847 patients with pathologically verified papillary or follicular thyroid cancer, all of whom received total thyroidectomy and thyroid remnant ablation with radioactive iodide ((131)I), were studied. To evaluate the clinical significance of postoperative levels of Tg, the patients were categorized into three groups based on postoperative Tg level. Group A was classified as those demonstrating a 1-month postoperative Tg levels less than 1 ng/ml. Group B patients were classified as those displaying a 1-month postoperative Tg levels greater than or equal to 1 ng/ml, but less than 10 ng/ml. Group C patients were classified as those exhibiting a 1-month postoperative Tg levels great than or equal to 10 ng/ml. Of the patients in group A, none presented with distant metastases at the time of diagnosis or during the follow-up period. In group B, 15 patients (3.5%) died of thyroid cancer. In this group, tumor size was an important factor in cancer-related mortality, diagnostic clinical class, and follow-up status. Of the 491 patients in group C, 49 (10.0%) patients died of thyroid cancer. Among the patients in group C, age, histopathologic type, stage of diagnosis, and follow-up Tg values were important factors. Among groups A, B, and C, there were 161 (95.8%), 253 (76.4%), and 129 (37.1%) patients, respectively, with disease-free status at the end of 1998. Postoperative serum Tg levels can be used as a prognostic indicator in patients with papillary and follicular thyroid cancer. For patients with Tg levels greater than or equal to 10 ng/ml, Tg levels are a useful marker to predict prognosis.


Monocytes are required for optimum in vitro stimulation of bovine peripheral blood mononuclear cells by non-methylated CpG motifs.
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs within certain flanking base pairs are recognized as a danger signal by the innate immune system of vertebrates. Using lymphocyte proliferative response (LPR) and IFN-gamma secretion assays, a panel of 38 ODN was screened for immunostimulatory activity on bovine peripheral blood mononuclear cells. ODN composed of a nuclease resistant phosphorothioate backbone and a leading 5'-TCGTCGTT-3' motif with two 5'-GTCGTT-3' motifs were highly stimulatory in both assays. Flow cytometric analysis and cell-specific surface marker labeling determined that B-cells (surface IgM(+)) were the primary cell population responding in the LPR assay. Depletion of T cells (CD3(+)) from the PBMC population did not affect IFN-gamma secretion or B-cell proliferation when cultured with CpG-ODN. However, depletion of monocytes (DH59B(+)) completely abrogated the ability of CpG-ODN to stimulate IFN-gamma secretion, and significantly reduced the B-cell proliferative response. These data establish the identity of an optimal immunostimulatory CpG motif for cattle and demonstrate that monocytes play a pivotal role in the ability of cell populations to respond to CpG-ODN. These data provide insight for future studies investigating the mechanism of CpG-ODN bioactivity and its application in novel vaccine formulations and immunotherapy.


Familial syndrome of mental retardation, short stature, contractures of the hands, and genital anomalies.
Two teen-age XY brothers with mental retardation, short stature, obesity, genital abnormalities, and contractures of their hands are described. They have generalized osteoporosis and a history of frequent fractures. Their endocrinologic evaluation was normal except for mild glucose intolerance and delayed, but normal puberty. Although these brothers are similar to individuals with Prader-Willi syndrome, their unusual hand contractures, clinically significant osteoporosis, and lack of hypotonia indicate that they represent a different entity.


MiR-155 aggravated septic liver injury by oxidative stress-mediated ER stress and mitochondrial dysfunction via targeting Nrf-2.
Liver is uniquely vulnerable during sepsis. MicroRNA-155 (miR-155) is confirmed to play crucial roles in septic liver injury. The present study aims to investigate the mechanisms of miR-155 in septic liver injury. The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) in mice. Mice were divided into four groups: Vehicle, miR-155 antagomir, LPS, LPS+ miR-155 antagomir. The survival rate and body weight were monitored. Liver injury was assessed by H&E staining. The levels of serum ALT and inflammatory cytokines were determined by ELISA kits. Oxidative stress was detected by MDA and SOD detection kits. The miR-155, Nrf-2, and markers related to oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial injury and apoptosis were detected by western blotting and qPCR. Apoptosis in liver tissues was detected by TUNELstaining. MiR-155 antagomir alleviated liver injury as evidenced by enhancing survival rate and body weight, inhibiting inflammatory cell infiltration, liver cells necrosis and decreasing ALT level. The productions of TNF-α, IL-6 were suppressed, while anti-inflammatory cytokine IL-10 was promoted by miR-155 antagomir. Oxidative stress was inhibited by miR-155 antagomir via enhancing nuclear factor, erythroid 2-like 2 (Nrf-2) expression. ER stress and Cytochrome C (Cyto-C) release were restrained by miR-155 antagomir. Sepsis-induced apoptosis was repressed by miR-155 antagomir as manifested by the decreased levels of Bax, cleaved caspase-12, 9 and 3, and increased levels of Bcl-2 and uncleaved PARP. MiR-155 antagomir relieved septic liver injury through inhibiting oxidative stress-mediated ER stress, mitochondrial dysfunction and apoptosis via targeting Nrf-2, suggesting miR-155 as a therapeutic target for septic liver injury.


The struggle for wholeness: addressing individual and collective trauma in violence-ridden societies.
The present article begins with an overview of how staff at the Center for Dialogue and Human Wellbeing (CDBH)-at Tecnológico de Monterrey University in Chihuahua, México-approach the process of conflict transformation. Specifically, it focuses on CDBH's strategies for dealing with historical injury, as well as the individual and collective trauma existing between and among communities engaged in ongoing conflict. It proceeds to examine how traumatic memories are stored in the mind/brain, and how trauma can impact on individuals and communities locked into a cycle of violence. The ensuing section provides an overview of the debate and the literature concerning psychotherapeutic and holistic-kinesthetic approaches for addressing individual and collective trauma. A hypothetical workshop is then offered to give readers a clear idea of how trauma work is actually carried out. The article ends by asking what approaches can best be applied for transforming collective trauma into sacred memories, which can become the driving force for a continuing commitment to building and sustaining peace among segments of communities that had previously been in conflict with one another.


Inhibition of lncRNA XIST Improves Myocardial I/R Injury by Targeting miR-133a through Inhibition of Autophagy and Regulation of SOCS2.
The objective of this study was to investigate the role of lncRNA XIST and its relationship with miR-133a in myocardial I/R injury. H9C2 cells treated by hypoxia/reoxygenation (H/R) were used to establish an in vitro I/R model. The small interfering RNA (siRNA) for XIST and miR-133 mimics, inhibitor, and suppressor of cytokine signaling (SOCS2) recombinant plasmids were used to transfect the cells. Cell apoptosis was determined by flow cytometry analysis, and cell viability was used for 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT) assay. The dual-luciferase reporter assay was performed to confirm binding between XIST and miR-133a, as well as miR-133a and SOCS2. To inhibit or overexpress XIST, miR-133a, or SOCS2 in I/R mice, we used recombinant lentivirus vectors and adenovirus vectors for tail vein injection. The expression of XIST, miR-133a, and SOCS2 was determined by quantitative real-time PCR, and LC3 I/II and Beclin1 was determined by western blotting. The expression of XIST and SOCS2 was significantly upregulated, whereas the miR-133a level was remarkably downregulated in both H/R H9C2 cells and I/R mice myocardial tissues. In both H/R H9C2 cells and I/R mice, the inhibition of XIST led to decreased apoptosis and autophagy, and inhibition of miR-133a reversed these effects. Similarly, overexpression of miR-133a resulted in reduced apoptosis and autophagy, which were reversed by overexpression of SOCS2. The inhibition of XIST and overexpression of miR-133a also promote cell viability of H/R cells. The dual-luciferase reporter assay significantly showed that XIST directly targeted on miR-133a, and miR-133a directly targeted on SOCS2. The inhibition of XIST could improve myocardial I/R injury by regulation of the miR-133a/SOCS2 axis and inhibition of autophagy.


A non-invasive method for fractionated stereotactic irradiation of brain tumors with linear accelerator.
A new technique for fractionated stereotactic irradiation of intracranial lesions is described. The treatment is based on a versatile, non-invasive interface for stereotactic localization of the brain target imaged by computed tomography (CT), angiography or magnetic resonance tomography (MRT), and subsequent repetitive stereotactic irradiation of the target using a linear accelerator. The fractionation of the stereotactic irradiation was intended to meet the requirements of the basic principles of radiobiology. The radiophysical evaluation using phantoms, and the clinical results in a small number of patients, demonstrated a good reproducibility between repeated positionings of the target in the isocenter of the accelerator, and a high degree of accuracy in the treatment of brain lesions.


Biological investigation of the platinum(II)-[*I]iodohistamine complexes of potential synergistic anti-cancer activity.
Cisplatin chemotherapy in combination with external irradiation or with low-dose continuous internal radiotherapy produces significant supra-additive treatment effects towards several tumor cells. The purpose of our research is to develop a new class of platinum-based anticancer drugs containing moieties of synergistic potency such as platinum core and a radiotherapeutic isotope which, delivered directly to the tumorous cells by a specifically designed vectors, should produce a local enhancement of therapeutic dose. Thus, we have synthesized a new platinum-iodohistamine complex and its radioactive analogues labeled with I-125 and I-131. In the present study some biological properties of those compounds have been investigated. The in vitro screening study pointed out that non-radioactive platinum-iodohistamine complex possesses high cytostatic activity against COLO-205 cells, and moderate activity against HL-60 cell line. No cytotoxicity was observed against MOLT-4 and L-1210 cells, as well as against VERO normal cells. The biodistribution of intravenously administered radioactive platinum-[131I]-iodohistamine complex to normal rats revealed the highest accumulation in the liver (c.a. 40%ID). Intraperitoneal injections of the complex to tumor-bearing C3H mice resulted in scattering of the dose in the organs (mainly in GIT, liver, kidney). The retention of radioactive complex in neoplastic tissue was 3-4 times higher than in normal muscular tissue, although exhibited the tendency to decrease with time post injection. The results of the present study show promising features of the newly developed platinum-iodohistamine complexes and justify prospective investigation of in vivo anticancer potency on animal models of solid tumors.