Priorities and Progress in Gram-positive Bacterial Infection Research by the Antibacterial Resistance Leadership Group: A Narrative Review.
The Antibacterial Resistance Leadership Group (ARLG) has prioritized infections caused by gram-positive bacteria as one of its core areas of emphasis. The ARLG Gram-positive Committee has focused on studies responding to 3 main identified research priorities: (1) investigation of strategies or therapies for infections predominantly caused by gram-positive bacteria, (2) evaluation of the efficacy of novel agents for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, and (3) optimization of dosing and duration of antimicrobial agents for gram-positive infections. Herein, we summarize ARLG accomplishments in gram-positive bacterial infection research, including studies aiming to (1) inform optimal vancomycin dosing, (2) determine the role of dalbavancin in MRSA bloodstream infection, (3) characterize enterococcal bloodstream infections, (4) demonstrate the benefits of short-course therapy for pediatric community-acquired pneumonia, (5) develop quality of life measures for use in clinical trials, and (6) advance understanding of the microbiome. Future studies will incorporate innovative methodologies with a focus on interventional clinical trials that have the potential to change clinical practice for difficult-to-treat infections, such as MRSA bloodstream infections.


Study on the construction and practice of blended teaching mode of emergency first aid specialty based on OBE concept.
Outcome-based education (OBE) has changed the previous teacher-centered education model. This study was performed to evaluate the effect of practice of blended teaching mode of emergency first aid specialty based on OBE concept in teaching. In this study, 23 undergraduate students (observation group) at the level of 2017 and 23 undergraduate students (control group) at the level of 2016 majoring in emergency medicine who take part in clinical practice were selected as the study subjects. By setting the expected learning achievement goals in 6 aspects, the mixed teaching method is used to reorganize teaching content and carry out teaching evaluation, and a mixed OBE concept teaching model is constructed and implemented. The number of high scoring students with a score above 90, the number of pass subjects, and the mean score at the class level were significantly improved compared with those who practiced the traditional teaching mode. At the 3 time points of pre internship, in practice and after post internship, the achievement of the 6 expected learning outcomes (19.92 ± 3.68, 23.89 ± 2.93, 25.44 ± 3.33, F = 77.87, P < .001) and critical thinking abilities (283.39 ± 25.84, 287.43 ± 24.33, 300.07 ± 23.87, F = 49.82, P < .001) were significantly improved. Blended teaching mode of emergency first aid specialty based on OBE concept significantly improved education.


Airway area distribution from the forced expiration maneuver.
The maximal expiratory flow-volume (MEFV) maneuver is a commonly used test of lung function. More detailed interpretation than is currently available might be useful to understand disease better. We propose that a previously published computational model (Lambert RK, Wilson TA, Hyatt RE, and Rodarte JR. J Appl Physiol 52: 44-56, 1982) can be used to deduce, from the MEFV curve, the serial distribution of airway areas in the larger airways. An automated procedure based on the simulated annealing technique was developed. It was tested with model-generated flow data in which airway areas were reduced one generation at a time. The procedure accurately located the constriction and predicted its size within narrow bounds when the constriction was in the six most central generations of airways. More peripheral constrictions were detected but were not precisely located, nor were their sizes accurately evaluated. Airway areas of generations upstream of the constriction were usually overestimated. The procedure was applied to spirometric data obtained from eight volunteers (4 asthmatic and 4 normal subjects) at baseline and after methacholine challenge. The predicted areas show individual differences both in absolute values, and in relative distribution of areas. This result shows that detailed information can be obtained from the MEFV curve through the use of a model. However, this initial model, which lacks airway smooth muscle, needs further refinement.


Interaction of Mitochondria with the Endoplasmic Reticulum and Plasma Membrane in Calcium Homeostasis, Lipid Trafficking and Mitochondrial Structure.
Studying organelles in isolation has been proven to be indispensable for deciphering the underlying mechanisms of molecular cell biology. However, observing organelles in intact cells with the use of microscopic techniques reveals a new set of different junctions and contact sites between them that contribute to the control and regulation of various cellular processes, such as calcium and lipid exchange or structural reorganization of the mitochondrial network. In recent years, many studies focused their attention on the structure and function of contacts between mitochondria and other organelles. From these studies, findings emerged showing that these contacts are involved in various processes, such as lipid synthesis and trafficking, modulation of mitochondrial morphology, endoplasmic reticulum (ER) stress, apoptosis, autophagy, inflammation and Ca 2 + handling. In this review, we focused on the physical interactions of mitochondria with the endoplasmic reticulum and plasma membrane and summarized present knowledge regarding the role of mitochondria-associated membranes in calcium homeostasis and lipid metabolism.


Organocatalytic asymmetric epoxidation reactions in water-alcohol solutions.
The diastereo- and enantioselective organocatalytic epoxidation of alpha,beta-unsaturated aldehydes in aqueous solutions is presented. By the screening of the reaction conditions for the epoxidation of cinnamic aldehyde applying hydrogen peroxide as the oxidant and 2-[bis-(3,5-bis-trifluoromethyl-phenyl)-trimethylsilanyloxy-methyl]-pyrrolidine as the catalyst, a highly stereoselective reaction has been developed. The scope of the diastereo- and enantioselective organocatalytic epoxidation in aqueous solutions is documented by the asymmetric epoxidation of alpha,beta-unsaturated aldehydes with enantioselectivities up to 96% ee.


Effects of Statin Therapy on Exercise Levels in Participants in the National Runners' and Walkers' Health Study.
To determine whether decreases in exercise 1) were greater in individuals who were diagnosed as having hypercholesterolemia than in those without the diagnosis during follow-up and 2) were greater in incident hypercholesterolemic participants starting statins than in those not treated with cholesterol-lowering medications. Regression analyses of changes since baseline (Δ) in exercise vs diagnosis of hypercholesterolemia and its treatment in 66,377 runners and 12,031 walkers not using cholesterol medications at baseline who were resurveyed during the National Runners' and Walkers' Health Study follow-up (January 1, 1991, through December 31, 2006). A total of 3510 runners began statin treatment, 1779 began other or unspecified cholesterol-lowering drug treatment, and 2583 had untreated hypercholesterolemia; 58,505 runners remained nonhypercholesterolemic controls during the mean 7.2-year follow-up. Usual distance run decreased significantly more in hypercholesterolemic runners who began taking statins (mean ± SE: -0.47±0.06 km/d) than in runners who remained nonhypercholesterolemic during follow-up (-0.08±0.02 km/d) (P<.001). However, running distance also decreased significantly more in hypercholesterolemic runners who began unspecified/other (-0.52±0.08 km/d) or no (-0.47±0.07 km/d) cholesterol drugs than in nonhypercholesterolemic runners during follow-up. Moreover, Δrunning distance did not differ significantly between hypercholesterolemic runners who were statin treated vs those treated with other/unspecified (P=.64) or no (P=.94) cholesterol drugs. Initiating statin therapy was not associated with Δrunning pace in hypercholesterolemic runners or Δwalking distances in hypercholesterolemic walkers. These results are consistent with the premise that a decrease in running distance is associated with hypercholesterolemia and do not suggest that statins reduce exercise level or intensity.


A prospective study of weight maintenance in obese subjects reduced to normal body weight without weight-loss training.
We examined the pattern of weight maintenance in 24 obese women [body mass index (BMI; in kg/m2) 27.6 +/- 0.4 who were provided foods for a balanced deficit diet until each had lost > or = 10 kg and attained normal body weight (BMI 22.9 +/- 0.4). At 1 y subjects had regained a mean of 42% of their weight loss, which increased to 87% at 4 y. At 4 y 44% of patients had regained < 75%, whereas 37% had regained > or = 100% of the weight originally lost. The amount of weight gained was markedly different from that observed in 24 pair-matched never-obese control subjects over the same length of follow-up. Because the results reported herein were obtained without teaching the subjects weight-control skills, they may be regarded as reflective of the natural history of weight maintenance in this population and may serve as a reference for various weight-intervention programs. The pattern of weight rebound observed in this study is very similar to the pattern observed in combined results from published diet and behavioral-modification programs, which raises important questions regarding the efficacy of these approaches in long-term weight maintenance.


Bioactive constituents from seeds of Annona Senegalensis Persoon (Annonaceae).
Column chromatography led to the isolation and full characterization of N-cerotoyltryptamine (1) previously described in a mixture of 5 compounds, asimicin (2) and ent-19-Carbomethoxykauran-17-oic acid (3) isolated from this species for first time alongside stigmasterol glycoside (4) and lacceroic acid (5). The structures of the compounds were established by extensive EIMS, HRESIMS, 1 D and 2 D NMR studies. Compound 1 and the extract AS were more potent inhibitors of ROS with IC50 values of 2.7 ± 0.1 µg/mL and 8.7 ± 10.2 µg/mL respectively than Ibuprofen (11.2 ± 1.9 µg/mL) as a standard anti-inflammatory drug. Compound 2 showed high inhibition on nitric oxide (IC50 = 3.9 ± 0.2 µg/mL), almost 6 times more active than the standard compound L-NMMA (IC50 = 24.2 ± 0.8 µg/mL) used. Compounds showed relatively low toxicity on NIH-3T3 fibroblast cells compared to standard. The results indicate that compounds 1 and 2 are potent anti-inflammatory drug candidates.


A case of pseudoadenomatous hyperplasia of ciliary body epithelium successfully treated by local resection.
A case of pseudoadenomatous hyperplasia of ciliary body epithelium was reported in which malignant melanoma of ciliary body was suspected. Partial resection for histopathology was performed in conjunction with cataract extraction, anterior resection and photocoagulation. Histopathology of the tumor identified as pseudoadenomatous hyperplasia of ciliary body epithelium. Partial resection of ciliary body tumor may be an alternative method for its differential diagnosis rather than enucleation and iridocyclectomy.


Enantioselective synthesis of putative lipiarmycin aglycon related to fidaxomicin/tiacumicin B.
An enantioselective synthesis of a putative lipiarmycin aglycon was accomplished and features: 1) Brown's enantioselective alkoxyallylboration and allylation of aldehydes, 2) chain elongation by iterative Horner-Wadsworth-Emmons olefination, 3) Evans' aldol reaction and 4) an ene-diene ring-closing metathesis. A neighboring-group-assisted chemoselective reductive desilylation was uncovered in this study and was instrumental to the realization of the present synthesis.


Post-heparin serum lecithinase in man and its positional specificity.
Lecithinase activity in post-heparin serum has been demonstrated. Phosphatidyl choline (PC) can be degraded to lysophosphatidyl choline and fatty acids at a rate of more than 1 micromole/hr per ml of serum in an incubation system containing PC, 0.1 M glycine-NaOH buffer (pH 9.6), and deoxycholate. This activity cannot be found in serum obtained prior to the injection of heparin. Post-heparin serum lecithinase can be distinguished from the heat-stable pancreatic lecithinase by the markedly different effects of heat, paraoxon, and EDTA, and from serum lecithin:cholesterol acyltransferase by the differential effect of p-hydroxymercuribenzoate. In contrast to the acyltransferase and to pancreatic lecithinase, which are active at the beta (C-2) position of lecithin, post-heparin serum lecithinase is active at alpha' (C-1) position.


The Hsp110 molecular chaperone stabilizes apolipoprotein B from endoplasmic reticulum-associated degradation (ERAD).
Apolipoprotein B (apoB) is the most abundant protein in low density lipoproteins and plays key roles in cholesterol homeostasis. The co-translational degradation of apoB is controlled by fatty acid levels in the endoplasmic reticulum (ER) and is mediated by the proteasome. To define the mechanism of apoB degradation, we employed a cell-free system in which proteasome-dependent degradation is recapitulated with yeast cytosol, and we developed an apoB yeast expression system. We discovered that a yeast Hsp110, Sse1p, associates with and stabilizes apoB, which contrasts with data indicating that select Hsp70s and Hsp90s facilitate apoB degradation. However, the Ssb Hsp70 chaperones have no effect on apoB turnover. To determine whether our results are relevant in mammalian cells, Hsp110 was overexpressed in hepatocytes, and enhanced apoB secretion was observed. This study indicates that chaperones within distinct complexes can play unique roles during ER-associated degradation (ERAD), establishes a role for Sse1/Hsp110 in ERAD, and identifies Hsp110 as a target to lower cholesterol.


Proteomic analysis in the Dufour's gland of Africanized Apis mellifera workers (Hymenoptera: Apidae).
The colony of eusocial bee Apis mellifera has a reproductive queen and sterile workers performing tasks such as brood care and foraging. Chemical communication plays a crucial role in the maintenance of sociability in bees with many compounds released by the exocrine glands. The Dufour's gland is a non-paired gland associated with the sting apparatus with important functions in the communication between members of the colony, releasing volatile chemicals that influence workers roles and tasks. However, the protein content in this gland is not well studied. This study identified differentially expressed proteins in the Dufour's glands of nurse and forager workers of A. mellifera through 2D-gel electrophoresis and mass spectrometry. A total of 131 spots showed different expression between nurse and forager bees, and 28 proteins were identified. The identified proteins were categorized into different functions groups including protein, carbohydrate, energy and lipid metabolisms, cytoskeleton-associated proteins, detoxification, homeostasis, cell communication, constitutive and allergen. This study provides new insights of the protein content in the Dufour's gland contributing to a more complete understanding of the biological functions of this gland in honeybees.


Solution NMR structure and X-ray absorption analysis of the C-terminal zinc-binding domain of the SecA ATPase.
The solution NMR structure of a 22-residue Zn(2+)-binding domain (ZBD) from Esherichia coli preprotein translocase subunit SecA is presented. In conjunction with X-ray absorption analysis, the NMR structure shows that three cysteines and a histidine in the sequence CXCXSGX(8)CH assume a tetrahedral arrangement around the Zn(2+) atom, with an average Zn(2+)-S bond distance of 2.30 A and a Zn(2+)-N bond distance of 2.03 A. The NMR structure shows that ND1 of His20 binds to the Zn(2+) atom. The ND1-Zn(2+) bond is somewhat strained: it makes an angle of approximately 17 degrees with the plane of the ring, and it also shows a significant "in-plane" distortion of 13 degrees. A comprehensive sequence alignment of the SecA-ZBD from many different organisms shows that, along with the four Zn(2+) ligands, there is a serine residue (Ser12) that is completely conserved. The NMR structure indicates that the side chain of this serine residue forms a strong hydrogen bond with the thiolate of the third cysteine residue (Cys19); therefore, the conserved serine appears to have a critical role in the structure. SecB, an export-specific chaperone, is the only known binding partner for the SecA-ZBD. A phylogenetic analysis using 86 microbial genomes shows that 59 of the organisms carry SecA with a ZBD, but only 31 of these organisms also possess a gene for SecB, indicating that there may be uncharacterized binding partners for the SecA-ZBD.


Nitrosation of sugar oximes: preparation of 2-glycosyl-1-hydroxydiazene-2-oxides.
Oximes of glucose, xylose, lactose, fructose, and mannose have been prepared. Nitrosation of the oximes of glucose, xylose, and lactose with NaNO2/HCl afforded 2-(beta-glycopyranosyl)-1-hydroxydiazene-2-oxides, which were isolated as salts 13, 22, and 28. Nitrosation of fructose oxime 29 furnished fructose, whereas nitrosation of mannose oxime 30 with NaNO2/HCl afforded the 1-hydroxy-2-(beta-D-mannopyranosyl)diazene-2-oxide 32, from which the p-anisidinium salt 31 and the sodium salt 33 were prepared. However, nitrosation of 30 with isopentyl nitrite in aqueous solutions of CsOH or KOH resulted in the formation of the 2-(alpha-D-mannofuranosyl)-1-hydroxydiazene-2-oxide salts 34 and 35, respectively. Methylation of the ammonium 2-(beta-D-glucopyranosyl)-1-hydroxydiazene-2-oxide 13 yielded the 1-methoxy compound, which was benzoylated to afford the tetra-O-benzoate 14a, the structure of which was confirmed by X-ray diffraction analysis. From the glucose O-methyloximes 15 and 16 the N-methoxy-N-nitroso-2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylamine 18 was prepared. The structure of this compound was confirmed by X-ray diffraction analysis. Treatment of acetobromoglucose with cupferron furnished the 1-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-2-phenyldiazene-2-oxide 20.


Thyroid carcinoma at King Edward VIII Hospital, Durban, South Africa.
Western literature depicts papillary carcinoma as the most common thyroid malignancy followed by follicular carcinoma. To assess the clinical pattern of thyroid carcinoma among African and Indian patients. King Edward VIII Hospital, Durban, South Africa. A retrospective study. One hundred patients with thyroid carcinoma treated at a tertiary teaching hospital between 1990 and 1997. Seventy seven patients were Africans and 23 were Indians. The male to female ratio was 1:6. Ninety eight patients presented with goitre with or without regional lymph node involvement or distant disease. The duration of symptoms ranged from one to 360 months. The mean age at presentation was 48.6 +/- 16.0 years. Follicular carcinoma was the most common malignancy among African patients (68%), followed by papillary carcinoma (16%), anaplastic carcinoma (13%) and medullary carcinoma (2.6%). Papillary carcinoma was the most common malignancy among Indian patients (57%) followed by follicular carcinoma and medullary carcinoma. There was no anaplastic carcinoma among Indian patients. Fifty five patients underwent lobectomy with 32 undergoing subsequent completion thyroidectomy. Nine patients had near total thyroidectomy, 27 were offered total thyroidectomy as primary surgery and eight had biopsy only. The in-hospital mortality was 8%. Recurrence rate was 8%. Most patients present long after the development of symptoms. Follicular carcinoma is the most common thyroid malignancy among Africans. Further studies are required to explain this phenomenon.


A factor that can yield to eating attitude disorders in university students: Self-esteem.
To determine prevalence of eating attitude disorder (EAD) and the effect of self-esteem on EAD in female university students. Study Design: In this cross-sectional study, female university students were included. The dependent variable was EAD determined by Eating Attitude Test-40. Socio-demographic characteristics, body perception, obesity, self-compassion and self-esteem were independent variables. Logistic regression (LR) models have been established to determine the associated factors of EAD. p < 0.05 was considered significant. Results: EAD were found in 3.3% (n = 20) of the participants (n = 600). 44.5% had low and medium self-esteem and %13.4 were overweight (body mass index (BMI) ≥ 25.0). According to LR models, after adjusted for age, increased self-esteem score (decreased self-esteem) (OR:1.8, 95%CI:1.063-3.303) and practicing popular diet (OR:12.6, 95%CI:4.439-35.904) increased the risk of EAD significantly. Conclusion: EAD were less than expected in this group of university students. Self-esteem is an important factor affecting EAD. Students with EAD may be recommended to get psychological support as well as nutritional counseling.


Combining electrochemical nitrate reduction and anammox for treatment of nitrate-rich wastewater: A short review.
Treatment of nitrate-rich wastewater is important but challenging for the conventional biological denitrification process. Here, we propose combining the electrochemical reduction and anaerobic ammonium oxidation (anammox) processes together for treatment of nitrate-rich wastewater. This article reviews the mechanism and current research status of electrochemical reduction of nitrate to ammonium as well as the mechanism and applicability of the anammox process. This article discusses the principles, superiorities and challenges of this combined process. The feasibility of the combined process depends on the efficiency of electrochemical nitrate reduction to ammonium and the conditions in the anammox process to use the reduced ammonium as the substrate to achieve deep nitrogen removal. The article provides a feasible strategy for using the electrochemical reduction and anammox combined process to treat nitrate-rich wastewater.


Towards improved comparability of studies addressing atmospheric concentrations of semivolatile organic compounds based on their sequestration in pine needles.
Coniferous needles can be used as a passive air sampler of semivolatile organic compounds (SVOC) and an indicator of atmospheric pollution patterns and trends. There is limited information on whether different parts of the plant (e.g., foliage leaves, dwarf shoots, twig, etc.) contain different levels of SVOC. Only few studies have compared levels of SVOC surface layer of wax and to their total content in all needle tissues and what affects an uptake and distribution of SVOC. It is important to have better understanding of the extent to which sampling and sample preparation procedures affect measured levels of SVOC in pine needles and reduce comparability of data from samples processed in different ways. In the present study, we assessed an impact of various sampling and sample preparation techniques on the levels of SVOC in Pinus sylvestris needles. While the impact of various storing, washing and drying methods was not significant, presence of dwarf shoots in the sample or structural damage of needles affected the results significantly. Results show that levels of SVOC in dwarf shoots are 2-8 times higher than those in foliage leaves. Therefore, dwarf shoots must be carefully removed before foliage leaves extraction to improve comparability of results. There were different patterns in SVOC on the surface of the foliage leaves compared to the whole leaves. An uptake of these substances by the surface wax as well as their occurrence in the internal structure was of function of the physico-chemical properties of the substances (log Kow, molar weight).


Purkinje neuron physiology is altered by the inflammatory factor interleukin-6.
The cytokine interleukin-6 (IL-6) is produced by cells of the central nervous system (CNS) during a variety of neuroinflammatory states, in which it is thought to play a role in neuroprotection and/or neuropathology associated with neurological disease. In addition, CNS expression of IL-6 during non-pathological conditions may also occur, although the conditions for such IL-6 production remain elusive. Expression of IL-6 and its receptor and signal transducing elements by neurons and glia within the cerebellum implicate a role of IL-6 in modulating cerebellar function under normal conditions and in contributing to pathology and pathophysiology within the cerebellum during CNS disease states. Evidence for such a role of IL-6 comes from studies using transgenic mice that chronically express IL-6 within the CNS. These mice exhibit profound cerebellar pathology and significant alterations of Purkinje neuron electrical and synaptic activity. Additional evidence comes from in vitro studies using primary cultures of cerebellar cortex that have been chronically exposed to exogenously applied IL-6. Consistent with the IL-6 transgenic mice, chronic IL-6 treated Purkinje neurons in culture exhibit alterations of endogenous electrophysiological properties as well as changes in intracellular Ca2+ homeostasis and signaling. Despite these changes in Purkinje neuron physiology, chronic IL-6 does not affect the survival or morphology of Purkinje neurons in culture. Thus, by itself, IL-6 is able to modulate key components of cerebellar circuitry during periods of chronic expression, such as during neuroinflammation, and may be an important player in the movement disorders associated with a number of CNS disease states.


Rhabdomyosarcoma of the nasal vestibule in a child.
A case of rhabdomyosarcoma in a 2 year old girl without a pre-existing predisposing factor visited the ENT Department of Sultan Qaboos University Hospital (SQUH). Her clinical condition did not point to the diagnosis, which came as a histological surprise. The histopathology report was alveolar rhabdomyosarcoma.


Phenylephrine and norepinephrine increase blood pressure through opposing physiologic mechanisms in isoflurane-anesthetized dogs receiving acepromazine.
To elucidate the cardiovascular effects of escalating doses of phenylephrine and norepinephrine in dogs receiving acepromazine and isoflurane. 8 beagles aged 1 to 2 years (7.4 to 11.2 kg). All dogs received acepromazine 0.01 mg/kg, propofol 4 to 5 mg/kg, and isoflurane and were mechanically ventilated. Mean arterial pressure (MAP) from a femoral artery catheter and continuous electrocardiogram were recorded. Cardiac output (CO) was measured with transpulmonary thermodilution. Systemic vascular resistance (SVR), global end-diastolic volume (GEDV), and global ejection fraction (GEF) were subsequently calculated. Phenylephrine and norepinephrine were infused in random order at 0.07, 0.3, 0.7, and 1.0 μg/kg/min. All variables were measured after 15 minutes of each infusion rate. The effects of dose, agent, and their interaction on the change of each variable were evaluated with mixed-effect models. A P < .05 was used for significance. Atrial premature complexes occurred in 3 dogs during norepinephrine infusion at doses of 0.3, 0.7, and 1 μg/kg/min; no dysrhythmias were seen with phenylephrine administration. MAP increased during dose escalation (P < .0001) within each agent and did not differ between agents (P = .6). The decrease in HR was greater for phenylephrine (P < .0001). Phenylephrine decreased CO and GEF and increased GEDV and SVR (all P < .03). Norepinephrine decreased the SVR and increased CO, GEDV, and GEF (all P < .03). Our results confirm that phenylephrine increases arterial pressures mainly through vasoconstriction in acepromazine-premedicated dogs while norepinephrine, historically considered a vasopressor, does so primarily through an increase in inotropism.


[THE DIAGNOSTICS OF HEREDITARY DISORDERS OF METABOLISM OF PURINES AND PYRIMIDINES IN CHILDREN USING HIGH PERFORMANCE LIQUID CHROMATOGRAPHY OF ELECTRO-SPRAY TANDEM MASS-SPECTROMETRY].
The article presents data concerning new technique of diagnostic of diseases of metabolism of purines and pyrimidines using high performance liquid chromatography combined with electro-spray mass-spectrometry. The procedure of analysis is described in detail: from pre-analytical stage to interpretation of data of liquid chromatography mass-spectrometry, control of quality of data analysis, mass-spectrometry parameters and chromatographic conditions of analysis of purines, pyrimidines and their metabolites. The reference values are presented for purine and pyrimidine nucleosides and bases in urine of healthy individuals. The chemical structure of purines, pyrimidines and their metabolites and examples of chromato-mass-spectrograms under various hereditary disorders of metabolism of purines and pyrimidines are presented as well. The article is targeted to pediatricians of all profiles, medical geneticists and physicians of laboratory diagnostic.


[Somatic mutations of mitochondrial DNA in thyroid papillary carcinoma].
To analyze the somatic mutations in the D-loop of mtDNA and further evaluate the possibility of mitochondrial genetic instability in thyroid papillary carcinoma. Hypervariable regions ( HVR-I and HVR-II) in the D-loop of mtDNA from the specimen of 35 thyroid papillary cancers and matched lymphocytes were amplified by PCR, and then were sequenced. Comparing the sequences of tumors to those of matched lymphocytes and normal thyroid tissues, 5 somatic mutations in 2 patients (5.7%) were found. Two mutations were insertions of C in a poly-cytidine (nt303) microsatellite, and 3 at positions 73, 152 and 194 in HVR-II. In addition, of the 294 genetic variants detected, 292 were previously recorded polymorphisms, whereas 2 were new polymorphisms (nt324:C-->G, nt16092:T-->A). Mutations in the D-loop of mtDNA were found in thyroid papillary cancers, this mutation rate was lower than the reported rate of alteration in tumors of epithelial origin, and further work is required to elucidate the relationship between this mutations and the development of thyroid papillary carcinoma.


Different guidelines for imaging after first UTI in febrile infants: yield, cost, and radiation.
To evaluate the yield, economic, and radiation costs of 5 diagnostic algorithms compared with a protocol where all tests are performed (ultrasonography scan, cystography, and late technetium(99)dimercaptosuccinic acid scan) in children after the first febrile urinary tract infections. A total of 304 children, 2 to 36 months of age, who completed the diagnostic follow-up (ultrasonography, cystourethrography, and acute and late technetium(99)dimercaptosuccinic acid scans) of a randomized controlled trial (Italian Renal Infection Study 1) were eligible. The guidelines applied to this cohort in a retrospective simulation were: Melbourne Royal Children's Hospital, National Institute of Clinical Excellence (NICE), top down approach, American Academy of Pediatrics (AAP), and Italian Society of Pediatric Nephrology. Primary outcomes were the yield of abnormal tests for each diagnostic protocol; secondary outcomes were the economic and radiation costs. Vesicoureteral reflux (VUR) was identified in 66 (22%) children and a parenchymal scarring was identified in 45 (15%). For detection of VUR (47/66) and scarring (45/45), the top down approach showed the highest sensitivity (76% and 100%, respectively) but also the highest economic and radiation costs (€52 268. 624 mSv). NICE (19/66) and AAP (18/66) had the highest specificities for VUR (90%) and the Italian Society of Pediatric Nephrology had the highest specificity (20/45) for scars (86%). NICE would have been the least costly (€26 838) and AAP would have resulted in the least radiation exposure (42 mSv). There is no ideal diagnostic protocol following a first febrile urinary tract infection. An aggressive protocol has a high sensitivity for detecting VUR and scarring but carries high financial and radiation costs with questionable benefit.


[Functional capacity of the elderly: measurement by the TMIG Index of Competence].
The functional capacity of the elderly was assessed in a national representative sample of elderly community residents. A stratified multistage random sampling yielded, 2,240 eligible persons, and 80.8% of them (n = 1,810) were successfully interviewed. The respondents ranged in age from 65 to 96 years, and the average age was 72.5 years; 43.2% of them were men, and the remaining 56.8% were women. The TMIG Index of Competence, a standardized multidimensional 13-item index of competence, was used for measuring the functional capacity. The total score of the index (maximum 13 points) showed a negatively skewed leptokurtic distribution: 69.6% of the respondents scored 11 points or greater while the mean was 10.8 points. A multiple classification analysis of the total score utilizing age, gender, educational attainment, and size of community as independent variables showed significant effects of age and educational attainment; the score significantly decreased with age, and the highly educated elderly showed higher score than those with lower educational attainment. The results of this study show that the majority of the elderly living in the community are well in functional capacity though the capacity tends to decline with age. The distribution of total scores observed in this study can be considered as a national standard of distribution of functional capacity measured by the TMIG Index Competence.


For What Illnesses Do Asylum Seekers and Undocumented Migrant Workers in Israel Seek Healthcare? An Analysis of Medical Visits at a Large Urgent Care Clinic for the Uninsured in Tel Aviv.
In 2017, there were nearly 80,000 asylum seekers and undocumented migrant workers in Israel, most of whom did not have health insurance. We evaluated trends in medical visits of asylum seekers and undocumented migrant workers who presented to Terem Refugee Clinic (TRC), a large clinic in Tel Aviv available only to uninsured residents of Israel. Data were collected from electronic medical records at TRC from 2013⁻2017. Diagnoses were grouped into categories using ICD-10-equivalent diagnosis codes. We used a chi-squared test for trends to test the significance of trends 2013 to 2017. There were 99,569 medical visits from 2013 to 2017 at TRC. Visits were lowest in 2013 (11,112), and relatively stable from 2014⁻2017 (range: 19,712⁻23,172). Most visits were among adults aged 18⁻35 (41.2%) and children <2 years old (23.7%). Only 3% of visits were from patients aged >50. The percentage of infectious disease diagnoses decreased over the study period, from 9.4% of all diagnoses in adults in 2014 to 5.2% in 2017, and from 32.0% of all diagnoses in children in 2013 to 19.4% in 2017. The annual percentage of respiratory diagnoses in children and adults 18⁻35 years of age, musculoskeletal in all adults, and digestive in adults except women ≥35 years old increased. Over time, asylum seekers and undocumented migrant workers visited TRC with fewer infectious diseases diagnoses overall but more respiratory diseases, including acute respiratory infections and more musculoskeletal diseases.


Should we embed randomized controlled trials within action research: arguing from a case study of telemonitoring.
Action research (AR) and randomized controlled trials (RCTs) are usually considered to be theoretically and practically incompatible. However, we argue that their respective strengths and weaknesses can be complementary. We illustrate our argument from a recent study assessing the effect of telemonitoring on health-related quality of life, self-care, hospital use, costs and the experiences of patients, informal carers and health care professionals in two urban hospital services and one remote rural primary care service in New Zealand. Data came from authors' observations and field notes of discussions with three groups: the healthcare providers and healthcare consumers who participated in the research, and a group of 17 researchers and collaborators. The consumers had heart failure (Site A, urban), airways disease (Site B, urban), and diabetes (Site C, rural). The research ran from 2008 (project inception) until 2012 (project close-off). Researchers came from a wide range of disciplines. Both RCT and AR methods were recognised from early in the process but often worked in parallel rather than together. In retrospect, we have mapped our observed research processes to the AR cycle characteristics (creation of communicative space, democracy and participation, iterative learning and improvement, emergence, and accommodation of different ways of knowing). We describe the context, conduct and outcomes of the telemonitoring trial, framing the overall process in the language of AR. Although not fully articulated at the time, AR processes made the RCT sensitive to important context, e.g. clinical processes. They resulted in substantive changes to the design and conduct of the RCT, and to interpretation and uptake of findings, e.g. a simpler technology procurement process emerged. Creating a communicative space enabled co-design between the researcher group and collaborators from the provider participant group, and a stronger RCT design. It appears possible to enhance the utility of RCTs by explicitly embedding them in an AR framework to shape stronger RCT design. The AR process and characteristics may enable researchers to evaluate telehealth while enhancing rather than compromising the quality of an RCT, where research results are returned to practice as part of the research process. Australian New Zealand Clinical Trials Registry, reference ACTRN12610000269033 .


Implicit and explicit self-construals in Chinese-heritage and Italian nonimmigrant early adolescents: Associations with self-esteem and prosocial behavior.
The current study examined levels of implicit and explicit independent and interdependent self-construals (SCs) in early adolescents with and without a migration background in Italy and assessed whether SCs were linked to youths' positive adjustment in terms of self-esteem and prosocial behavior. Chinese early adolescents of immigrant background (n = 123) and Italian mainstreamers (n = 187) aged between 11 and 13 years participated in the Semantic Misattribution Procedure and completed a set of questionnaires. Results indicated that at the implicit level, Chinese-origin youths reported higher interdependence than their Italian nonimmigrant peers, whereas at the explicit level, Italian youths scored higher on independence than their Chinese counterparts. In both ethnocultural groups, independent SC (implicit and explicit) was positively related to self-esteem, whereas interdependent SC (implicit and explicit) was positively linked to prosocial behavior. Findings underscore the usefulness of integrating implicit and explicit measures to evaluate early adolescents' SCs in multicultural contexts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Pituitary radiographic abnormalities and clinical correlates of hypogonadism in elderly males presenting with erectile dysfunction.
The prevalence of erectile dysfunction rises rapidly with age and is a frequent complaint presented in clinical practice. Although the etiology of erectile dysfunction is multifactorial, 10-20% of evaluations demonstrate testosterone deficiency. Testosterone deficiency due to secondary hypogonadism increases with age. Despite a higher prevalence of secondary hypogonadism in the elderly, there are no studies addressing hypothalamic-pituitary structural abnormalities in elderly impotent men with testosterone deficiency. We retrospectively reviewed the records of all elderly men who presented for general outpatient evaluation of erectile dysfunction from 1996 to 1999. To obtain a cohort control population, the records of 300 patients without erectile dysfunction were also reviewed. Amongst the erectile dysfunction patients, 225 were found to be testosterone deficient (testosterone < 300 ng/dl). Of these patients, 29 were additionally diagnosed with secondary hypogonadism based on a luteinizing hormone (LH) < 13 mIU/ml. Magnetic resonance imaging (MRI) or computed tomography (CT) imaging was available and reviewed in all patients diagnosed with secondary hypogonadism. Ten per cent of these patients had hypothalamic-pituitary imaging abnormalities. The prevalence of pituitary tumors within our population was not significantly elevated compared to the previous general population studies. Small-vessel white matter disease, hyperlipidemia and history of compression fractures were significantly increased in both univariate and multivariate analysis in the erectile dysfunction group compared with the control cohort. This study does not suggest that the use of hypothalamic-pituitary imaging in the evaluation of impotence in elderly men, in the absence of clinical characteristics of other hormonal loss or sella compression symptoms, will increase diagnosis of structural hypothalamic-pituitary abnormalities over that of the general population. However, the yield may increase with very low testosterone levels. These data suggest that there is an increase in ischemic white matter disease in elderly men with hypogonadism that may reflect microvascular injury to the hypothalamic-pituitary. Furthermore, these data confirm that low testosterone is associated with hyperlipidemia in the elderly. Future studies are required to assess the role of hypogonadism and hyperlipidemia, and to determine if treatment of the hormone deficiency improves the lipid profile.


Eye motility and auditory brainstem response dysfunction after whiplash injury.
The aim of this study was to identify the prevalence of brain/brainstem dysfunction after acute whiplash trauma (grades II and III according to the Quebec Task Force Classification on whiplash-associated disorders) and to investigate a possible correlation between the development of chronic symptoms and objective findings from auditory brainstem response (ABR) and eye motility tests. We used ABR and oculomotor tests and a thorough clinical, subjective and psychological evaluation in a sample of prospective whiplash trauma patients who were followed up for 2 years after the trauma. The initial test results did not reveal any prognostic clinical signs for the tested group as a whole, but we could discriminate some patients with clinical symptoms and signs paired with pathologic test results. Over time, some patients normalized clinically and their test results improved while others deteriorated clinically and their test results were worse at the 2-year investigation. Our findings of moderate derangements in the tests could be the effects of pain and/or changed cervical afferent activity at the brain/brainstem level, while eye motility dysfunction, in addition to pathological neuro-otological findings in a small proportion of the patients with severe symptoms, could be explained by lesions to the brain/brainstem.


[A Case of Pseudopancreatic Cyst Development during Bevacizumab plus Paclitaxel Therapy for Pancreatic Metastasis of Breast Cancer].
A 70s woman with pancreatic metastases of HER2-negative breast cancer was being treated with bevacizumab plus paclitaxel. Tumor markers decreased after treatment initiation. After 8 months of treatment, the patient developed abdominal pain and distention, along with loss of appetite. Contrast-enhanced abdominal CT scan images showed the presence of a large 25 cm pseudopancreatic cyst and disappearance of the pancreatic metastatic lesions. Endoscopic ultrasound-guided cystogastrostomy was performed and an AXIOS stent was placed in the lower part of the gastric body. Subsequently, the cyst disappeared and her abdominal symptoms improved. The patient was able to resume treatment with other drugs and did not experience any recurrence of pancreatitis. Four months later, the AXIOS stent was removed. Bevacizumab plus paclitaxel is reportedly effective against HER2-negative metastatic breast cancer. Bevacizumab is a molecular targeted therapy against vascular endothelial growth factor, and the mechanism of its antitumor effect and complications are different from those of conventional drugs. Paclitaxel has also been reported to cause pancreatitis in rare cases. In this case, the mechanism of response to bevacizumab plus paclitaxel for metastatic pancreatic lesions or the development of drug-induced pancreatitis was considered to be the cause of pseudopancreatic cyst formation.


Rapid evaluation and screening of interfacial reactions on self-assembled monolayers.
This paper reports 16 chemical reactions for elaborating the structures of self-assembled monolayers (SAMs) of alkanethiolates on gold. This work takes advantage of matrix-assisted laser desorption/ionization and time-of-flight mass spectrometry (MALDI-TOF MS) to rapidly characterize the products and yields of reactions that occur with molecules attached to monolayers. The paper also describes a method for screening reaction conditions, wherein monolayers are treated with an array of reactants and mass spectrometry is used to identify those regions that undergo reactions to give new, and unanticipated, products in high yield. These examples serve to increase the collection of reactions that can be used to elaborate the structures, and therefore the properties, of self-assembled monolayers of alkanethiolates on gold and to introduce label-free methods for screening interfacial reactions.


Personalized Medicine in Allergic Asthma: At the Crossroads of Allergen Immunotherapy and "Biologicals".
Major allergic disease can be viewed as clinical syndromes rather than discrete disease entities. Emerging evidence indicates that allergic asthma includes several disease phenotypes. Immunological deviation toward high T helper cell type 2 cytokine levels has been demonstrated for a subgroup of pediatric asthma patients, and now, several novel monoclonal antibodies have been approved for treatment of this subgroup as a stratified approach of "personalized" medicine in allergy. Introduction of component-based IgE testing before allergen immunotherapy (AIT), i.e., testing for IgE cross-reactivity before initiation of AIT, has also brought stratified medicine into allergy therapy. Improved responder criteria, which identify treatment-responders previous to therapy, might foster this stratification and even individualized AIT might have an impact for tailor-made therapy in the future. Furthermore, combining antibody-based treatment with AIT could help to establish more rapid AIT protocols even for allergens with a high risk of anaphylactic reactions. Efforts to advance such "personalized" medicine in pediatric allergy might be challenged by several issues including high costs for the health-care system, increasing complexity of allergy therapy, the need for physician allergy expertise, and furthermore ethical considerations and data safety issues.


Transcriptome analysis of aging mouse meibomian glands.
Dry eye disease is a common condition associated with age-related meibomian gland dysfunction (ARMGD). We have previously shown that ARMGD occurs in old mice, similar to that observed in human patients with MGD. To begin to understand the mechanism underlying ARMGD, we generated transcriptome profiles of eyelids excised from young and old mice of both sexes. Male and female C57BL/6 mice were euthanized at ages of 3 months or 2 years and their lower eyelids removed, the conjunctival epithelium scrapped off, and the tarsal plate, containing the meibomian glands, dissected from the overlying muscle and lid epidermis. RNA was isolated, enriched, and transcribed into cDNA and processed to generate four non-stranded libraries with distinct bar codes on each adaptor. The libraries were then sequenced and mapped to the mm10 reference genome, and expression results were gathered as reads per length of transcript in kilobases per million mapped reads (RPKM) values. Differential gene expression analyses were performed using CyberT. Approximately 55 million reads were generated from each library. Expression data indicated that about 15,000 genes were expressed in these tissues. Of the genes that showed more than twofold significant differences in either young or old tissue, 698 were identified as differentially expressed. According to the Gene Ontology (GO) analysis, the cellular, developmental, and metabolic processes were found to be highly represented with Wnt function noted to be altered in the aging mouse. The RNA sequencing data identified several signaling pathways, including fibroblast growth factor (FGF) and Wnt that were altered in the meibomian glands of aging mice.


Essential Role of Growth Hormone and IGF-1 in Therapeutic Effect of Ghrelin in the Course of Acetic Acid-Induced Colitis.
Previous studies have shown that ghrelin exhibits a protective and therapeutic effect in the gut. The aim of the present study was to examine whether administration of ghrelin affects the course of acetic acid-induced colitis and to determine what is the role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in this effect. In sham-operated or hypophysectomized male Wistar rats, colitis was induced by enema with 1 mL of 3% solution of acetic acid. Saline or ghrelin (given at the dose of 8 nmol/kg/dose) was administered intraperitoneally twice a day. Seven days after colitis induction, rats were anesthetized and the severity of the colitis was assessed. Treatment with ghrelin reduced the area of colonic mucosa damage in pituitary-intact rat. This effect was associated with increase in serum levels of GH and IGF-1. Moreover, administration of ghrelin improved blood flow in colonic mucosa and mucosal cell proliferation, as well as reduced mucosal concentration of proinflammatory interleukin-1β (IL-1β) and activity of myeloperoxidase. Hypophysectomy reduced serum levels of GH and IGF-1 and increased the area of colonic damage in rats with colitis. These effects were associated with additional reduction in mucosal blood follow and DNA synthesis when compared to pituitary-intact rats. Mucosal concentration of IL-1β and mucosal activity of myeloperoxidase were maximally increased. Moreover, in hypophysectomized rats, administration of ghrelin failed to affect serum levels of GH or IGF-1, as well as the healing rate of colitis, mucosal cell proliferation, and mucosal concentration of IL-1β, or activity of myeloperoxidase. We conclude that administration of ghrelin accelerates the healing of the acetic acid-induced colitis. Therapeutic effect of ghrelin in experimental colitis is mainly mediated by the release of endogenous growth hormone and IGF-1.


Method for controlling temperature sensitivity of the fiber intermodal sensor and its application in the torsion sensor.
Temperature crosstalk has always been a critical problem for fiber intermodal sensors. In this work, we have proposed a novel method based on the special temperature response of photosensitive fiber to control the temperature sensitivity of the fiber intermodal sensor. The control of temperature sensitivity has been realized via adjusting the proportion of photosensitive fiber to single-mode fiber in the sensing part. The temperature sensitivity as high as -192 pm/°C, and as low as -2.6 pm/°C can be obtained, satisfying the demand in both research and application. The torsion sensor is taken as an example to illustrate feasibility of this method, showing no evident interference in the measurement of torsion parameters. The proposed method outstrips the conventional one by simple structure, facile manufacture, multiple use and low cost, which brings great promise for further employment in laboratory and industry.


Perceptual information and attentional constraints in visual search of collision events.
This study examined the detection of collision events when multiple moving objects were present in the scene. Observers were presented with displays simulating a 3-D environment with multiple moving objects. The authors examined the ability of observers to detect collisions using a signal-detection paradigm and a visual search paradigm. The results indicated that, overall, observers were quite accurate at detecting collisions. Observers used both expansion information and static position to detect collisions, with expansion information being the more important source. Singleton search conditions were not processed in parallel, and conjunction search conditions had poorer performance than singleton search conditions. In addition, reaction times were greater for target-present trials as compared with target-absent trials. The results are interpreted in terms of 4 visual search hypotheses for collision detection when multiple moving objects are present.


Quantum-to-Classical Crossover in Many-Body Chaos and Scrambling from Relaxation in a Glass.
Chaotic quantum systems with Lyapunov exponent λ_{L} obey an upper bound λ_{L}≤2πk_{B}T/ℏ at temperature T, implying a divergence of the bound in the classical limit ℏ→0. Following this trend, does a quantum system necessarily become "more chaotic" when quantum fluctuations are reduced? Moreover, how do symmetry breaking and associated nontrivial dynamics influence the interplay of quantum mechanics and chaos? We explore these questions by computing λ_{L}(ℏ,T) in the quantum spherical p-spin glass model, where ℏ can be continuously varied. We find that quantum fluctuations, in general, make paramagnetic phase less and the replica symmetry-broken spin glass phase more chaotic. We show that the approach to the classical limit could be nontrivial, with nonmonotonic dependence of λ_{L} on ℏ close to the dynamical glass transition temperature T_{d}. Our results in the classical limit (ℏ→0) naturally describe chaos in supercooled liquid in structural glasses. We find a maximum in λ_{L}(T) substantially above T_{d}, concomitant with the crossover from simple to slow glassy relaxation. We further show that λ_{L}∼T^{α}, with the exponent α varying between 2 and 1 from quantum to classical limit, at low temperatures in the spin glass phase.


Synthesis of 11-hydroxyl O-methylsterigmatocystin and the role of a cytochrome P-450 in the final step of aflatoxin biosynthesis.
The major skeletal rearrangements (anthraquinone --> xanthone --> coumarin) that occur in the complex biosynthesis of aflatoxin B(1) are mediated by cytochromes P-450. Previous experiments have suggested that two successive monooxygenase reactions are required to convert the xanthone O-methylsterigmatocystin (OMST) to aflatoxin, a process we demonstrate is mediated by a single P-450, OrdA, in Aspergillus parasiticus in accord with findings in A. flavus. The first oxidative cycle is proposed to result in the formation of 11-hydroxy O-methylsterigmatocystin (HOMST), while the second entails aryl ring cleavage, demethylation, dehydration, decarboxylation, and rearrangement to give aflatoxin - a remarkable sequence of transformations. To test this hypothesis, HOMST has been synthesized by an alkylnitrilium variant of the Houben-Hoesch reaction. The troublesome xanthone carbonyl was protected as a butylene to allow further elaboration of the molecule, and then the product xanthone was restored in a uniquely facile peracid deprotection. Methods were devised to construct the sensitive dihydrobisfuran and to maintain the oxidation state of the partially methylated hydroquinone. Expression of ordA in a yeast membrane preparation enabled the intermediacy of HOMST both to be detected in the conversion of OMST to aflatoxin and to be established directly in the biosynthesis of the mycotoxin. Having secured the role of HOMST in aflatoxin formation, the mechanism of the second oxidative cycle of this P-450 is considered.


Rad and Rem are non-canonical G-proteins with respect to the regulatory role of guanine nucleotide binding in Ca(V)1.2 channel regulation.
Rad and Rem are Ras-like G-proteins linked to diverse cardiovascular functions and pathophysiology. Understanding how Rad and Rem are regulated is important for deepened insights into their pathophysiological roles. As in other Ras-like G-proteins, Rad and Rem contain a conserved guanine-nucleotide binding domain (G-domain). Canonically, G-domains are key control modules, functioning as nucleotide-regulated switches of G-protein activity. Whether Rad and Rem G-domains conform to this canonical paradigm is ambiguous. Here, we used multiple functional measurements in HEK293 cells and cardiomyocytes (Ca(V)1.2 currents, Ca(2+) transients, Ca(V)β binding) as biosensors to probe the role of the G-domain in regulation of Rad and Rem function. We utilized Rad(S105N) and Rem(T94N), which are the cognate mutants to Ras(S17N), a dominant-negative variant of Ras that displays decreased nucleotide binding affinity. In HEK293 cells, over-expression of either Rad(S105N) or Rem(T94N) strongly inhibited reconstituted Ca(V)1.2 currents to the same extent as their wild-type (wt) counterparts, contrasting with reports that Rad(S105N) is functionally inert in HEK293 cells. Adenovirus-mediated expression of either wt Rad or Rad(S105N) in cardiomyocytes dramatically blocked L-type calcium current (I(Ca,L)) and inhibited Ca(2+)-induced Ca(2+) release, contradicting reports that Rad(S105N) acts as a dominant negative in heart. By contrast, Rem(T94N) was significantly less effective than wt Rem at inhibiting I(Ca,L) and Ca(2+) transients in cardiomyocytes. FRET analyses in cardiomyocytes revealed that both Rad(S105N) and Rem(T94N) had moderately reduced binding affinity for Ca(V)βs relative to their wt counterparts. The results indicate Rad and Rem are non-canonical G-proteins with respect to the regulatory role of their G-domain in Ca(V)1.2 regulation.


C9 and factor B as acute phase proteins and their diagnostic and prognostic value in disease.
Some components of complement, such as C3, C9 and factor B, behave as acute phase reactants and their serum levels increase significantly in the course of inflammation. The diagnostic and prognostic significance of estimating the serum levels of C9 and factor B was evaluated in patients with Behçet's syndrome, recurrent oral ulceration and Crohn's disease, and the results were compared with those of measuring other acute phase reactants, such as C-reactive protein or alpha 1-antitrypsin. Longitudinal studies in these patients show a clear correlation between clinical indexes of the disease and levels of C9 and factor B. These findings, and experimental studies in monkeys, suggest that inflammation variously affects the synthesis of the acute phase reactants and that they play different roles as mediators of cellular damage.


Cloning and sequence analysis of cDNAs for neurohypophysial hormones vasotocin and mesotocin for the hypothalamus of toad, Bufo japonicus.
The primary structures of the precursors of neurohypophysial hormones vasotocin (VT) and mesotocin (MT) in the hypothalamus of the toad Bufo japonicus were determined by analyzing the nucleotide sequences of the cloned cDNAs encoding them. The MT precursor consists of 125 amino acid residues containing a signal peptide followed directly by MT, which in turn is connected to the MT neurophysin by Gly-Lys-Arg, a processing and carboxyl-terminal amidation signal. In contrast, the VT precursor includes a glycoprotein of 36 amino acids following the VT neurophysin. Except for glycoprotein, the structures of MT and VT precursors are quite similar. RNA transfer blotting analysis showed that both MT and VT mRNAs are present in the brain but not in the liver, ovaries, and testes of the toad. The sequences and the structural organizations of the MT and VT precursors are highly homologous to those of their mammalian counterparts, oxytocin and arginine vasopressin precursors, respectively. This fact suggests that, in the evolutionary pathway of neurohypophysial hormones, VT is the ancestor molecule of vasopressin, while MT is that of oxytocin.


Lesbians still face job discrimination.
This article examines continued discrimination against lesbians in the workplace. A number of cases from various jurisdictions in the United States are highlighted. The paper studies two common forms of discrimination: denial of employment benefits to same sex partners, and sexual harassment. On the first front, the case law suggests that health insurance coverage for one's partner is becoming the norm. On the question of sexual harassment in the workplace, the case law did not provide protection for lesbians. Finally, U.S. employment policies related to sexual orientation are contrasted with those in Israel, which provides much greater protection from discrimination.


Prediction of urinary continence following radical prostatectomy.
The aim of this study was to assess the incidence of incontinence after radical prostatectomy and to identify the various factors that can predict urinary continence after radical prostatectomy. Urinary continence following a radical prostatectomy was evaluated in 175 consecutive patients who underwent surgery. Immediately after catheter withdrawal, on the 15th postoperative day, 66% of the patients were incontinent. Varying degrees of incontinence persisted in 53% of the cohort at 1 month postoperatively. Thirty-three, 12, 8 and 2% of the patients remained incontinent at respectively 3, 6, 9 and 12 months of follow-up. A number of possible pre- and peroperative factors which might predict the continence status were examined are related to it at subsequent intervals after the surgical intervention. Preservation of the neurovascular bundles, prior transurethral resection of the prostate, preoperative micturition disorders and age were significant contributors in the prediction of urinary incontinence after radical prostatectomy.


[Systematic study of Saccharomyces: oxidases and vitamin requirements].
A study of the genus Saccharomyces by new biocharacters demonstrates indirectly the genotype of each species; intracellular osidases (lactose - maltose -cellobiase - melibiase - invertase - trehalase) and vitamin requirements (biotin-folic acid-inositol-niacine-pantothénate-para-aminobenzoic acid-pyridozine-thiamine) reveal some phylogenetic links between the species. It appears that Van der Walt's group I is very homogeneous and must be restricted to only 7 species. The torulospora group seems very similar to the genus Debaryomyces when vitamin needs and osidases are considered; the relations between the 2 groups are discussed. When other biocharacters are studied (nitrite reductase-immunological properties, etc. ...) the value in the GC content (4-5% lower in Debaryomyces) will be established. These results confirm that intracellular oxidases and vitamin needs are very valuable tools for systematic criteria.


Mother- and father-reported reactions to children's negative emotions: relations to young children's emotional understanding and friendship quality.
Mother- and father-reported reactions to children's negative emotions were examined as correlates of emotional understanding (Study 1, N = 55, 5- to 6-year-olds) and friendship quality (Study 2, N = 49, 3- to 5-year-olds). Mothers' and fathers' supportive reactions together contributed to greater child-friend coordinated play during a sharing task. Further, when one parent reported low support, greater support by the other parent was related to better understanding of emotions and less intense conflict with friends (for boys only). When one parent reported high support, however, greater support by the other parent was associated with less optimal functioning on these outcomes. Results partially support the notion that children benefit when parents differ in their reactions to children's emotions.


ENTVis: A Visual Analytic Tool for Entropy-Based Network Traffic Anomaly Detection.
Entropy-based traffic metrics have received substantial attention in network traffic anomaly detection because entropy can provide fine-grained metrics of traffic distribution characteristics. However, some practical issues--such as ambiguity, lack of detailed distribution information, and a large number of false positives--affect the application of entropy-based traffic anomaly detection. In this work, we introduce a visual analytic tool called ENTVis to help users understand entropy-based traffic metrics and achieve accurate traffic anomaly detection. ENTVis provides three coordinated views and rich interactions to support a coherent visual analysis on multiple perspectives: the timeline group view for perceiving situations and finding hints of anomalies, the Radviz view for clustering similar anomalies in a period, and the matrix view for understanding traffic distributions and diagnosing anomalies in detail. Several case studies have been performed to verify the usability and effectiveness of our method. A further evaluation was conducted via expert review.


Age Differences in Motivated Cognition: A Meta-Analysis.
The goal of this preregistered study was to synthesize empirical findings on age differences in motivated cognition using a meta-analytic approach, with a focus on the domains of cognitive control and episodic memory. A systematic search of articles published before July 2022 yielded 27 studies of cognitive control (N = 1,908) and 73 studies of memory (N = 5,837). Studies had to include healthy younger and older adults, a within-subjects or between-subjects comparison of motivation (high vs low), and a measure of cognitive control or memory. The Age × Motivation effect size was meta-analyzed using random-effects models, and moderators were examined using meta-regressions and subgroup analyses. Overall, the Age × Motivation interaction was not significant in either cognitive domain, but the effect sizes in both domains were significantly heterogeneous, indicating a possible role of moderating factors in accounting for effect size differences. Moderator analyses revealed significant moderation by incentive type for episodic memory, but not for cognitive control. Older adults' memory was more sensitive to socioemotional rewards, whereas younger adults' memory was more sensitive to financial gains. Findings are discussed with reference to the dopamine hypothesis of cognitive aging and to life-span theories of motivational orientation. None of these theories is fully supported by the meta-analysis findings, highlighting the need for an integration of neurobiological, cognitive process, and life-span-motivational perspectives.


Nima- and Aurora-related kinases of malaria parasites.
Completion of the life cycle of malaria parasite requires a succession of developmental stages which vary greatly with respect to proliferation status, implying a tightly regulated control of the parasite's cell cycle, which remains to be understood at the molecular level. Progression of the eukaryotic cell cycle is controlled by members of mitotic kinase of the families CDK (cyclin-dependent kinases), Aurora, Polo and NIMA. Plasmodium parasites possess cyclin-dependent protein kinases and cyclins, which strongly suggests that some of the principles underlying cell cycle control in higher eukaryotes also operate in this organism. However, atypical features of Plasmodium cell cycle organization and important divergences in the composition of the cell cycle machinery suggest the existence of regulatory mechanisms that are at variance with those of higher eukaryotes. This review focuses on several recently described Plasmodium protein kinases related to the NIMA and Aurora kinase families and discusses their functional involvement in parasite's biology. Given their demonstrated essential roles in the erythrocytic asexual cycle and/or sexual stages, these enzymes represent novel potential drug targets for antimalarial intervention aiming at inhibiting parasite replication and/or blocking transmission of the disease. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).


Investigation of the efficacy of the change ratio of brain natriuretic peptide for predicting the cardiac effects of chemoradiotherapy on esophageal cancer.
The aim of this study was to investigate the effectiveness of brain natriuretic peptide (BNP) as a predictor of radiological effects on the heart. A total of 41 patients with esophageal cancer who underwent chemoradiotherapy (CRT) were retrospectively investigated. The BNP levels were measured on the first day of CRT (pre-CRT) and the last day of CRT (post-CRT), and the median concentration of BNP and dosimetric parameters of the heart were calculated. The change ratio of BNP was calculated as follows: [(BNP post-CRT) - (BNP pre-CRT)]/(BNP pre-CRT). The comparison of BNP pre-CRT with post-CRT was performed using a Wilcoxon signed-rank test. The relationship between dosimetric parameters and change ratio was analyzed using Spearman's correlation coefficient. The median levels of BNP of pre-CRT and post-CRT were 10 and 22 pg/ml, respectively, and the difference was statistically significant (P<0.0001). Significant correlations (all P<0.05) were observed between the change ratio and mean dose, V5, V10, V20, and V30. Of the cohort, 14 patients developed acute-to-subacute cardiac events, such as pericardial effusion, cardiomegaly, acute exacerbation of chronic heart failure, and a decreased ejection fraction. The change ratios of BNP, V5, V10, V20, and V30 were significantly higher in patients who experienced cardiac events compared with those who did not. The results of this study showed that BNP measurement, particularly the change ratio of BNP pre- and post-CRT, may be a useful cardiac event predictor in addition to dosimetric parameters.


Selection of auxotrophic bacterial mutants by tritium-labeled thymidine.
A method is proposed for the efficient isolation of auxotrophic mutants of cells of diverse origin by the use of radioactive materials. An example is described in which mutants of Escherichia coli B were selected by growing irradiated cells in the presence of tritium-labeled thymidine.


Reactions of thiosemicarbazones derived from beta-keto amides and beta-keto esters with Zn(II) and Cd(II) acetates: influence of metal, substitution, reagent ratio and temperature on metal-induced cyclization.
Zinc(II) and cadmium(II) acetates were reacted in methanol under various experimental conditions with thiosemicarbazones derived from beta-keto amides or beta-keto esters (HTSC). Some of these reactions afforded thiosemicarbazonate complexes [M(TSC)2] with IR and NMR spectra compatible with N,S-coordination, but most gave complexes [ML2], where HL is a substituted 2,5-dihydro-5-oxo-1H-pyrazole-1-carbothioamide resulting from cyclization of the HTSC. Some of these pyrazolonates and two of the HL ligands were studied by X-ray diffractometry, and their structures are discussed. Surprisingly, the reactions of zinc(II) acetate with HTSC in 1:1 mol ratio usually gave a third, previously unreported type of complex with a dideprotonated ligand, [Zn(L-H)], which was also formed when [ZnL2] and Zn(OAc)2 interacted at room temperature in 1:1 mol ratio. These L-H complexes are highly insoluble in all common solvents, which hinders their characterization but suggests that they are polymeric in nature.


The quality of free antenatal and delivery services in Northern Sierra Leone.
The number of maternal deaths in sub-Saharan Africa continues to be overwhelmingly high. In West Africa, Sierra Leone leads the list, with the highest maternal mortality ratio. In 2010, financial barriers were removed as an incentive for more women to use available antenatal, delivery and postnatal services. Few published studies have examined the quality of free antenatal services and access to emergency obstetric care in Sierra Leone. A cross-sectional survey was conducted in 2014 in all 97 peripheral health facilities and three hospitals in Bombali District, Northern Region. One hundred antenatal care providers were interviewed, 276 observations were made and 486 pregnant women were interviewed. We assessed the adequacy of antenatal and delivery services provided using national standards. The distance was calculated between each facility providing delivery services and the nearest comprehensive emergency obstetric care (CEOC) facility, and the proportion of facilities in a chiefdom within 15 km of each CEOC facility was also calculated. A thematic map was developed to show inequities. The quality of services was poor. Based on national standards, only 27% of women were examined, 2% were screened on their first antenatal visit and 47% received interventions as recommended. Although 94% of facilities provided delivery services, a minority had delivery rooms (40%), delivery kits (42%) or portable water (46%). Skilled attendants supervised 35% of deliveries, and in only 35% of these were processes adequately documented. None of the five basic emergency obstetric care facilities were fully compliant with national standards, and the central and northernmost parts of the district had the least access to comprehensive emergency obstetric care. The health sector needs to monitor the quality of antenatal interventions in addition to measuring coverage. The quality of delivery services is compromised by poor infrastructure, inadequate skilled staff, stock-outs of consumables, non-functional basic emergency obstetric care facilities, and geographic inequities in access to CEOC facilities. These findings suggest that the health sector needs to urgently investigate continuing inequities adversely influencing the uptake of these services, and explore more sustainable funding mechanisms. Without this, the country is unlikely to achieve its goal of reducing maternal deaths.


Temporal trends in craniometric estimates of admixture for a modern American sample.
Temporal trends in craniometric estimates of admixture are investigated for three U.S. populations in the FDB. Patterns of association between birth years and posterior probabilities of cluster membership are identified to assess how these proportions of admixture have changed over recent time. Demographic and genetic data correlates, patterns of morphological expression, and shifts in source populations are evaluated. Estimates of three-way admixture were obtained for 1,521 individuals of documented population, sex, and birth years that span the 20th century. Correlations were calculated between birth years and admixture proportions for members of each FDB population. Population and sex-specific admixture variation was further assessed by ANOVA and regression. Correlation analysis was used to identify, per population, which of the cranial measurements change in dimension under increased or decreased admixture. Admixture proportions differ significantly by population and change over time. No sex differences are detected. Analysis of the relationship between admixture proportions and ILDs finds that admixture drives morphological change in areas of the cranium known to vary among populations. Results agree with prior work on secular change. Findings reveal a progressive increase in White-European population admixture for the self-identified Black individuals, a recent demographic shift toward the increased representation of Hispanic individuals carrying greater Native American ancestry, and reduction in admixture for White individuals that suggest a loss of diversity over time. Changes in admixture produce tractable differences in morphological expression. Both sexes exhibit similar admixture proportions and self-identification patterns. Observed diachronic trends are corroborated by information on recent U.S. demographic change.


Quality assurance guidelines for superficial hyperthermia clinical trials : II. Technical requirements for heating devices.
Quality assurance (QA) guidelines are essential to provide uniform execution of clinical trials with uniform quality hyperthermia treatments. This document outlines the requirements for appropriate QA of all current superficial heating equipment including electromagnetic (radiative and capacitive), ultrasound, and infrared heating techniques. Detailed instructions are provided how to characterize and document the performance of these hyperthermia applicators in order to apply reproducible hyperthermia treatments of uniform high quality. Earlier documents used specific absorption rate (SAR) to define and characterize applicator performance. In these QA guidelines, temperature rise is the leading parameter for characterization of applicator performance. The intention of this approach is that characterization can be achieved with affordable equipment and easy-to-implement procedures. These characteristics are essential to establish for each individual applicator the specific maximum size and depth of tumors that can be heated adequately. The guidelines in this document are supplemented with a second set of guidelines focusing on the clinical application. Both sets of guidelines were developed by the European Society for Hyperthermic Oncology (ESHO) Technical Committee with participation of senior Society of Thermal Medicine (STM) members and members of the Atzelsberg Circle.


The Roma Population Living in Segregated Settlements in Eastern Slovakia Has a Higher Prevalence of Metabolic Syndrome, Kidney Disease, Viral Hepatitis B and E, and Some Parasitic Diseases Compared to the Majority Population.
Background: The Roma population is one of the largest marginalized population groups in Europe. The aim of our work was to summarize the morbidity of lifestyle-related diseases and infectious diseases in the Roma population living in segregated settlements. Methods: We used data from the cross-sectional study HepaMeta, in which we examined 452 Roma subjects with an average age of 34.7 ± 9.1 years, 35.2% of which were men, and 403 non-Roma subjects with an average age of 33.5 ± 7.4 years, 45.9% of which were men. We collected data by means of a questionnaire, anthropometric measures, and we analyzed blood and urine samples. Results: Roma subjects had a higher incidence of metabolic syndrome (RR: 1.478 (1.159-1.885), p < 0.0001), obesity or waist circumference >94 cm in men/80 cm in women (RR: 1.287 (1.127-1.470), p < 0.0001), and HDL-C < 1.03 mmol/L in men or <1.29 in women (RR: 2.004 (1.730-2.321), p < 0.0001) than their non-Roma counterparts. Subjects of the Roma population were more frequently diagnosed with kidney disease (RR: 1.216 (1.096-1.349), p < 0.0001), HBsAg positivity (RR: 4.468 (2.373-8.415), p < 0.0001), anti HBc IgG positivity (RR: 3.13 (2.598-4.224), p < 0.0001), and anti HEV positivity (RR: 2.972 (1.226-7.287), p < 0.0001). Serological markers of Toxoplasma gondii infection and Toxocara spp. were observed much more frequently among Roma than non-Roma subjects (RR: 1.868 (1.520-2.296), p < 0.0001, for Toxoplasma gondii; and RR: 21.812 (8.097-58.761), p < 0.0001, for Toxocara spp.). Conclusions: Poor socio-economic conditions, an unhealthy lifestyle, and barriers precluding access to healthcare are factors that affect the Roma population in settlements and lead to an increased prevalence of metabolic syndrome and its components, kidney disease, viral hepatitis B and E, and some parasitic diseases.


Interleukin 6 promoter polymorphisms in normal Han Chinese population: frequencies and effects on inflammatory markers.
Interleukin 6 (IL-6) is a cytokine involved in different physiologic and pathophysiologic processes, and circulating levels of IL-6 differ greatly between individuals, but the results have not always been concordant among diverse populations. The aim of present study was to determine the prevalence of the 3 polymorphisms (-174G/C, -597G/A, and -634C/G) in the IL-6 gene promoter region and their effects on inflammatory markers in normal Han Chinese population. A total of 232 subjects (143 men and 89 women; mean age, 51.37 ± 17.63 years; range, 22-88 years) of unrelated healthy Han Chinese in Jinangsu area (south of China) were enrolled. Genotyping of the 3 polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis and then confirmed by direct sequencing. Among the 232 individuals studied, 231 carried the GG wild type of -174G/C; only 1 carried the GC genotype. For -597G/A polymorphism, individuals all carried the GG wild type; the GA or AA genotypes were not detected. The frequencies of -634C/G genotypes CC, CG, and GG were found to be 59.48%, 37.07%, and 3.45%, respectively, the derived allele frequencies for the C and G alleles were 78.02% and 21.98%. There were no significant differences in age, sex, body mass index, or lipids parameters between the -634 CC and CG+GG genotypes. However, individuals with CC genotype showed lower levels of high-sensitivity C-reactive protein and IL-6 than those with CG+GG genotype. IL-6 -174G/C and -597G/A are rare, but -634C/G is common in Han Chinese population, and the -634G allele is associated with circulating levels of IL-6 and C-reactive protein.


Late embolization of disc occluder of a Beall mitral prosthesis with survival.
A case of arterial embolization of a Beall mitral prosthesis disc (model 104) 5 1/2 years after implantation is presented. The patient was referred to use 3 days after the onset of acute symptoms and was immediately operated upon in pulmonary edema and cardiogenic shock. The migrated disc was removed from the abdominal aorta 26 days later, showing marked signs of wear. The postoperative course was complicated and the patient made a slow recovery. It is suggested that patients with models 103 and 104 Beall mitral prostheses be followed very closely and that electric valve substitution should be considered when first signs of prosthetic attrition are noted.


Phase I study of hyperfractionated radiation therapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic cancer.
This study investigated the maximum-tolerated dose of hyperfractionated radiation therapy with protracted 5-fluorouracil (5-FU) infusion in patients with locally advanced, unresectable pancreatic cancer. Five cohorts of patients were scheduled to receive escalating doses of hyperfractionated radiation therapy (range, 45.6-64.8 Gy). All patients received two fractions of 1.2 Gy each (separated by 6 h) per day for 5 days a week, and received protracted 5-FU infusion (200 mg/m2/day) during the radiation course. The maximum-tolerated dose was defined as one dose level below the dose at which more than one third of 3-6 patients experienced dose-limiting toxicity. Twenty-nine patients were enrolled in this study. The most common toxicities were nausea/vomiting and anorexia. Although 1 patient developed bleeding from a gastric ulcer 3 months after the completion of chemoradiotherapy, the maximum-tolerated dose was not reached even at the highest dose level (level 5, 64.8 Gy). The median survival time was 12.2 months and the 1-year survival rate was 55.0%. The toxicity associated with our regimen was tolerable up to dose level 5 (64.8 Gy). We are currently conducting a phase II study of this hyperfractionated radiation therapy with protracted 5-FU infusion at a dose of 64.8 Gy.


Effects of a novel inclined-adaptive footwear on change-of-direction performance in male athletes.
Although enhancing change of direction (COD) performance is a crucial factor for improving athletic performance in many sports, few studies have explored its effective methods. This study aimed to investigate the effects of inclined-adaptive footwear (IAF) on force-time characteristics during a COD task. Thirteen male team sport athletes were randomly assigned to wear IAF or footwear without adaptive technology to perform a COD60° task at their best effort. A three-dimensional force plate was used to obtain the force-time curve and related parameters at the turning step (plant foot). IAF led to a significantly higher resultant ground reaction force (GRF), horizontal GRF, vertical GRF, and horizontal/vertical ratio during the braking phase, followed by a significantly shorter contact time and higher resultant horizontal GRF and vertical GRF during the propulsive phase. This indicated that a greater GRF output, redistributed GRF, and shorter contact time occurred with the IAF. Therefore, IAF has the potential to enhance COD performance for sports involving multi-directional footwork and contribute to the development of new functional footwear.


New eremophilenolides from Ligulariopsis shichuana.
Four new eremophilenolides, 1-4, have been isolated from the whole plant of Ligulariopsis shichuana. Their structures were elucidated by spectroscopic methods, including 2D NMR experiments. Structures of compounds 1 and 2 were unequivocally established by X-ray diffraction experiments. All of these sesquiterpenes have eremophilane skeletons with 7(11)-en-8(12) lactone units. Compounds 1 and 2 showed moderate antibacterial activities against E. coli and B. subtilis.


Mucoepidermoid carcinoma of the conjunctiva.
Mucoepidermoid carcinoma of the conjunctiva (MECa) is a rare neoplasm. It resembles squamous cell carcinoma (SCCa), clinically and histologically. Nevertheless, it is characterized by a high degree of local aggressiveness. We reviewed all cases of MECa reported in the English literature for epidemiological data, characteristics of the tumor, treatment, and outcome. We found that MECa, reported predominantly in aging males (median age 71 years), arises in the limbal and perilimbal areas. Simple excision is followed by rapid recurrence, and most tumors will require enucleation or exenteration for local control. Histological stains directed to the production of mucin are essential for the diagnosis. The recommended treatment is wide local excision. Enucleation or exenteration is recommended for tumors invading the globe or orbit.


[Nursing and quality of life in CKD].
Quality of life is one of the main targets of modern medicine. This applies specifically to people suffering from chronic diseases, who are frequently hospitalized and receive continuing care for their irreversible condition. Among chronic diseases, end-stage renal disease is extremely interesting because it can be assessed transversely in different settings but also longitudinally over time, thus allowing adequate evaluation of quality of life.


A Multiplex Human Pluripotent Stem Cell Platform Defines Molecular and Functional Subclasses of Autism-Related Genes.
Autism is a clinically heterogeneous neurodevelopmental disorder characterized by impaired social interactions, restricted interests, and repetitive behaviors. Despite significant advances in the genetics of autism, understanding how genetic changes perturb brain development and affect clinical symptoms remains elusive. Here, we present a multiplex human pluripotent stem cell (hPSC) platform, in which 30 isogenic disease lines are pooled in a single dish and differentiated into prefrontal cortex (PFC) lineages to efficiently test early-developmental hypotheses of autism. We define subgroups of autism mutations that perturb PFC neurogenesis and are correlated to abnormal WNT/βcatenin responses. Class 1 mutations (8 of 27) inhibit while class 2 mutations (5 of 27) enhance PFC neurogenesis. Remarkably, autism patient data reveal that individuals carrying subclass-specific mutations differ clinically in their corresponding language acquisition profiles. Our study provides a framework to disentangle genetic heterogeneity associated with autism and points toward converging molecular and developmental pathways of diverse autism-associated mutations.


Sugar-specific interaction of bovine brain beta-galactoside-binding lectin with endogenous gangliosides.
Sugar-specific binding of the 14 kDa beta-galactoside-binding lectin from bovine brain grey matter to mixed endogenous gangliosides was demonstrated by affinity electrophoresis and hemagglutination inhibition. Gangliosides prepared by Folch extraction, base treatment and silica gel chromatography, when incorporated in native or desialated form in polyacrylamide gel above their critical micellar concentration, arrested the mobility of the lectin during electrophoresis at pH 8.2. This effect was sugar-specific since it was reversed if lactose, but not sucrose, was present in the gel. Also, retention of the brain lectin by ganglioside and its reversal by lactose were concentration-dependent. In presence of bovine serum albumin, at pH 7.4 native and desialylated gangliosides equally inhibited agglutination of trypsinized rabbit red cells by bovine brain lectin, but not that by the alpha-galactoside-specific antibody from human serum. Results suggested the possibility of endogenous gangliosides acting as cell surface receptors in mediation of brain lectin function.


Norepinephrine modulates IL-1β-induced catabolic response of human chondrocytes.
The influence of the sympathetic nervous system (SNS) on metabolism of bone and cartilage expressing β-adrenergic receptors (AR) was suggested. Here, we investigated whether the SNS functions as a modulator of cartilage metabolism induced by interleukin-1beta (IL-1β). Human articular chondrocytes and articular cartilage were collected from patients with osteoarthritis (OA). Chondrocyte monolayer and cartilage explant culture were stimulated with IL-1β. The activity of β-ARs was modulated by an agonist, norepinephrine (NE), and antagonists, including propranolol, atenolol, nebivolol, and nadolol. The levels of β1-, β2-, and β3-AR in OA cartilage and IL-1β-treated chondrocytes were lower than normal cartilage and untreated cells. Treatment of chondrocytes with IL-1β and β-blockers, including propranolol, atenolol, nebivolol, and nadolol, for 6 h significantly upregulated IL-1β-induced expression of MMP-1, -3, and - 13, compared to chondrocytes treated with IL-1β alone, indicating that antagonism of β-AR confers catabolic signals. On the other hand, NE antagonized IL-1β-induced catabolic response. In addition, NE significantly inhibited IL-1β-induced release of glycosaminoglycan (GAG) from cartilage explant culture. In addition, β-AR activity significantly affected IL-1β-stimulated phosphorylation of JNK and ERK. These results indicate that β-AR signal is associated with cartilage metabolism. Our findings showed that β-ARs is a regulator of cartilage catabolism induced with IL-1β.


[Preliminary report on prevention of adhesion after orbital trauma by chitosan membrane].
To study the result and the mechanism of preventing postoperative adhesion after orbit trauma by chitosan membrane, and to observe the effects of chitosan membrane on optic nerve and visual function. It was a self-control trail. Ten white rabbits (twenty eyes) were adopted in this experiment. Right eye on each rabbit was used in chitosan membrane experiment group and the left eye in control group. Trauma was made between superior rectus muscle and corresponding periosteum. Chitosan membrane was implanted between trauma tissues in the experimental group. F-VEP was tested 1 day before the operation and 6 days after operation in each rabbits. Degree of adhesion was evaluated by naked eyes; inflammatory score was evaluated by pathological examination and TGF-p3 impression was evaluated by immunohistochemical studies. F-VEP examination 6 days after the operation showed that the wave amplitude of Pt1 was (9.847 +/- 2.320) mV, latency of P1 was (71.700 +/- 5.144) ms. There was no difference between pre- and post-operative data (t = 0.974, 0.228; P > 0.01). Adhesion degree evaluation showed that there were 7 eyes with 1 score, 3 eyes with 2 score in the experimental group; while there were 1 eye with 2 score, 5 eyes with 3 score, 4 eyes with 4 score in the control group. There was a statistically significant difference (T = 59.00, P < 0.01) in adhesion degree between experimental group and control group. A statistically significant difference was presented in pathologic sheet score between the experimental and control groups. There were 6 eyes with 1 score, 4 eyes with 2 score in experimental group; while 2 eyes with 1 score, 4 eyes with 2 score, 4 eyes with 3 score in the control group. Immunohistochemical study showed strong positive in all slides of the experimental group, while only weakly positive in the control group. Chitosan membrane is effective on decreasing the synthesis of collagen fibrils and preventing adhesion after the orbit trauma in the rabbits.


Differential effects of interleukin-1 alpha, tumor necrosis factor alpha, and transforming growth factor beta 1 on cell proliferation and collagen formation by cultured fat-storing cells.
Fat-storing cells (FSCs), perisinusoidal cells which normally participate in metabolism of vitamin A, have been suggested to participate in collagen synthesis in fibrotic liver. However, key mediators which regulate collagen metabolism in FSCs are yet to be elucidated. In fibroblasts, Interleukin-1 (IL-1), Tumor Necrosis Factor alpha (TNF alpha), and Transforming Growth Factor beta (TGF beta) have been shown to induce diverse modulations of collagen metabolism and cell proliferation. In the present study, these cytokines were tested for their abilities to regulate collagen formation and proliferation by cultured rat FSCs. FSCs primary culture was established and incubated in the absence or presence of various concentrations of IL-1 alpha, TNF alpha, and TGF beta 1. Tritiated proline and thymidine were used to examine collagen formation and cell proliferation. IL-1 alpha (2.5-10 U/ml) had a concentration-dependent stimulatory effect on FSC proliferation with a maximal response of 160% compared to that of untreated FSCs. This mitogenic effect resulted in slight but significant increases (15-20%) in the net collagen formation. However, when this parameter was standardized relative to DNA content, significant inhibition of both collagen and noncollagen protein formation by IL-1 alpha was demonstrated. TNF alpha also exhibited a similar mitogenic effect but induced a more selective inhibition of collagen formation. In contrast, TGF beta 1 (0.01-1 ng/ml) specifically enhanced collagen formation by 60-80%, as also evidenced by significant increases in the ratio of [3H]hydroxyproline to [3H]proline incorporated in newly formed proteins.(ABSTRACT TRUNCATED AT 250 WORDS)


Chromosomal and temperature-dependent sex determination: the search for a conserved mechanism.
To test the hypothesis that the same (or similar) genes may be involved in chromosomal sex determination and temperature dependent sex determination we investigated the expression of the mammalian testis determining gene SRY in the American alligator (Alligator mississippiensis), a species with temperature dependent sex. We have cloned Alligator SRY-related genes (A-Srys) which constitute three major gene classes with high degrees of sequence homology (45-87%) to mammalian SRY and related genes. Expression analysis and cellular localisation studies using staged embryonic material from male and female incubation temperatures are underway to assess the role of A-Sry genes in temperature dependent sex determination.


Two-dimensional echocardiographic recognition of an aortic intimal flap prolapsing into the left ventricular outflow tract.
A 59 year old man presented with dyspnea and a new murmur of aortic regurgitation. Two-dimensional echocardiography demonstrated a to and fro motion of the intimal flap as it prolapsed into the left ventricle and was thrust into the aorta during diastole and systole, respectively. At surgery, the echocardiographic and angiographic findings were confirmed and a proximal aortic dissection was identified. Prolapse of an intimal flap from the aorta into the left ventricular outflow tract represents a new two-dimensional echocardiographic sign of aortic dissection.


Stable and highly persistent quinoxaline-centered metalloorganic radical anions: preparation, structural, spectroscopic, and computational investigations.
Coordination of diazines such as quinoxaline to transition metals stabilizes radical anions generated by chemical or electrochemical cathodic reduction. However, even though various sorts of radical anionic diazines have been subjected to spectroscopic investigations in the recent past, reports combining structural, solid-state electron paramagnetic resonance (EPR) and computational investigations of kinetically stable species are still missing. In this study, four radical anions derived from tricarbonylmanganese- and tricarbonylrhenium-bound quinoxaline chelates, embedded within a triple-decker architecture, have been prepared from neutral substrates by chemical reduction over alkaline metals (K, Rb); the electronic structure of the latter metalloorganic paramagnetic salts was investigated by the means of structural X-ray diffraction analysis, electrochemistry, solution and crystal EPR spectroscopy, and density functional theory (DFT). Unprecedented structures of three manganese-bound and one rhenium-bound quinoxaline-derived paramagnetic salts were obtained from solutions of the corresponding radical anions crystallized in the presence of cryptand 222. It is inferred from a comparative study of the structures of anionic and neutral quinoxaline complexes that reduction does not have any significant impact over the coordination mode of the metal centers and over the overall geometry of the triple-decker architecture. The most notable changes in the radical-anionic metalloorganic species, as compared to the neutral parent molecules, comprise a slight hapticity shift of the metal-bound benzyl moiety and a weak intraannular distortion of the quinoxalyl core. Single-crystal EPR experiments carried out with the rhenium and manganese compounds produced the respective anisotropic g tensor, which was found in each case to be essentially located at the quinoxalyl fragment. Computations, carried out using DFT methods (B3LYP-LANL2DZ and Becke-Perdew-TZP), corroborated the features suggested by structural analysis. Single-point calculation using the B3LYP functional and various basis sets [LANL2DZ, 6-31G(d), 6-311+G(d), and 6-311+G(2d,p)] provided us with values of anisotropic g tensors and hyperfine coupling constants consistent with those determined experimentally. It is inferred from this study that the two metal centers bound to the nitrogen atoms of the quinoxalyl core contribute in the lowering of the HOMO-LUMO gap in the neutral species. The triple-decker arrangement, which combines chelation of the metal, steric protection, and encapsulation of the central quinoxalyl core, is a stabilizing factor that provides a long-lived character to the radical-anionic species.


The skull in chronic sarcoidosis.
A report of a 63 year old woman with giant osteolytic skull lesions simulating metastatic disease, and generalized cutaneous lesions is presented. Biopsy of a skin lesion revealed non-caseating granulomas compatible with sarcoidosis. The literature dealing with calvarial sarcoidosis is reviewed.