Self-efficacy and attributions for intellectual performance in young and elderly adults.
This study examined subjective assessments of intellectual performance in young (M age = 19.46) and elderly (M age = 75.13) adults. Male and female college students (n = 37) and senior citizens (n = 48) were asked to predict their performance before and after taking fluid and crystallized intelligence tests on two trials. Participants also made causal attributions for their test performance. Elderly participants scored significantly higher on the crystallized test, and young participants scored higher on the fluid test. Men's and women's actual performance did not differ, but the elderly women made lower performance predictions on the fluid test than the elderly men. Both the young and the elderly groups were more accurate in predicting their test performance for the test on which their performance was higher. Accuracy of performance predictions improved across the two trials. Both age groups were more likely to attribute successful performance to ability and unsuccessful performance to task difficulty.


[Competition and the legal ramifications of physician advertising].
Various healthcare reforms have spurred the idea of competition among physicians. As physicians compete for a limited pool of patients advertising has become commonplace. No longer considered an unethical practice, the legal aspects of physician advertising have transformed over the years. The present article describes current laws and statutes regulating physician advertising in Germany. Especially any advertisement likely to mislead or deceive because of a failure to disclose material facts is prohibited. Important cases of German jurisdiction concerning physician advertising are given.


Haplotype mapping uncovers unexplored variation in wild and domesticated soybean at the major protein locus cqProt-003.
The major soy protein QTL, cqProt-003, was analysed for haplotype diversity and global distribution, and results indicate 304 bp deletion and variable tandem repeats in protein coding regions are likely causal candidates. Here, we present association and linkage analysis of 985 wild, landrace and cultivar soybean accessions in a pan genomic dataset to characterize the major high-protein/low-oil associated locus cqProt-003 located on chromosome 20. A significant trait-associated region within a 173 kb linkage block was identified, and variants in the region were characterized, identifying 34 high confidence SNPs, 4 insertions, 1 deletion and a larger 304 bp structural variant in the high-protein haplotype. Trinucleotide tandem repeats of variable length present in the second exon of gene Glyma.20G085100 are strongly correlated with the high-protein phenotype and likely represent causal variation. Structural variation has previously been found in the same gene, for which we report the global distribution of the 304 bp deletion and have identified additional nested variation present in high-protein individuals. Mapping variation at the cqProt-003 locus across demographic groups suggests that the high-protein haplotype is common in wild accessions (94.7%), rare in landraces (10.6%) and near absent in cultivated breeding pools (4.1%), suggesting its decrease in frequency primarily correlates with domestication and continued during subsequent improvement. However, the variation that has persisted in under-utilized wild and landrace populations holds high breeding potential for breeders willing to forego seed oil to maximize protein content. The results of this study include the identification of distinct haplotype structures within the high-protein population, and a broad characterization of the genomic context and linkage patterns of cqProt-003 across global populations, supporting future functional characterization and modification.


Polypeptide composition and histopathologic changes in endomyocardial biopsies from transplanted human hearts.
Sequential postoperative samples of 43 human right ventricular endomyocardial biopsies from four heart transplant patients were evaluated histopathologically to assess microscopic parameters of rejection. Selected pieces of these myocardial biopsies were weighed and homogenized in low ionic strength buffer containing Triton X-100 to extract and to quantitate cardiac actin. Aliquots of the soluble fractions were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Residual pellets were solubilized and also underwent SDS-PAGE. Electrophoretograms were analyzed densitometrically. Actin from biopsies from transplanted human hearts accounted for approximately 40% of Triton X-100 soluble polypeptides. Actin and myosin heavy chain content in the pellet fractions was unchanged as a function of allograft duration. A polypeptide band resolved between 14,000 and 21,000 daltons in the Triton-soluble fraction of four fresh samples correlated with histopathologic changes of moderate acute allograft rejection. A similar band was noted in 11 frozen endomyocardial biopsy specimens without changes of acute rejection. Small actin differences may be found in the transplanted heart, but they do not correlate with rejection. The presence on SDS-PAGE of the polypeptide band found between 14,000 and 21,000 daltons may correlate with proteolysis of cytoplasmic proteins either from rejection or possibly from autolysis after freezing.


Pharmacokinetic Study of NADPH Oxidase Inhibitor Ewha-18278, a Pyrazole Derivative.
In a previous study, the specific NOX1/2/4 inhibitor Ewha-18278 was confirmed as a possible treatment for osteoporosis both in vitro and in vivo. Here, we investigated the pharmacokinetics (PK) of the compound by intravenous (IV) and oral administrations to rats. Dimethyl sulfoxide (DMSO)-based and diazepam injection-based formulations were used to dissolve the compound. In the latter formulation applicable to humans, the changes in PK parameters were monitored at two different concentrations (1 mg/mL and 2 mg/mL). The area under the plasma concentration-time curve from zero time to infinity (AUCinf) of Ewha-18278 was highest in the DMSO-based formulation (2 mg/mL). Also, the concentration was increased 1.6-fold at the low concentration of the diazepam injection-based formulation compared to the high concentration. There was no statistical significance in the AUCinf of the compound between DMSO-based formulation (2 mg/mL) and diazepam injection-based formulation (1 mg/mL). These results suggest that Ewha-18278 can be delivered to humans by both IV and oral routes. In addition, the diazepam injection-based formulation of Ewha-18278 appears to be a suitable candidate for dosage development for future toxicity test and clinical trial.


Reduction in hypoglycemic events in critically ill patients on continuous insulin following implementation of a treatment guideline.
Hyperglycemia is common in critically ill children and appears to be associated with poor outcomes. However, the incidence of hypoglycemia while attempting glycemic control using an insulin infusion may be as high as 25% and hypoglycemia may be an independent risk factor for mortality in critically ill children. An improvement team developed a guideline for initiation and maintenance of insulin infusions for hyperglycemia in critically ill, nondiabetic patients in the pediatric intensive care unit. The guideline included an insulin infusion algorithm that provided an initiating dose, titration instructions, and discontinuation parameters. Guideline recommendations addressed the frequency of bedside blood glucose monitoring and management of symptomatic hypoglycemia while on insulin infusion. The guideline was implemented in late January 2007 and revised in September 2007. Hypoglycemic events in at-risk patients decreased significantly following implementation of the guideline, from 36% to 3%, despite an increase in the total number of patient days on insulin infusion. The average days between hypoglycemic events increased from 21 to 186. Implementation of a guideline to manage critical illness hyperglycemia in nondiabetic, critically ill pediatric patients resulted in a reduction in hypoglycemic events and a sustained increase in the days between such events.


Stent-in-Stent Technique for the Treatment of Proximal Bronchial Restenosis after Insertion of Metallic Stents: A Report of Two Cases.
Endoscopic treatment of a bronchial restenosis previously treated by insertion of a partially covered self-expandable metallic stent (SEMS) can be difficult. Classically, after recanalization of the bronchus, the stent is removed and replaced by a more adapted one. We report on two cases of proximal bronchial restenosis treated by insertion of an additional stent inside the lumen of the previously inserted stent using the stent-in-stent (SIS) technique. The indications for the initial stent were malignancy in Patient 1 and posttransplant bronchial stenosis in Patient 2. Restenosis occurred at the proximal end of the stent within months in both cases. Stent removal and insertion of a new stent were considered, but this option was discarded because of an excessive risk of bronchial perforation and preference towards an alternative approach. In both cases, a second customized SEMS was placed using the SIS technique after ablation of the proximal end stenosis of the stent by argon plasma coagulation and/or dilation with a balloon. Recanalization of the bronchus was achieved in both cases without complications. The SIS technique is a valuable alternative to removal of SEMS in case of proximal bronchial restenosis.


[The potential of photodynamic therapy for the treatment of recurrent respiratory papillomatosis].
The problem of recurrent respiratory papillomatosis (RRP) thus far remains unresolved despite a large number of surgical and conservative methods proposed to address it. Photodynamic therapy is an up-to-date tool for the treatment of various neoplasms based on the interaction between the light and a photosensitizing agent (PA) that gives rise to active oxygen species and causes the death of cells. The potential of photodynamic therapy for the treatment of recurrent respiratory papillomatosis remains to be elucidated. A total of 8 seances of photodynamic therapy were undertaken at the Department of Otorhinolaryngology, I.P. Pavlov Sankt-Peterburg State Medical University, during the period between 2006 and 2010 for the treatment of patients with laryngeal and tracheal lesion, two of them under local anesthesia and the remaining ones under general narcosis. Complete and partial regression of the disease was achieved in 2 and 5 cases respectively. One patient failed to benefit from the treatment. Photodynamic therapy was well tolerated by the patients and produced good functional results; none of them developed adverse effects, there were no signs of refractoriness to the treatment.


Obstructive jaundice: an unusual initial manifestation of intra-abdominal non-Hodgkin lymphoma in a child.
Obstructive jaundice is an unusual manifestation of non-Hodgkin lymphomas in children. Although surgical drainage is one of the initial treatment choices in some cases, usually lymphomatous masses rapidly response to chemotherapy and jaundice decreases due to regression of the mass, without any surgical procedure. The authors report the case of a 16-year-old girl who presented with biliary obstruction due to a neoplasm involving the duodenum. Histological examination of the specimen, which was taken from the mass by endoscopic biopsy, revealed Burkitt lymphoma infiltrating the duodenum. Chemotherapy including cyclophosphamide was started immediately. In a few days, jaundice decreased rapidly by the shrinkage of the mass. Neither surgery nor percutaneous drainage were needed. In conclusion, biliary tract obstruction due to non-Hodgkin lymphoma can be effectively treated with chemotherapy alone without any surgical procedure.


Strongyloidiasis Current Status with Emphasis in Diagnosis and Drug Research.
Strongyloidiasis is a parasitic neglected disease caused by the nematode Strongyloides stercoralis affecting 30 to 100 million people worldwide. Complications, strongly associated with alcoholism, organ transplants, and HTLV-1 virus, often arise due to late diagnosis, frequently leading to patient death. Lack of preemptive diagnosis is not the only difficulty when dealing with this parasite, since there are no gold standard diagnostic techniques, and the ones used have problems associated with sensitivity, resulting in false negatives. Treatment is also an issue as ivermectin and benzimidazoles administration leads to inconsistent cure rates and several side effects. Researching new anti-Strongyloides drugs is a difficult task since S. stercoralis does not develop until the adult stages in Mus musculus (with the exception of SCID mice), the main experimental host model. Fortunately, alternative parasite models can be used, namely, Strongyloides ratti and S. venezuelensis. However, even with these models, there are other complications in finding new drugs, which are associated with specific in vitro assay protocol steps, such as larvae decontamination. In this review, we highlight the challenges associated with new drug search, the compounds tested, and a list of published in vitro assay methodologies. We also point out advances being made in strongyloidiasis diagnosis so far.


[Is the marriage market unbalanced? The case of Mexico in 1980].
"The objective of this article is to present the results obtained when estimating how balanced, in numerical terms, the Mexican population of marriageable age [12 to 50 years old] was in 1980, in relation to its structure by age and sex, as well as the timing of its nuptiality. This estimate was made for both the state and national levels, using as a source of information the 1980 Census...." (SUMMARY IN ENG)


[Changes in marriage patterns in Java].
"The paper reviews the changes that have taken place in the marriage pattern among rural Javanese. Low age at marriage and decision regarding marriage made by the parents were the norms in the past. Consummation of marriage was frequently delayed. Although marriage has been highly valued in the society, [the] divorce rate was high. With the advance of education and social progress in general, changes have taken place. Age at marriage has gone up, parental role in marital decision making has declined and the divorce rate has dropped significantly." (SUMMARY IN ENG)


Novel fibrinogen truncation with deletion of Bbeta chain residues 440-461 causes hypofibrinogenaemia.
A 24-year-old male with hepatitis C was initially diagnosed with hypofibrinogenaemia during investigations prior to a liver biopsy. He had a low functional and gravimetric fibrinogen concentration of 1.0 mg/mL and DNA sequencing of all exons, exon-intron boundaries and promoter regions of the fibrinogen Aalpha, Bbeta, and gamma genes revealed a single heterozygous g-->a mutation at nucleotide 8035 of the Bbeta gene. This creates a premature stop at the Trp 440 codon and results in a 22-residue truncation of the Bbeta chain. Analysis of purified plasma fibrinogen by SDS PAGE, reverse phase HPLC and ESI MS, however, failed to detect any of the truncated chains in the plasma fibrinogen. The non-expression of aberrant molecules was further confirmed by functional analysis, which revealed normal fibrin polymerisation. The principal structural feature of the independently folding betaD domain is its five-stranded anti-parallel beta sheet. The deletion here of residues 440 to 461 removes the second strand from this sheet structure and appears to impact on the viability of the nascent chain and its ability to be incorporated into mature fibrinogen molecules. The mutation does not however provoke the formation of hepatic inclusion bodies.


Syntheses and chemistry of hypervalent cyclo-R4Sb4, cyclo-(RSbE)n[R = 2-(Me2NCH2)C6H4, E = O, S] and precursors.
The cyclostibane R(4)Sb(4)(1)(R = 2-(Me(2)NCH(2))C(6)H(4)) was synthesized by reduction of RSbCl(2) with Mg in THF or with Na in liquid NH(3). The reaction of 1 with [W(CO)(5)(THF)] gives the stibinidene complex RSb[W(CO)(5)](2)(2). RSbCl(2) and (RSbCl)(2)E [E = O (6), E = S (8)] react with KOH or Na(2)S in toluene/water to give the heterocycles (RSbE)(n)[E = O, n= 3 (3); E = S, n= 2 (4)]. The chalcogeno-bridged compounds of the type (RSbCl)(2)E [E = O (6), E = S (8)] were synthesized by reaction of RSbCl(2) with KOH or Na(2)S in toluene/water, but also by reaction of RSbCl(2) with the heterocycles (RSbE)(n). The compounds (RSbI)(2)O (7) and (RSbBr)(2)S (9) were prepared via halogen-exchange reactions between (RSbCl)(2)E and NaI (E = O) or KBr (E = S) or by reactions between RSbI(2) and KOH or RSbBr(2) and Na(2)S. The reaction of cyclo-(RSbS)(2) with W(CO)(5)(THF) in THF results in trapping of the cis isomer in cyclo-(RSbS)(2)[W(CO)(5)](5). The solution behaviour of the compounds was investigated by (1)H and (13)C NMR spectroscopy. The molecular structures of compounds 1-7 and 9 were determined by single-crystal X-ray diffraction.


Compliance with the smoke-free public places legislation in Nepal: A cross-sectional study from Biratnagar Metropolitan City.
Smoke-free legislation banning tobacco smoking in public places was implemented across Nepal in 2014 with the ambition to reduce the impact of second-hand smoking. As part of a comprehensive policy package on tobacco control, the implementation of the legislation has seen a marked reduction in tobacco consumption. Yet there remains uncertainty about the level of compliance with smoke-free public places. This study assesses the compliance with smoke-free laws in public places and the factors associated with active smoking in public places in Biratnagar Metropolitan City, Nepal. A cross-sectional study was conducted in the Biratnagar metropolitan city in Province 1 of Nepal from July to December 2019. A total of 725 public places within the metropolitan city were surveyed using a structured survey tool. Active smoking was the primary outcome of the study which was defined as smoking by any person during the data collection time at the designated public place. The overall compliance with smoke-free legislation was 56.4%. The highest compliance (75.0%) was observed in Government office buildings. The lowest compliance was observed in eateries, entertainment, and shopping venues (26.3%). There was a statistically significant association between active smoking and the presence of 'no smoking' notices appended at the entrance and the odds of active smoking in eateries, entertainment, hospitality, shopping venues, transportations and transits was higher compared to education and health care institutions. None of the 'no smoking' notices displayed fully adhered to the contents as prescribed by the law. As more than half of the public places complied with the requirements of the legislation, there was satisfactory overall compliance with the smoke-free public places law in this study. The public venues (eateries, shopping venues and transportations) that are more frequently visited and have a high turnover of the public have lower compliance with the legislation. The content of the message in the 'no smoking' notices needs close attention to adhere to the legal requirements.


Quantification and visualization of carotid segmentation accuracy and precision using a 2D standardized carotid map.
This paper describes a framework for vascular image segmentation evaluation. Since the size of vessel wall and plaque burden is defined by the lumen and wall boundaries in vascular segmentation, these two boundaries should be considered as a pair in statistical evaluation of a segmentation algorithm. This work proposed statistical metrics to evaluate the difference of local vessel wall thickness (VWT) produced by manual and algorithm-based semi-automatic segmentation methods (ΔT) with the local segmentation standard deviation of the wall and lumen boundaries considered. ΔT was further approximately decomposed into the local wall and lumen boundary differences (ΔW and ΔL respectively) in order to provide information regarding which of the wall and lumen segmentation errors contribute more to the VWT difference. In this study, the lumen and wall boundaries in 3D carotid ultrasound images acquired for 21 subjects were each segmented five times manually and by a level-set segmentation algorithm. The (absolute) difference measures (i.e., ΔT, ΔW, ΔL and their absolute values) and the pooled local standard deviation of manually and algorithmically segmented wall and lumen boundaries were computed for each subject and represented in a 2D standardized map. The local accuracy and variability of the segmentation algorithm at each point can be quantified by the average of these metrics for the whole group of subjects and visualized on the 2D standardized map. Based on the results shown on the 2D standardized map, a variety of strategies, such as adding anchor points and adjusting weights of different forces in the algorithm, can be introduced to improve the accuracy and variability of the algorithm.


Proteomic analysis of undiluted lung epithelial lining fluid.
Proteomics is increasingly leading to biomarker discovery in human disease. Epithelial lining fluid (ELF), until now only recovered indirectly, diluted in BAL fluid, is an attractive sample for lung disease proteomics. The direct recovery of undiluted ELF is now possible using a bronchoscopic microsampling (BMS) probe. In this preliminary study of anesthetized ventilated rabbits, we applied this probe to recover ELF and to analyze the resulting samples with the aim of determining their potential in lung disease biomarker discovery. In order to do so, a method was devised and evaluated in preliminary experiments both for nonbronchoscopic use of the probe and for recovering undiluted ELF from probe tips. To verify the proteomic potential of the sample, the recovered ELF was separated by one-dimensional polyacrylamide gel electrophoresis, and the resulting lane was cut into multiple fractions, each of which was digested and analyzed by liquid chromatography tandem mass spectrometry. The identified proteins were then searched against Medline for association with broad categories of lung disease. Nonbronchoscopic use of the probe allowed successful ELF sampling and the recovery of undiluted ELF from probe tips. Proteomic analysis showed that ELF contains many proteins that have already been reported as being associated with lung disease as well as proteins potentially correlated with lung disease. This preliminary study of undiluted ELF, as recovered by the BMS probe, shows that it may be an ideal sample for lung proteomics. The potential application of this sampling technique in various lung diseases will need to be confirmed by future studies.


Effects of vitamin D3 metabolites on cytosolic free calcium in confluent mouse osteoblasts.
A fluorescent Ca2+ indicator, acetoxymethyl Quin2, was used to quantify changes in the cytosolic free calcium concentration ([Ca2+]i) of confluent mouse osteoblasts. 1,25 - Dihydroxycholecalciferol (1,25 - (OH)2D3, 10-100 pM), 25-hydroxycholecalciferol (25-(OH)D3, 10-100 nM), parathyroid hormone (PTH(1-84), 0.1-10 nM), and prostaglandin E2 (PGE2, 10-1000 nM) all induced immediate (t less than 15 s) transient increases in [Ca2+]i, from a basal level of 135 +/- 8 nM to levels of 179-224 nM. These increases rapidly returned to a plateau approximately 10% higher than the basal level. 24,25-Dihydroxycholecalciferol (24,25-(OH)2D2, 0.1-10 nM) induced a rapid increase in [Ca2+]i which remained elevated for 5 min before decreasing. The 1,25-(OH)2D3- and PTH-induced spikes were abolished by the prior addition of EGTA and Ca2+ entry blockers (verapamil, nifedipine, 1 microM) while the responses to 25-(OH)D3, 24,25-(OH)2D3, and PGE2 were unaffected. Addition of 1,25-(OH)2D3 + EGTA or PTH + EGTA caused enhanced Ca efflux. Addition of drugs which interfere with calcium sequestration by the endoplasmic reticulum (ER) (caffeine, 4 mM; 8-(diethyl-amino)-octyl 3,4,5-trimethoxybenzoate HCl, 0.5 mM) or mitochondria (antimycin, 10 microM; oligomycin, 5 microM) showed that 25-(OH)D3 and PGE2 mainly mobilized Ca2+ from ER. 1,25-(OH)2D3 and bovine PTH caused a transient increase in [Ca2+]i, 70% of which resulted from Ca2+ influx from outside the cells and 30% by release from the ER. The [Ca2+]i increase induced by 24,25-(OH)2D3 included a 30% contribution from the ER and 70% from the mitochondria.


Synthesis and characterization of hyperbranched poly(glycidol) modified with pH- and temperature-sensitive groups.
Hyperbranched poly(glycidol)s with varying degrees of polymerization were modified by reaction with succinic anhydride and isopropylamine to obtain novel pH- and thermosensitive polymers. These polymers exhibited phase transitions in response to decreasing pH and/or increasing temperature, depending on the degree of polymerization and the ratio of succinyl group to N-isopropylamide. It was possible to harvest a bioactive molecule, rose bengal, from solution using the phase transition of thermosensitive hyperbranched poly(glycidol).


[Hypertrophic obstructive cardiomyopathy: surgical treatment].
Hypertrophic obstructive cardiomyopathy (HOCM) is an autosomal, dominant inherited disease of the myocardium which leads slowly to increasing subvalvular, septal and left ventricular hypertrophy and deterioration of systolic and diastolic left ventricular compliance. Difficult molecular-genetic investigations localized genetic defects on different chromosomes. The disease is pathological-anatomically characterized by asymmetric subvalvular (aortic) septal hypertrophy and left ventricular outflow tract obstruction resulting in additional left ventricular hypertrophy and dysfunction. Histologically the myocytes are hypertrophied, exhibit atypical branching (disarray), and there is a high amount of interstitial connective tissue. In our biopsy material (from myectomies) dysplasia could be detected in more than 30% of dysplastic intramural arteries with partly extential media. These changes may indicate microcirculatory disturbances resulting in arrhythmias, syncopes, sudden death, and anginal pain on the basis of microcirculatory disturbances and scar development. Today the discussion of DDD-pacemaker therapy has resumed, but one must wait for definite results, especially in patients in whom surgical treatment seems to be the best choice. The indication for surgical treatment, which usually is transaortic subvalvular myectomy (Morrow) and modifications, is very restrictive. Only patients in clinical degree III (NYHA) after long-term medical treatment are candidates for surgery. In some mainly younger patients the indication in lower clinical degrees was accepted because of a family history with sudden death and personal experience of syncope, life-threatening tachycardia, or after resuscitation. In the period 1963 to 1994 466 patients were operated upon. The mean age was 44.9 years (range 3 months to 82 years). Total early mortality was 4.9% (n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)


Group B streptococcal type II and III conjugate vaccines: physicochemical properties that influence immunogenicity.
Recent efforts toward developing vaccines against group B streptococci (GBS) have focused on increasing the immunogenicity of GBS polysaccharides by conjugation to carrier proteins. However, partial depolymerization of GBS polysaccharides for the production of vaccines is a difficult task because of their acid-labile, antigenically critical sialic acids. Here we report a method for the partial depolymerization of type II and III polysaccharides by mild deaminative cleavage to antigenic fragments with reducing-terminal 2,5-anhydro-d-mannose residues. Through the free aldehydes of their newly formed end groups, the fragments were conjugated to tetanus toxoid by reductive amination. The resulting conjugates stimulated the production in animals of high-titer type II- and III-specific antibodies which induced opsonophagocytic killing of type II and III strains of group B streptococci. For the type II conjugates, immunogenicity increased as oligosaccharide size decreased, whereas for type III conjugates, the size of the oligosaccharides did not significantly influence immunogenicity. When oligosaccharides of defined size were conjugated through sialic acid residues, the resulting cross-linkages were shown to affect immunogenicity. When oligosaccharides were conjugated through terminal aldehyde groups generated by deamination, modification of the exocyclic chain of sialic acid did not influence immunogenicity.


Programmed Intermittent Epidural Bolus versus Continuous Epidural Infusion in Major Upper Abdominal Surgery: A Retrospective Comparative Study.
Although recent evidence shows that the programmed intermittent epidural bolus can provide improved analgesia compared to continuous epidural infusion during labor, its usefulness in major upper abdominal surgery remains unclear. We evaluated the effect of programmed intermittent epidural bolus versus continuous epidural infusion on the consumption of postoperative rescue opioids, pain intensity, and consumption of local anesthetic by retrospective analysis of data of patients who underwent major upper abdominal surgery under ultrasound-assisted thoracic epidural analgesia between July 2018 and October 2020. The primary outcome was total opioid consumption up to 72 h after surgery. The data of postoperative pain scores, epidural local anesthetic consumption, and adverse events from 193 patients were analyzed (continuous epidural infusion: n = 124, programmed intermittent epidural bolus: n = 69). There was no significant difference in the rescue opioid consumption in the 72 h postoperative period between the groups (33.3 mg [20.0-43.3] vs. 28.3 mg [18.3-43.3], p = 0.375). There were also no significant differences in the pain scores, epidural local anesthetic consumption, and incidence of adverse events. Our findings suggest that the quality of postoperative analgesia and safety following major upper abdominal surgery were comparable between the groups. However, the use of programmed intermittent epidural bolus requires further evaluation.


Mechanism of the hysteresis effect in rate-dependent photomultiplier gain variations.
The hysteresis effect in rate-dependent photomultiplier gain variations observed in a particular ten-stage tube was extensively studied to clarify the mechanism involved. The transition points or count rates at which abrupt gain changes take place are measured with respect to the anode and ninth dynode pulses as a function of light pulse intensity and applied high voltage. The experimental results show that the transition occurs at constant average currents and is attributed to certain physical processes on the ninth dynode. Besides, extensive measurements of the hysteresis curves are performed with respect to the ninth dynode pulse for various biases applied to the tenth dynode. The results clearly indicate that the transitions are due to sudden changes in surface potential on the ninth dynode, presumably resulting from dielectric breakdown in the dynode surface layer. In accordance with these and other measurements, a possible physical mechanism is proposed to interpret the hysteresis effect. With the proposed mechanism, temperature effect on the transition points and possible dependence of the hysteresis effect on dynode structure are briefly discussed.


Highly nonplanar, electron deficient, N-substituted tetra-oxocyclohexadienylidene porphyrinogens: structural, computational, and electrochemical investigations.
The structures and electrochemistry of N-benzylated meso-tetrakis (3,5-di-tert-butyl-4-oxo-cyclohexa-2,5-dienylidene) porphyrinogens have been investigated. Structural determinations reveal the isomeric identity of the products obtained from the N-alkylation of the parent meso-tetra (oxo-cyclohexadienylidene) porphyrinogen. The compounds are subject to increased macrocyclic deformations upon increasing N-substitution culminating in the tetra-N-benzyl derivative, which has a buckling superimposed on the already highly puckered macrocycle. The electrochemical analyses emphasize the electron deficiency of the N-benzylated meso-tetra(oxo-cyclohexadienylidene) porphyrinogens and indicate that they can be considered as quinones conjugated via the unsaturated tetrapyrrolic macrocycle. The N-benzylated compounds studied form stable and well-defined pi-cation radical and pi-anion radical species because of their highly conjugated nature. Ab initio molecular orbital calculations at the B3LYP/3-21G() level confirmed the high degree of conjugation between tetrapyrrole and meso substituents and also gave good agreement between calculated and experimentally determined HOMO-LUMO band gap energies.


[Thought on several problems of clinical revaluation of post-marketing herb research].
The revaluation of post-marketing herb is a complex research work, which concerns widely content and difficult to put it into practice. The starting of our country's revaluation post-marketing herb was comparatively late. It should profect it both in laws and regulations mechanism as well as technological specification. This article is try to focus on some attention problems in revaluation of postmarketing herb process. Such as the laws and regulations demand, the basement and the subject of revaluation of post-marketing herb.


Responses to COVID-19: The role of governance, healthcare infrastructure, and learning from past pandemics.
The ongoing COVID-19 outbreak has revealed vulnerabilities in global healthcare responses. Research in epidemiology has focused on understanding the effects of countries' responses on COVID-19 spread. While a growing body of research has focused on understanding the role of macro-level factors on responses to COVID-19, we have a limited understanding of what drives countries' responses to COVID-19. We lean on organizational learning theory and the extant literature on rare events to propose that governance structure, investment in healthcare infrastructure, and learning from past pandemics influence a country's response regarding reactive and proactive strategies. With data collected from various sources and using an empirical methodology, we find that centralized governance positively affects reactive strategies, while healthcare infrastructure and learning from past pandemics positively influence proactive and reactive strategies. This research contributes to the literature on learning, pandemics, and rare events.


Assessing the end-of-life impacts of buildings.
This paper builds on previous research on end of life of products by synthesizing some of the theories proposed in the literature and presenting a method for environmental decision-making related to buildings. This is achieved through different solutions, but most significantly through the use of hybrid life-cycle assessment and the definition of allocation boundaries in a way that decreases the uncertainty associated with technologicalforecasting. Results show that there is no significant difference between the results of two major end-of-life assessment approaches (attributional and consequential), and that the choice between the use of one or the other for buildings may not be a critical decision. Assessing the impacts of recycling polices requires accounting for product substitutions, market analysis, and the full supply chain impacts of the recycling chains. Increasing the recycling of concrete from deconstructed buildings from the current 27% rate to 50% could yield a 2-3% (2.7-5.6 million metric tons of CO2 equivalents) reduction in buildings' greenhouse gas emissions, or the equivalent of removing 408,000-847,000 typical cars from U.S. roads.


Suppression of matrix metalloproteinase production from nasal fibroblasts by fluticasone propionate in vitro.
To examine the influence of fluticasone propionate (FP) on matrix metalloproteinase (MMP) production from nasal polyp fibroblasts in vitro. Fibroblasts derived from five nasal polyps were stimulated with tumor necrosis factor (TNF)-alpha in the presence of various concentrations of FP. The influence of FP on MMP production was assessed by examining the levels of MMP-2 and -9 in culture supernatants using ELISA. We also examined the influence of FP on MMP mRNA expression using reverse transcriptase polymerase chain reaction. The addition of FP caused significant suppression of MMP-2 and -9 production from nasal polyp fibroblasts in response to TNF-alpha stimulation. MMP mRNA expression was also suppressed by the addition of FP to cell cultures. The minimum concentration of the agent required to cause suppression was 10(-5) M. These results suggest that the inhibitory action of FP on tissue remodeling may underlie the clinical efficacy of corticosteroids in nasal polyposis.


Tenascin C in radiation-induced lung damage: Pathological expression and serum level elevation.
Radiation-induced lung damage (RILD) is a critical problem in lung cancer radiotherapy, and it is difficult to predict its severity. Although no biomarkers for RILD have been established, tenascin C (TNC) is an extracellular matrix glycoprotein involved in the remodeling of damaged tissues and has been implicated in inflammation and fibrosis. We report the unique case of a 36-year-old man with adenocarcinoma of the lung, Union for International Cancer Control stage IIIB, who was treated with radiotherapy before lung surgery. The surgical specimen showed histopathological expression of TNC in the region where radiation pneumonitis was observed radiographically. Serum TNC levels were elevated after radiotherapy. In this case, TNC is suggested to be implicated in RILD and may be a potential candidate as a biomarker for the onset and severity of the condition.


Study of a calculation method for healthy life expectancy.
"To develop a calculation method for healthy life expectancy which would be suitable for China we analyzed the healthy life expectancy of urban residents in China, employing data on residents' deaths and data available from the 1993 national survey for health services and family health conditions.... Results of the study show that the ratio of healthy life expectancy to life expectancy decreases with the increase of the residents' age; healthy life expectancy for females is higher than that for males; [and] healthy life expectancy for residents of large cities is lower than that for residents of medium and small cities."


Use of diagnostic imaging in Australian general practice.
The BEACH program, a continuous national study of general practice activity in Australia, gives us an overview of diagnostic imaging ordered by Australian general practitioners. This provides a backdrop against which the theme articles in this issue of Australian Family Physician can be further considered.


Sonographic Characterization of Arterial Dissections in Takayasu Arteritis.
Takayasu arteritis is a relatively rare chronic nonspecific form of large-vessel vasculitis in which the involved vessels develop stenoses, occlusions, dilatations or aneurysms, and dissections. Dissections of the arteries in patients with Takayasu arteritis are not well understood. In this study, we explored the sonographic characterization of these rare complications secondary to Takayasu arteritis. We evaluated arterial dissections in 72 patients with a clinical diagnosis of Takayasu arteritis by vascular sonography and transthoracic echocardiography. We analyzed the dissection distribution and morphologic characteristics of the dissected intima/layer and lumen of the involved vessels. Twelve of 72 patients had arterial dissections, in whom 16 dissected segments were identified. The involved arteries included the carotid, subclavian, vertebral, brachial, celiac, and femoral arteries, aortic arch, and abdominal aorta. The dissection lesions occurred at any age and coexisted with the aforementioned injuries. Evaluation of the dissected intima/layer and the involved lumen by sonography was technically complicated. The morphologic characteristics of the dissected intimae and involved lumens were complex, with most of the dissected intimae/layers having the characteristic "macaroni" sign in the arterial wall. High-frequency and high-resolution sonography, color Doppler flow imaging, and other techniques were useful in elucidating greater lesion details. Arterial dissections in Takayasu arteritis can involve any anatomic vessel location and have complex morphologic characteristics. Sonography is the optimal technique for diagnosis and follow-up of patients with Takayasu arteritis and dissections.


Presidential address, 1995. Surgery 2000: a look back to the future.
The present demoralized state of Canadian surgery is due to a number of short-term influences. They include financial restraints, the desire of government agencies to off-load blame for unpopular decisions onto doctors and altered public expectations. The major long-term challenge will be a shortage of physicians and a severe shortage of general surgeons because of the superimposition of longer-term trends in medical demographics on short-term political reactions to a perceived oversupply of doctors. General surgeons need to identify the significant, long-term threats and challenges. If they can do this and plan their responses knowledgably, with some measure of altruism, the future in general surgery will be a bright one for present and future residents and medical students.


Response of broiler chicks to dietary Rhazya stricta and Nigella sativa.
1. Rhazya stricta leaves and Nigella sativa seeds were fed to 7-d-old Hibro broiler chicks at 20 and 100 g/kg of the diet for 7 weeks. Although 20 and 100 g/kg N. sativa seed diets did not adversely affect growth, a decrease in body weight and feed efficiency and hepatonephropathy were observed in the chicks fed on the 100 g/kg R. stricta diet. 2. These changes, associated with macrocytic hypochromic anaemia, were correlated with alterations in serum aspartate transaminase' (AST) and alanine transaminase (ALT) activities and concentrations of total protein, albumin, globulin, cholesterol, calcium and other serum constituents. 3. The effect of 20 g/kg R. stricta diet on chicks was not associated with development of biliary hyperplasia or catarrhal enteritis after 7 weeks of treatment.


Transition from spherical to irregular dispersed phase in water/oil emulsions.
Bulk properties of transparent and dilute water in paraffin oil emulsions stabilized with sodium dodecyl sulfate (SDS) are analyzed by optical scanning tomography. Each scanning shot of the considered emulsions has a precision of 1 μm. The influence of aluminum oxide nanoparticles in the structure of the water droplets is investigated. Depending on concentrations of SDS and nanoparticles, a transition occurs in their shape that changes from spherical to polymorphous. This transition is controlled by the SDS/alumina nanoparticles mixing ratio and is described using an identification procedure of the topology of the gray level contours extracted from each images. The transition occurs for a critical mixing ratio of Rcrit ≈ 0.05 which does not significantly depend on temperature and electrolyte concentration. This structural change seems to be a general feature when emulsifying dispersions and most probably involves both interfacial and bulk phenomena.


Cloning and sequence analysis of thermostable direct hemolysin-related hemolysin gene of Vibrio parahaemolyticus.
To establish a method for cloning thermostable direct hemolysin-related hemolysin (trh) gene of Vibrio parahaemolyticus (Vp). After enrichment by PCR, the trh gene, along with the plasmid DNA of pGEX-3X, was digested with two enzymes followed by linkage of the gene and the plasmid, the product of which was transferred into E.coli DH5alpha. Identification of the recombinant plasmid was performed by means of PCR, digestion and sequence analysis. A fragment about 600 bp was identified in the PCR product of Vp14-91, which was also seen in the product of PCR and enzyme digestion of the recombinant fragment. Sequence analysis demonstrated a homology of 99.1% between the trh gene and the reference gene available in the GenBank. trh gene has been successfully cloned with its sequence analyzed, which prepares the ground for developing gene probe and protective vaccine against Vp.


Alkaline Band Formation in Chara corallina: Due to OH Efflux or H Influx?
The nature of the transport system responsible for the establishment of alkaline bands on cells of Chara corallina was investigated. The transport process was found to be insensitive to external pH, provided the value was above a certain threshold. At this threshold (pH 5.1 to 4.8) the transport process was inactivated. Transport function could be recovered by raising the pH value of the external solution. The fastest rate of recovery was always obtained in the presence of exogenous HCO(3) (-).Experiments in which plasmalemma integrity was modified using 10 millimolar K(+) treatment were also performed. Alkaline band transport was significantly reduced in the presence of 10 millimolar K(+), but the system did not recover, following return to 0.2 millimolar K(+) solutions, until the transport site was reexposed to exogenous HCO(3) (-).The influence of presence and absence of various cations on both alkaline band transport and total H(14)CO(3) (-) assimilation was examined. No specific cation requirement (mono- or divalent) was found for either process, except the previously established role of Ca(2+) at the HCO(3) (-) transport site. The alkaline band transport process exhibited a general requirement for cations. This transport system could be partially or completely stalled in low cation solutions, or glass-distilled water, respectively. The results indicate that no cationic flux occurs across the plasmalemma in direct association with either the alkaline band or HCO(3) (-) transport systems.It is felt that the present results offer support for the hypothesis that an OH(-) efflux transport system (rather than a H(+) influx system) is responsible for alkaline band development in C. corallina. The results support the hypothesis that OH(-) efflux is an electrogenic process. This OH(-) transport system also appears to contain two allosteric effector sites, involving an acidic group and a HCO(3) (-) ion.


SEF/IL-17R (SEFIR) is not enough: an extended SEFIR domain is required for il-17RA-mediated signal transduction.
IL-17, the hallmark cytokine of the Th17 population, mediates immunity to extracellular pathogens and promotes autoimmune immunopathology. The signaling mechanisms triggered by the IL-17 receptor (IL-17RA) and related receptors are strikingly different from other cytokine subclasses. Namely, IL-17Rs contain a conserved SEF/IL-17R (SEFIR) subdomain that engages Act1, leading to activation of TRAF6, NF-κB, and other events. Although the SEFIR is critical for signaling, the molecular details of the functional subdomains within IL-17RA remain poorly characterized. Here, we provide a detailed structure-function analysis delineating the C-terminal boundary of the SEFIR-containing region of IL-17RA. We show that functionality of this domain requires a large extension to the previously identified SEFIR motif. In contrast to the SEFIR, this extension is not conserved among IL-17R family members. Surprisingly, Act1 recruitment is not sufficient for downstream signaling activation, whereas ubiquitination of TRAF6 correlates tightly with functional receptors. We further demonstrate that IL-17RA exhibits signaling properties that are nonredundant with other IL-17R family members. Finally, we report that IL-17 signals synergistically with lymphotoxin-α3, using the same signaling motifs within IL-17RA. These studies provide new insight into the structure-function relationships of IL-17RA and reveal distinct signaling differences among IL-17R family members.


[Formolization of the bladder mucosa for hemostatic purposes].
The authors have used formalin solutions for the control of haematuria induced by bladder tumours. The 10 percent solution was efficient but induced severe side effects, such as peritonitis due to vesical necrosis, urethral fistulae, etc. The 1 percent solution is also efficient, and the local aggressivity is practically lacking, provided only 1--3 applications are carried out. The method should be used only in cases of haematuria that cannot be stopped by classical conservative means and in which surgery is not indicated, either temporarily or definitively.


[Intra-operative echocardiography].
The usefulness of intra-operative echocardiography, especially, transesophageal echocardiography (TEE) was highlighted. Preoperative re-evaluation by TEE provides new information that is not obtainable by other preoperative examinations. In addition, real-time 3-dimensional TEE has recently become available, which may bring a lot of benefits for the mitral valve surgery. Intra-operative TEE examination is useful in detecting the proper positioning of the catheter for cardiopulmonary bypass, the trapped air, residual shunt, and other abnormalities. Early postoperative TEE exam is also useful in preventing the risk of re-operation. Despite some limitations, intra-operative TEE is one of the important technology to support the thoracic and cardiovascular surgery.


Waterborne Pathogens: The Protozoans.
Waterborne diseases associated with polluted recreational and potable waters have been documented for more than a century. Key microbial protozoan parasites, such as Cryptosporidium and Giardia, are causative agents for gastrointestinal disease worldwide. Although not a first-line diagnostic approach for these diseases, medical imaging, such as radiography, computed tomography, magnetic resonance imaging, ultrasonography, and nuclear medicine technologies, can be used to evaluate patients with long-term effects. This article describes protozoan pathogens that affect human health, treatment of common waterborne pathogen-related diseases, and associated medical imaging.


Drug-induced hypersensitivity syndrome following temozolimide for glioblastoma multiforme and the role of desensitization therapy.
Temozolomide is an oral alkylating agent used as first line treatment of glioblastoma multiforme (GBM). It has also been used in the treatment of certain solid tumors such as metastatic melanoma. Commonly reported adverse effects include nausea and vomiting, constipation, headache, fatigue and myelosuppression. Cutaneous hypersensitivity reactions are rare and include an urticarial hypersensitivity reaction, alopecia, and Stevens-Johnson syndrome. To our knowledge, there are minimal reports of temozolomide-induced DRESS syndrome. We present a 54-year-old man with glioblastoma multiforme who presented with a fever, diarrhea and progressively worsening rash 6 weeks after starting temozolomide. The patient was diagnosed recurrent DRESS syndrome and restarted on a gradual prednisone taper with resolution over the following weeks. Unfortunately, the patient was unable to be followed long-term due to relocation to a different state. To our knowledge, there are minimal reports of temozolomide-induced DRESS syndrome. The diagnosis can be life-threatening, which makes management of patients with GBM and no alternative treatment option challenging. The use of de-sensitization therapy to temozolomide has been proposed for the management of severe adverse cutaneous reactions.


Association between childhood trauma and dissociation among patients with borderline personality disorder.
To examine the relationship between childhood trauma and dissociative experience in adulthood in patients with borderline personality disorder. Dissociative experiences scale scores and subscale scores for the Childhood Trauma Questionnaire were correlated in 139 patients. Patients were dichotomized into high or low dissociators using the Median Dissociative Experiences Scale score as the cut-off. Childhood Trauma Questionnaire Subscale scores for emotional and physical abuse and emotional neglect but not sexual abuse correlated significantly with Dissociative Experiences Scale scores. High dissociators reported significantly greater levels of emotional abuse, physical abuse, emotional neglect and physical neglect but not sexual abuse than low dissociators. Patients with borderline personality disorder therefore demonstrated levels of dissociation that increased with levels of childhood trauma, supporting the hypothesis that traumatic childhood experiences engender dissociative symptoms later in life. Emotional abuse and neglect may be at least as important as physical and sexual abuse in the development of dissociative symptoms.


General practice, primary care, and health service psychology: concepts, competencies, and the Combined-Integrated model.
The profession of psychology is being impacted profoundly by broader changes within the national system of health care, as mental and behavioral health services are being recognized as essential components of a comprehensive, preventive, and cost-efficient primary care system. To fully define and embrace this role, the discipline of professional psychology must develop a shared disciplinary identity of health service psychology and a generalized competency-based model for doctoral education and training. This very framework has been adopted by Combined-Integrated (C-I) doctoral programs in professional psychology, which train across the practice areas (clinical, counseling, and school psychology) to provide a general and integrative foundation for their students. Because C-I programs produce general practitioners who are competent to function within a variety of health service settings, this innovative training approach has great potential to educate and train psychologists for a changing health care marketplace.


Gillisia myxillae sp. nov., a novel member of the family Flavobacteriaceae, isolated from the marine sponge Myxilla incrustans.
A yellow-pigmented, Gram-negative, rod-shaped, strictly aerobic bacterium (strain UST050418-085(T)) was isolated from the surface of a marine sponge, Myxilla incrustans, at Friday Harbor, WA, USA. The DNA G+C content of this strain was 34.6 mol%. The predominant fatty acids were i15 : 0, a15 : 0, i15 : 1, i16 : 0, i17 : 0 3-OH, 17 : 0 2-OH and summed feature 3, comprising i15 : 0 2-OH and/or 16 : 1omega7c (altogether representing 69.0 % of the total fatty acids). MK-6 was the only respiratory quinone detected. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the closest relatives of UST050418-085(T) were members of the genus Gillisia, with sequence similarities of 93.2-96.6 %. Strain UST050418-085(T) differed from its closest relatives by 11 to 18 phenotypic traits. Molecular evidence and phenotypic characteristics suggest that strain UST050418-085(T) represents a novel species within the genus Gillisia. The name Gillisia myxillae sp. nov. is proposed, with UST050418-085(T) (=JCM 13564(T)=NRRL B-41416(T)) [corrected] as the type strain.


Mediterranean diet, lifestyle and quality of life in Sardinian patients affected with Hidradenitis suppurativa.
Hidradenitis suppurativa is a chronic inflammatory skin disease with a strong negative impact on physical and psychological health. Obesity, especially visceral adiposity, but also smoking or unhealthy nutritional habits, have been reported to be significantly associated with hidradenitis suppurativa. Case-control study in 35 patients of both sexes affected with hidradenitis suppurativa, and 35 healthy subjects matched for sex, age, and geographic origin (Sardinia, Italy). Several anthropometric measures (body mass index, waist circumference, body composition), lifestyle (Mediterranean diet adherence, and physical activity level), and the perceived physical and mental health status were evaluated in case and controls. Hidradenitis patients showed significantly higher values of body mass index, waist circumference, body composition, fat mass, and lower values of physical and mental health status compared to controls, while both groups showed a similar moderate physical activity level which can be assumed to counteract the negative effects of obesity or poor nutritional pattern in hidradenitis patients. However, none of the evaluated variables were correlated with the severity of the disease, assessed by means of the Hurley stage system or the Sartorius score. Instead, the Sartorius score showed a positive correlation with the duration of hidradenitis, mainly imputable to the diagnostic delay and the consequent long lasting inflammatory status. Although nutritional factors and lifestyle can be important and modifiable factors in the hidradenitis suppurativa course, the detrimental effect of chronic inflammation and delayed management are clearly prevalent and heavily influence the disease burden.


Morphologies, Young's Modulus and Resistivity of High Aspect Ratio Tungsten Nanowires.
High aspect ratio tungsten nanowires have been prepared by selective dissolution of Nickel-aluminum-tungsten (NiAl-W) alloys which were directionally solidified at growth rates varying from 2 to 25 μm/s with a temperature gradient of 300 K·cm-1. Young's modulus and electrical resistivity of tungsten nanowires were measured by metallic mask template method. The results show that the tungsten nanowires with uniform diameter and high aspect ratio are well aligned. The length of tungsten nanowires increases with prolongation of etching time, and their length reaches 300 μm at 14 h. Young's modulus of tungsten nanowires is estimated by Hertz and Sneddon models. The Sneddon model is proper for estimating the Young's modulus, and the value of calculating Young's modulus are 260-460 GPa which approach the value of bulk tungsten. The resistivity of tungsten nanowires is measured and fitted with Fuchs-Sondheimer (FS) + Mayadas-Shatzkes (MS) model. The fitting results show that the specific resistivity of W nanowires is a litter bigger than the bulk W, and its value decreases with decreasing diameter.


Prevalence of the Cusp of Carabelli: a systematic review and meta-analysis.
The Cusp of Carabelli (CoC) is the most commonly occurring dental morphological trait. To provide a pancontinental overview on the prevalence of the CoC in primary maxillary second molars and permanent maxillary molars. An electronic search was conducted on ten databases without year restrictions up to July 2020. All cross-sectional studies published in the English language reporting prevalence estimate of CoC were included. A modified version of the Newcastle-Ottawa scale was used to assess study quality. Meta-analyses were conducted for studies that reported data using Dahlberg and ASUDAS classification across continents. For qualitative synthesis, 142 studies (45,327 participants) were included, of which 130 studies had moderate risk of bias. Random effects meta-analysis was performed for 41 studies. For prevalence of CoC in primary maxillary second molars, the estimate was 72% (2,829 participants). The overall percentage attained for permanent maxillary molars was 59% (16,607 participants) for first molars; 8% (2,277 participants) for second molars; and 10% (89 participants) for third molars. Subgroup analysis revealed the European continent reported the highest prevalence in permanent maxillary first and second molars. Primary maxillary second molars recorded highest prevalence of CoC followed by permanent maxillary first, third and second molars. Pancontinental studies with regard to primary maxillary second molars are warranted.


Double mucosal and myocutaneous island flap: a one-stage reconstruction for full-thickness lower eyelid defect.
Basal cell carcinomas (BCCs) on the lower eyelid are not uncommon, and depending on their histological type, they can be highly aggressive and difficult to eradicate. Numerous techniques have been proposed for the reconstruction of the lower lid margin after surgical excision of the lesion. To describe a double-flap technique consisting of a mucosal and myocutaneous V-Y advancement flap to repair full-thickness lower lid margin defects in a one-stage procedure under local anesthesia. Over a 12-year period (1995-2007), 33 patients with BCC underwent lower eyelid reconstruction. After tumor excision, a triangular mucosal flap with a central pedicle was used to repair the inner layer. A similar triangular-shaped myocutaneous flap was obtained from the inferior orbicularis oculus muscle and sutured in a V-Y fashion to build the outer layer. All 33 patients achieved satisfactory functional and cosmetic results. Slight scleral show and discrete rounded lower eyelid were the main adverse effects. No additional surgery was needed. This double V-Y advancement flap is a simple, useful alternative procedure to close full-thickness defects in the lower lid margin. Aesthetic and functional outcome is good.


[Wilms tumor as a novel model of angiogenesis in childood nephropathies].
Wilms tumor has a unique possibility of recapitulation within its substance different stages of renal development. Vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1 and VEGFR-2) are regarded to play the crucial role in the process of simultaneous development of tubules and glomeruli in animal kidney. Neoangiogenesis, secondary to rearrangement of epithelial elements in Wilms tumor, may therefore follow the lack of glomeruli in this neoplasm. The aim of the present research was an immunohistochemical analysis of VEGF-C and VEGFR-2 expressions in Wilms tumor and an attempt of explanation of neovascularisation process in this malignancy. The study group was composed of 16 children diagnosed with Wilms tumor (stage III of clinical classification) hospitalised in Department of Paediatric Oncology, Hematology and Transplantology, University of Medical Sciences in Poznan. The indirect immunohistochemical assay with the use of monoclonal antibodies directed against VEGF-C and VEGFR-2 was employed. VEGF-C expression was detected within blastemal and hypocellular stromal components of Wilms tumor. On the other hand, immuno-reactivity of VEGFR-2 was established in dysplastic tubules in the closest proximity of VEGF-C positive parts of stromal origin. VEGF-C dependent neovascularisation in Wilms tumor may follow an adequate differentiation of already existing epithelial elements. It may also explain the process of glomeruli-dependent physiological development of kidney and, what is also probable, the phenomenon of neoangiogenesis described in individual childhood nephropathies.


[Application of gene gun for local-regional cancer].
We studied the in vivo gene transfusion using a gene gun, formerly used in plants and culture cells. The hand-held type gene gun (Helios Gene Gun System) is simple and convenient for effective gene transfection in living animals. This method has some advantages in that there is no need for use of viral vector, independence on the cell cycle and local inducement of plural genes. There is a great possibility for application to local-regional cancer.


Necessity of Distinguishing Verrucous Carcinoma From Verrucous Skin Lesion Overlaying Residual Skin Staples in an Area of Sensory Loss: A Case Report.
Verrucous skin lesions on the feet in diabetic neuropathy is a condition usually induced by chronic mechanical stimulation of the feet of patients with diabetic neuropathy and usually occurs at weight-bearing sites. We here present a rare case involving a man with verrucous skin lesions on the feet in diabetic neuropathy at an unusual, non-weight-bearing site. A 58-year-old man with diabetic neuropathy presented with a verrucous skin lesion overlaying residual skin staples and an amputation stump of the second metatarsal bone on the dorsal foot. The biopsy findings were inconclusive and suggested the necessity of distinguishing the lesion from verrucous carcinoma. The lesion was resected, and the residual skin staples were simultaneously removed. Investigation of the excisional biopsy confirmed our diagnosis of verrucous skin lesions on the feet in diabetic neuropathy. Verrucous skin lesions on the feet in diabetic neuropathy is often difficult to distinguish from verrucous carcinoma; in this case, the unusual location of the lesion could be attributed not only to sensory loss but also to the presence of an amputation stump and the persistence of the residual skin staples.


Guppy sexual behavior as an effect biomarker of estrogen mimics.
There is widespread concern that some environmental chemicals can reduce the reproductive capability of humans and wildlife by mimicking natural estrogens and disrupting endocrine function. This potential threat to animal populations posed by xenoestrogens has, hardly surprisingly, been met by an intensive global effort to identify and develop biomarkers suitable for screening chemicals for estrogen mimicking capacity. Despite this effort, there are few biomarkers capable of linking exposure to xenoestrogens to impaired reproductive capability. The reproductive success of most animals depends strongly on the ability to perform the appropriate sexual behavior. The sexual display of the male guppy is strongly linked to reproductive success and is readily quantified under laboratory conditions. This preliminary study demonstrates that exposure of adult male guppies to water weakly contaminated with either natural estrogen (17beta-estradiol) or the xenoestrogen (4-tert-octylphenol) causes a dramatic decrease in the rate and intensity of sexual display. It is concluded that quantitative analysis of the sexual display of male guppies holds great promise as a biomarker at the organismal level for the effects of estrogen mimicking xenobiotics.


Exploring Changes to the Actionability of COVID-19 Dashboards Over the Course of 2020 in the Canadian Context: Descriptive Assessment and Expert Appraisal Study.
Public web-based COVID-19 dashboards are in use worldwide to communicate pandemic-related information. Actionability of dashboards, as a predictor of their potential use for data-driven decision-making, was assessed in a global study during the early stages of the pandemic. It revealed a widespread lack of features needed to support actionability. In view of the inherently dynamic nature of dashboards and their unprecedented speed of creation, the evolution of dashboards and changes to their actionability merit exploration. We aimed to explore how COVID-19 dashboards evolved in the Canadian context during 2020 and whether the presence of actionability features changed over time. We conducted a descriptive assessment of a pan-Canadian sample of COVID-19 dashboards (N=26), followed by an appraisal of changes to their actionability by a panel of expert scorers (N=8). Scorers assessed the dashboards at two points in time, July and November 2020, using an assessment tool informed by communication theory and health care performance intelligence. Applying the nominal group technique, scorers were grouped in panels of three, and evaluated the presence of the seven defined features of highly actionable dashboards at each time point. Improvements had been made to the dashboards over time. These predominantly involved data provision (specificity of geographic breakdowns, range of indicators reported, and explanations of data sources or calculations) and advancements enabled by the technologies employed (customization of time trends and interactive or visual chart elements). Further improvements in actionability were noted especially in features involving local-level data provision, time-trend reporting, and indicator management. No improvements were found in communicative elements (clarity of purpose and audience), while the use of storytelling techniques to narrate trends remained largely absent from the dashboards. Improvements to COVID-19 dashboards in the Canadian context during 2020 were seen mostly in data availability and dashboard technology. Further improving the actionability of dashboards for public reporting will require attention to both technical and organizational aspects of dashboard development. Such efforts would include better skill-mixing across disciplines, continued investment in data standards, and clearer mandates for their developers to ensure accountability and the development of purpose-driven dashboards.


Molecular mechanisms of calcium-sensing receptor-mediated calcium signaling in the modulation of epithelial ion transport and bicarbonate secretion.
Epithelial ion transport is mainly under the control of intracellular cAMP and Ca(2+) signaling. Although the molecular mechanisms of cAMP-induced epithelial ion secretion are well defined, those induced by Ca(2+) signaling remain poorly understood. Because calcium-sensing receptor (CaSR) activation results in an increase in cytosolic Ca(2+) ([Ca(2+)]cyt) but a decrease in cAMP levels, it is a suitable receptor for elucidating the mechanisms of [Ca(2+)]cyt-mediated epithelial ion transport and duodenal bicarbonate secretion (DBS). CaSR proteins have been detected in mouse duodenal mucosae and human intestinal epithelial cells. Spermine and Gd(3+), two CaSR activators, markedly stimulated DBS without altering duodenal short circuit currents in wild-type mice but did not affect DBS and duodenal short circuit currents in cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice. Clotrimazole, a selective blocker of intermediate conductance Ca(2+)-activated K(+) channels but not chromanol 293B, a selective blocker of cAMP-activated K(+) channels (KCNQ1), significantly inhibited CaSR activator-induced DBS, which was similar in wild-type and KCNQ1 knockout mice. HCO3 (-) fluxes across epithelial cells were activated by a CFTR activator, but blocked by a CFTR inhibitor. CaSR activators induced HCO3 (-) fluxes, which were inhibited by a receptor-operated channel (ROC) blocker. Moreover, CaSR activators dose-dependently raised cellular [Ca(2+)]cyt, which was abolished in Ca(2+)-free solutions and inhibited markedly by selective CaSR antagonist calhex 231, and ROC blocker in both animal and human intestinal epithelial cells. Taken together, CaSR activation triggers Ca(2+)-dependent DBS, likely through the ROC, intermediate conductance Ca(2+)-activated K(+) channels, and CFTR channels. This study not only reveals that [Ca(2+)]cyt signaling is critical to modulate DBS but also provides novel insights into the molecular mechanisms of CaSR-mediated Ca(2+)-induced DBS.


Exposure to Tobacco Advertising and Promotion among School Children Aged 13-15 in Vietnam - an Overview from GYTS 2014.
Evidence shows that tobacco advertising and promotion activities may increase tobacco consumption and usage, especially in youth. Despite the regulation on prohibiting advertisement of any tobacco product, tobacco advertisement and promotion activities are still common in Vietnam. This article presents current exposure to tobacco advertising and promotion (TAP) among school children aged 13 to 15 years in Vietnam in 2014 and potential influencing factors. Data from the Global Youth Tobacco Survey 2014 in Vietnam covering 3,430 school aged children were used. Both descriptive and analytical statistics were carried out with Stata 13 statistical software. Binary logistic regression was applied to explain the exposure to TAP among youth and examine relationships with individual factors. A significance level of p<0.05 and sampling weights were used in all of the computations. In the past 30 days, 48.6% of the students experienced exposure to at least 1 type of tobacco advertising or promotion. Wearing or otherwise using products related to tobacco was the most exposure TAP type reported by students (22.3%). The internet (22.1), points of sales (19.2) and social events (11.5) were three places that students aged 13-15 frequently were exposed to TAP. Binary logistic results showed that gender (female vs male) (OR = 0.61, 95%CI: 0.52 - 0.71), susceptibility to smoking (OR = 2.12, 95%CI: 1.53 - 2.92), closest friends' smoked (OR = 1.43, 95%CI: 1.2 - 1.7) and parents smoking status (OR = 2.83, 95%CI: 1.6 - 5.01) were significantly associated with TAP exposure among school-aged children. The research findings should contribute to effective implementation of measures for preventing and controlling tobacco use among students aged 13-15 in Viet Nam.


Gene therapy for the hemophilias.
This review discusses the progress of gene therapy for the hemophilias. The development of gene therapy for hemophilia A has been more problematic than that for hemophilia B. It is now well established that reduced expression of the human clotting factor VIII cDNA is caused by transcriptional repression. Multiple sequences within the factor VIII cDNA are involved. So far, attempts to improve the factor VIII cDNA expression have been unsuccessful. However, improved retroviral vectors and adenovirus-based vectors have been constructed that increase factor VIII expression. The use of these vectors has resulted in clinically relevant levels of human factor VIII in mice and hemophilic dogs. Thus, gene therapy for hemophilia A has reached the same developmental stage as that for hemophilia B. If further improvements can increase the persistence of expression and decrease the immunologic responses, phase I clinical trials in human individuals can be considered.


Chronic indwelling bladder catheterization.
Chronic bladder catheterization is the treatment of last resort for incontinence. Urinary infection is a normal state in these patients. It should be treated only when there are signs of systemic illness. Accumulations of encrusted debris cause urinary leakage. This problem can be lessened by using silicone catheters and acidifying the urine. Urethritis is common, but catheters made of certain materials can reduce its severity. Bladder spasm can be treated pharmacologically.


Physaria fendleri and Ricinus communis lecithin:cholesterol acyltransferase-like phospholipases selectively cleave hydroxy acyl chains from phosphatidylcholine.
Production of hydroxy fatty acids (HFAs) in transgenic crops represents a promising strategy to meet our demands for specialized plant oils with industrial applications. The expression of Ricinus communis (castor) OLEATE 12-HYDROXYLASE (RcFAH12) in Arabidopsis has resulted in only limited accumulation of HFAs in seeds, which probably results from inefficient transfer of HFAs from their site of synthesis (phosphatidylcholine; PC) to triacylglycerol (TAG), especially at the sn-1/3 positions of TAG. Phospholipase As (PLAs) may be directly involved in the liberation of HFAs from PC, but the functions of their over-expression in HFA accumulation and distribution at TAG in transgenic plants have not been well studied. In this work, the functions of lecithin:cholesterol acyltransferase-like PLAs (LCAT-PLAs) in HFA biosynthesis were characterized. The LCAT-PLAs were shown to exhibit homology to LCAT and mammalian lysosomal PLA2 , and to contain a conserved and functional Ser/His/Asp catalytic triad. In vitro assays revealed that LCAT-PLAs from the HFA-accumulating plant species Physaria fendleri (PfLCAT-PLA) and castor (RcLCAT-PLA) could cleave acyl chains at both the sn-1 and sn-2 positions of PC, and displayed substrate selectivity towards sn-2-ricinoleoyl-PC over sn-2-oleoyl-PC. Furthermore, co-expression of RcFAH12 with PfLCAT-PLA or RcLCAT-PLA, but not Arabidopsis AtLCAT-PLA, resulted in increased occupation of HFA at the sn-1/3 positions of TAG as well as small but insignificant increases in HFA levels in Arabidopsis seeds compared with RcFAH12 expression alone. Therefore, PfLCAT-PLA and RcLCAT-PLA may contribute to HFA turnover on PC, and represent potential candidates for engineering the production of unusual fatty acids in crops.


Management of chronic stable angina pectoris.
Agina pectoris is a discomfort in the chest or adjacent areas caused by myocardial ischemia. It is most commonly caused by the inability of narrowed atherosclerotic coronary arteries to supply adequate oxygen to the heart under conditions of increase demand. This review article will focus in the medical treatment of chronic stable angina, with a focus in new strategies or medications. Treatment by revascularization techniques will not be discussed in this article. The goal of treatment is to improve quality of life, decrease cardiovascular events and mortality. All patients should be evaluated for reversible causes of their angina, such as anemia, hyperthyroidism, sympathomimetic drugs and hypertension. Sublingual nitroglycerin should be used for immediate relief of symptoms. In general, all patients should be on aspirin (ASA) unless they are allergic or other contraindications, if so; clopidogrel should be added to the therapy. In addition to the antiplatelet therapy, which decreases mortality, patients should be started on beta blockers and nitrates. If there is no improvement in symptoms then a calcium channel blockers of the dihydropyridine family should be added. Patients with Diabetes Mellitus and/or left ventricular systolic dysfunction should be also started on angiotensin converting enzyme inhibitors. If the patient continues with limiting angina, ranolazine should be started and finally enhanced external counterpulsation should be considered in those patients who have not responded to maximal drug therapy.


Reach and Effectiveness of Diabetes Self-Management Education and Support in a Network of Federally Qualified Health Centers.
Diabetes self-management education and support (DSMES) is an evidence-based intervention to improve diabetes-related outcomes. Access to DSMES is limited for diverse and low-income groups, despite greater need for services to address health disparities. Providing DSMES in federally qualified health centers (FQHCs) may increase reach for priority populations, and further study is needed to evaluate this delivery model. This report examines program effectiveness, including outcomes by race/ethnicity and Medicaid status, among 1,247 enrollees in FQHC-based DSMES. There was substantial glycated hemoglobin (A1c) improvement overall (-0.98%) among a diverse, majority-Medicaid population. However, Medicaid beneficiaries were approximately half as likely to attend as other enrollees (p<.001), while Latinx and non-Latinx Black participants attended fewer sessions (p=.008 and p=.040, respectively). Additionally, Medicaid beneficiaries experienced less A1c improvement than others (p=.040). Findings are promising that FQHC-based delivery can increase access to high-quality DSMES, although further effort appears needed to ensure optimal outcomes for all.


[Combination chemotherapy with gemcitabine and paclitaxel in a hemodialysis patient with metastatic urothelial carcinoma].
A 63-year-old man on hemodialysis for chronic renal failure developed a metastatic urothelial carcinoma and was treated with combination chemotherapies. For first line therapy, gemcitabine (GEM) and carboplatin (CBDCA) were given in combination. CBDCA was administered in a target area under the curve of 5.0 mg x min/ml according to the Calvert formula, followed by infusion of GEM at 1,000 mg/m(2), with hemodialysis started 1 hour after the end of CBDCA administration. Treatment-related adverse effects were severe, with grade 4 thrombocytopenia and neutropenia. Following two cycles of that therapy, partial response (PR) was obtained for lung metastasis, while progressive disease (PD) was noted in the liver. For second line therapy, GEM and paclitaxel (PAC) were given in combination. PAC was administered at 110 mg/m(2) before GEM at 1,000 mg/m(2) with hemodialysis given on the interval days. The adverse effect was grade 3 neutropenia, which was considered acceptable. After two cycles of second line therapy, PR was obtained for both lung and liver metastases, and maintained for 6 months. We concluded that GEM/PAC combination therapy is safe and effective for urothelial carcinoma patients undergoing concurrent hemodialysis.


What is the role of lipid A in the development of pyelonephritis? A hypothesis.
From the studies of Westenfelder et al. and our own studies of the presence of lipid A antibodies in the upper and lower urinary tract infections, it can be concluded that chronic pyelonephritis is a lipid A induced disease. This hypothesis is based on the distinct statistically different antibody production in upper urinary tract infection in contrast to lower urinary tract infection, the persistence of lipid A in renal tissue, as well as the induction of lipid A nephritis in puppies. These observations should be considered in future studies to proceed in the clarification of these diseases.


[Alcohol and epilepsy].
Epileptic seizures occur in 5-15% of individuals drinking alcohol. The majority are related to withdrawal, after heavy drinking, but these seizures may be indicative of an underlying structural disease, and always need diagnostic investigations. This type of fit does not require long term anticonvulsant therapy. More than 20% of newly diagnosed epilepsies in adults are alcoholic epilepsies, which concern less than 10% of alcoholic patients. Post-traumatic epilepsy is frequently intricate. Long term anticonvulsant therapy may be indicated, but is only possible if abstinence is acquired. Rare syndromes have been described, which specificity has not been demonstrated. Excessive drinking may provoke seizures in epileptics, whereas moderate or occasional use of alcohol may be not detrimental.


Development of an effluent discharge policy for the Tay Estuary based on a finite element model.
The tidal hydrodynamics and effluent distribution in estuaries involve a complicated range of solute transport phenomena modelled by partial differential equations. Therefore, the quantitative estimation of the risks of water and soil contamination of coastal areas as a result of polluted estuary flows, or effects of the effluent input on the chemical loads, involves the solution of these equations. Generally, the pollutants load in an estuary is determined by the nature of land use which by altering the watershed hydrology or chemical detention/release in the river banks affect the water quality of the estuaries. The present modelling work aims to investigate the solute transport behaviour in the Tay Estuary in Scotland. Based on this study, an attempt to devise an estuary specific discharge strategy for the Tay has been made. The numerical calculations are based on using 2D Galerkin finite element discretisation of the governing equations in an Eulerian co-ordinate system. The flexibility of the formulation allows it to be extended to moving boundary situations encountered in most tidal water systems.


Galectin-9 mediates neutrophil capture and adhesion in a CD44 and β2 integrin-dependent manner.
Neutrophil trafficking is a key component of the inflammatory response. Here, we have investigated the role of the immunomodulatory lectin Galectin-9 (Gal-9) on neutrophil recruitment. Our data indicate that Gal-9 is upregulated in the inflamed vasculature of RA synovial biopsies and report the release of Gal-9 into the extracellular environment following endothelial cell activation. siRNA knockdown of endothelial Gal-9 resulted in reduced neutrophil adhesion and neutrophil recruitment was significantly reduced in Gal-9 knockout mice in a model of zymosan-induced peritonitis. We also provide evidence for Gal-9 binding sites on human neutrophils; Gal-9 binding induced neutrophil activation (increased expression of β2 integrins and reduced expression of CD62L). Intra-vital microscopy confirmed a pro-recruitment role for Gal-9, with increased numbers of transmigrated neutrophils following Gal-9 administration. We studied the role of both soluble and immobilized Gal-9 on human neutrophil recruitment. Soluble Gal-9 significantly strengthened the interaction between neutrophils and the endothelium and inhibited neutrophil crawling on ICAM-1. When immobilized, Gal-9 functioned as an adhesion molecule and captured neutrophils from the flow. Neutrophils adherent to Gal-9 exhibited a spread/activated phenotype that was inhibited by CD18 and CD44 neutralizing antibodies, suggesting a role for these molecules in the pro-adhesive effects of Gal-9. Our data indicate that Gal-9 is expressed and released by the activated endothelium and functions both in soluble form and when immobilized as a neutrophil adhesion molecule. This study paves the way for further investigation of the role of Gal-9 in leukocyte recruitment in different inflammatory settings.


Chromosomal abnormalities in leiomyosarcomas.
Thirty-eight tumors from 30 patients diagnosed as leiomyosarcoma were cytogenetically assessed after short term culture. The specimens were obtained from the retroperitoneum, gastrointestinal tract, and extremities. Chromosomal abnormalities were present in 18 tumors from 13 patients; 15 tumors had clonal changes, whereas 3 tumors had numerous nonclonal changes. Ten tumors from 10 patients had normal karyotypes and no results were obtained in 10 other tumors from 7 patients. Of the tumors with clonal chromosomal aberrations, 4 had near-diploid (3 hypo- and one hyperdiploid) modes, 8 were polyploid, and 3 were bimodal. No specific karyotypic change appeared to characterize the leiomyosarcomas, although involvement of some chromosomes appeared more frequent than others. A comparison of our findings with those reported in the literature revealed certain consistent structural rearrangements involving chromosomes 1, 7, 10, 13, and 14 at bands 1p36, 1p32, 1p13, 1q32, 7p11.1-p21, 7q32, 10q22, 13q14, and 14p11, respectively. Other bands less frequently rearranged were 3p13-p22, 3q21, 4q13-q23, 6q15-q21, 7q11.2-q22, 12q13-q14, 17q12-q25, 19q13.3-q13.4, and 20q12-q13.1. Numerical changes included recurrent loss of chromosomes 4, 9, 14, 15, 16, 18, 21, and 22. Identification of the abnormalities of these chromosomes is important in that it may predict the existence of oncogenes, tumor suppressor genes, and/or growth factor genes at these sites. Subsequent molecular analysis might then lead to the identification of the genes involved and ultimately to a better understanding of the pathogenesis of leiomyosarcomas.


Hybrid vectors based on adeno-associated virus serotypes 2 and 5 for muscle-directed gene transfer.
Vectors based on hybrids consisting of adeno-associated virus types 2 (ITRs and Rep) and 5 (Cap) were evaluated for muscle-directed gene transfer (called AAV2/5). Evaluation in immune-competent mice revealed greater transduction efficacy with AAV2/5 than with AAV2 and no cross-neutralization between AAV2/5 and AAV2. Interestingly, we saw no immunologic evidence of previous exposure to AAV5 capsids in a large population of healthy human subjects.


[A new monoclonal antibody against human tubular brush border: preparation and its application in membranous nephropathy].
A new monoclonal antibody (McAb) against human tubular brush border was successfully prepared by authors using the hybridoma technique. The McAb produced was identified to be isotype of IgG1 by IF and SDS-PAGE assay. It was unique for its purity and specificity. To demonstrate the clinical usefulness, the McAb was applied for immunopathological study in 94 cases of renal biopsy of glomerular diseases. This McAb was distinguished by its specific deposition along the human tubular brush border and the subepithelial region in certain type of glomerular disease, particularly the MGN. Identification of this McAb might contribute to the immunopathological diagnosis of GN.


Healthcare reform and the hospital industry: what can we expect?
Healthcare costs continue to increase dramatically, while quality remains a significant problem. Reform measures adopted by Congress will fuel expansion of these costs, further stressing taxpayers and employers and forcing hospitals to adopt transformational changes as they adjust to increased demands for services and shrinking reimbursement. Cost control and quality improvement can be achieved through increased competition or greater government intervention. Competition will require unpalatable changes to the healthcare system to decrease costs without further restricting access or decreasing quality. Increased government intervention will result in changes to reimbursement and hospital-physician relations and increased demands for improved care. To improve cost and quality while preserving increased access, we advocate for a universal standard coverage of Americans; accountable healthcare system leadership; leverage of information resources to make utilization decisions and evaluate performance; alignment of physician, hospital, and payer incentives to focus on care outcomes rather than profit maximization; and the use of quasicompetition to allow for consumer choice within this system.


Relapsing polychondritis in childhood: three case reports, comparison with adulthood disease and literature review.
Relapsing polychondritis (RP) is a rare autoimmune systemic disease, especially in childhood. To report three new pediatric RP cases, to provide a literature review and to compare with adulthood disease, retrospective data collection from three childhood RP cases was observed in a Brazilian Pediatric Rheumatology Division. A literature review based on a MEDLINE database search was performed. Arthritis and auricular chondritis were present in our three patients. Two cases presented with early and severe laryngotracheal chondritis, besides initial and symptomatic costochondritis. The other case developed prominent epiphyseal plate involvement. Two patients were refractory to corticosteroids and immunosuppressants and required the use of TNF-alpha inhibitors to improve the symptoms, while corticosteroids plus methotrexate induced remission in the other patient. The literature review showed 44 cases of pediatric-onset disease in English language. Arthritis and ear chondritis are the most common initial and cumulative manifestations of RP in children and adults. Nasal and laryngotracheobronchial chondritis are also common manifestations observed during follow-up in childhood. There is also an early severity of respiratory chondritis in childhood, requiring aggressive treatment with corticosteroids, immunosuppressants and biologic agents. The data presented by those 3 children, considered in conjunction with the data from the 44 published cases, may reflect some distinguishing childhood RP features, such as more severe and frequent respiratory tract involvement, symptomatic costochondritis and the atypical pattern of persistent and destructive arthritis with epiphyseal plate involvement. Response to immunosuppressants and biologic agents is anecdotal, but steroids remain the main drug during the flares.


Structural basis for the barrier abnormality following inhibition of HMG CoA reductase in murine epidermis.
Recent studies have shown that increased epidermal 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase activity is crucial for the barrier recovery response that follows solvent-induced barrier perturbation. Upregulation of this enzyme leads to increased cholesterologenesis, formation and secretion of cholesterol-enriched lamellar bodies, and barrier repair. Topical lovastatin-induced inhibition of HMG CoA reductase activity both delays the acute barrier-repair response, as well as leading to a chronic barrier abnormality when applied repeatedly to intact skin. Presently, we assessed the effects of repeated topical applications of two different specific inhibitors of HMG CoA reductase on barrier function, the lamellar body-secretory system, and stratum corneum intercellular domains, with functional and morphologic parameters. Once-daily applications of lovastatin or fluindostatin (XU62-320; Sandoz) for 4-8 d to intact hairless mouse epidermis produced a progressive abnormality in barrier function (transepidermal water loss greater than 2.0-5.0 in treated versus less than 0.25 mg/cm2/h for weakly active analogues or vehicle controls). The barrier defect was preceded by alterations in lamellar body internal structure and a partial failure of lamellar body secretion into the stratum corneum interstices, further confirmed by enzyme cytochemistry. Moreover, the deposition of abnormal lamellar body contents resulted in the formation of clefts in the intercellular spaces at the stratum granulosum-stratum corneum interface, resulting in increased permeability through these domains shown by lanthanum perfusion. Applications of irritants, even when producing a barrier abnormality, did not alter the lamellar body secretory system. Co-applications of cholesterol with the inhibitors reversed both the barrier abnormality and the abnormalities in the lamellar body secretory system that occur with the inhibitor alone. Finally, membrane bilayer structures in the mid-to-outer stratum corneum of inhibitor-treated specimens appeared normal, but the intercellular domains displayed enormously expanded lacunae. However, because similar dilatations also occurred in vehicle-treated samples, they can be attributed to the vehicle alone. These studies provide further evidence that the inhibitor-induced defect in barrier function a) is initiated by inhibition of HMG CoA reductase; b) can be attributed to defects in both lamellar body structure and deposition with resultant abnormalities in intercellular membrane domains in the lower stratum corneum; and c) is further enhanced by permissive effects of the vehicle on the permeability of the outer stratum corneum.


Structural insights into binding of STAC proteins to voltage-gated calcium channels.
Excitation-contraction (EC) coupling in skeletal muscle requires functional and mechanical coupling between L-type voltage-gated calcium channels (CaV1.1) and the ryanodine receptor (RyR1). Recently, STAC3 was identified as an essential protein for EC coupling and is part of a group of three proteins that can bind and modulate L-type voltage-gated calcium channels. Here, we report crystal structures of tandem-SH3 domains of different STAC isoforms up to 1.2-Å resolution. These form a rigid interaction through a conserved interdomain interface. We identify the linker connecting transmembrane repeats II and III in two different CaV isoforms as a binding site for the SH3 domains and report a crystal structure of the complex with the STAC2 isoform. The interaction site includes the location for a disease variant in STAC3 that has been linked to Native American myopathy (NAM). Introducing the mutation does not cause misfolding of the SH3 domains, but abolishes the interaction. Disruption of the interaction via mutations in the II-III loop perturbs skeletal muscle EC coupling, but preserves the ability of STAC3 to slow down inactivation of CaV1.2.


Crystal structure of {(E)-4-[(1-allyl-1H-1,2,3-triazol-4-yl)meth-oxy]benzyl-idene}[2-(morpholin-4-yl)eth-yl]amine.
In the title compound, C19H25N5O2, the morpholine ring has a chair conformation. The plane of the central benzene ring makes dihedral angles of 88.75 (12) and 60.02 (7)°, respectively, with the mean plane formed by the four planar C atoms of the morpholine ring and with the plane of the triazole ring. In the crystal, mol-ecules are linked via C-H⋯π inter-actions, forming slabs lying parallel to (10-1). The C atoms of the bridging ethyl-ene group, between the morpholine and benzene rings, and the terminal ethene group of the prop-1-ene substituent attached to the triazole ring, are disordered over two sets of sites, with an occupancy ratio of 0.634 (13):0.366 (13).


Regioselective monosulfation and disulfation of the phytoestrogens daidzein and genistein by human liver sulfotransferases.
Regioselective sulfation of the phytoestrogens daidzein (DZ, 7,4'-dihydroxyisoflavone) and genistein (GS, 5,7,4'-trihydroxyisoflavone) was investigated using human liver cytosol and purified recombinant human sulfotransferase (SULT) isoforms, SULT1A1, SULT1A3, SULT2A1, and SULT1E1. 7-Position-preferential sulfation of DZ and GS was observed in human hepatic cytosols from 3 male and 3 female subjects. Average ratios for 7- to 4'-sulfate formation were 4.5:1 from DZ and 8.4:1 from GS in these human liver cytosols. Apparent K(m) values for the 7- and 4'-sulfation of DZ and GS by these cytosols were similar and in a range from 0.46 to 0.66 microM. All recombinant human SULTs had activity for 7- and 4'-sulfation of these phytoestrogens except for 7-sulfating activity of SULT1A3. SULT1A1 and SULT1E1 exhibited much higher catalytic efficiency, k(cat)/K(m), for 7- and 4'-sulfation of these substrates than did the other two, SULT1A3 and SULT2A1. SULT1A1 showed K(m) values of 0.47 and 0.52 microM for the mono-sulfation of DZ and GS, respectively, which were very similar to those of human cytosol. The observed k(cat)/K(m) indicated that SULT1A1 catalyzed 7-sulfation of DZ and GS at rates 4.4- and 8.8-fold higher, respectively, than such 4'-sulfation. However, with SULT1E1, catalytic efficiency was very similar for the sulfation of both positions. These data strongly suggest that SULT1A1 plays a major role in monosulfation of the phytoestrogens and determines the regioselectivity of sulfation in human hepatic cytosol. A kinetic study for 7,4'-disulfate formation of DZ and GS from their 7- and 4'-monosulfates indicated that SULT1E1 most efficiently catalyzed both reactions among human SULTs.


Natural family planning.
A better understanding of reproductive anatomy and physiology has led to newer methods of natural family planning, including the ovulation method and the symptothermal method. Studies have shown that 1 percent of couples who consistently and correctly use either of these methods conceives during one year of use. However, in the absence of standardized interpretation of study results, use-effectiveness data of these methods vary widely. The lactational amenorrhea method may be used in selected patients during the first six months postpartum, and its effectiveness in avoiding pregnancy is reported to be as high as 98 percent. Advocates of natural family planning promote these methods as inexpensive and safe ways to determine periods of peak fertility and point to the potential benefit of increased communication in a relationship.