Insulin secretion stimulated by allogeneic lymphocytes in an inbred strain of mice.
Effects of intraperitoneal injection of allogeneic lymphocytes on insulin secretion were studied in incubated pancreas slices from BALB/c mice. Injection of allogeneic lymphocytes from C57BL/6J (H2b) mice increased insulin secretion, both in basal and 11-mM glucose-stimulated conditions. This effect was only present when at least 5 X 10(6) or 1 X 10(6) cells were injected (in basal and stimulated conditions, respectively). Glucose-induced insulin secretion (3.3-27.5 mM) was significantly increased in pancreata from mice injected with allogeneic lymphocytes. No effect was observed when glucose was not included in the incubation medium. Intraperitoneal injection of Dextran 70 produced no change in glucose-elicited insulin secretion. There were no differences in glucagon and somatostatin (SRIF) secretion obtained from pancreas of mice injected with allogeneic or syngeneic lymphocytes. Injection of allogeneic cells increases insulin secretion (basal and both phases of 11 mM glucose-stimulated secretion). Puromycin significantly inhibited the second phase of insulin secretion. These results suggest that: Injection of allogeneic lymphocytes raises both basal and glucose-stimulated insulin secretion. This effect seems to be connected with the major histocompatibility complex, and to be related to the number of allogeneic cells injected. Injection of allogeneic lymphocytes seems to sensitize the beta cell response to glucose stimulus. Neither glucagon nor SRIF secretion are altered by alloantigen injection. The stimulatory effect of allogeneic lymphocytes is related, at least in part, to insulin synthesis.


Myocardial remodelling and recovery in dilated cardiomyopathy.
Myocardial reverse remodeling has been reported to occur in 25-70% of patients with dilated cardiomyopathy. It is not yet fully understood whether remodeling represents disease remission or cure and which hearts retain this capacity to recover. In this review article we discuss the capacity for recovery in DCM, the prognostic implications of this recovery and potential clinical and imaging predictors for myocardial remodeling.


Differential distribution of insulin-like growth factor-1 and insulin-like growth factor binding proteins in experimental diabetic rat kidney.
Insulin-like growth factor-1 (IGF-1) is a peptide growth factor, and its activity is modulated by interaction with the family of IGF binding proteins (IGFBP-1 to 6). IGF-1 is detected in rat kidney and has metabolic and growth effects. To explore the possible involvement of IGFBPs in glomerular hypertrophy in streptozotocin (STZ)-induced diabetic rat, the immunolocalization of IGF-1 and IGFBPs were investigated. IGF-1 was gradually increased in the glomeruli of diabetic rats and correlated with glomerular hypertrophy. IGFBP-1 was transiently increased at 1 week after the STZ injection and declined to control level during the following period. In contrast, IGFBP-4 was increased in the diabetic glomeruli throughout the observation period. With insulin treatment, the levels of IGF-1, IGFBP-1 and 4 were normalized and glomerular hypertrophy was prevented. Initial glomerular hypertrophy of diabetic nephropathy is a related IGF-1 action, which may be modulated by IGFBP-1 and 4.


The Galveston technique of pelvic fixation with L-rod instrumentation of the spine.
From April 1978 to October 1982, the authors performed 44 pelvic fixations as part of L-rod instrumentation of a spinal deformity. Thirty scoliosis and revision scoliosis cases with a minimum of 1 year follow-up were analyzed for changes of the instrumentation with respect to the pelvis, angular changes at the lumbosacral junction, radiolucency about the portions of the rods providing pelvic fixation, and success of lumbosacral fusion. The technique for fixation was different among three groups of patients. A pelvic fixation technique in which the pelvic segments of the rods were longer than 6 cm, completely intraosseous through their iliac course, and within 1.5 cm of the sciatic notch, yielded the best results.


In-hospital outcomes comparison of transfemoral vs transapical transcatheter aortic valve replacement in propensity-matched cohorts with severe aortic stenosis.
Transcatheter aortic valve replacement (TAVR) is the preferred option for high-risk patients with severe aortic stenosis. The preferred access for TAVR is transfemoral (TF). Alternatives include the transapical (TA), trans-subclavian (TS), and direct aortic (TAo) approaches. The TF approach is associated with lower in-hospital outcomes as well as shorter length of stay and lower cost of hospitalization. The National Inpatient Sample database from 2012 through 2014 was used to obtain the TAVR study population. International Classification of Diseases, 9th Revision, Clinical Modification procedure codes were utilized to identify the 2 groups. In-hospital outcomes were compared in propensity-score-matched (1:3) cohorts, in which we took TA-TAVR as a control. A total of 8210 (weighted N = 41 050) patients were identified. Of these, 1622 (weighted N = 8110) patients underwent TA-TAVR and 6588 (weighted N = 32 940) patients underwent TF-TAVR. In-hospital mortality was lower with TF-TAVR (4% vs 5.4%; P = 0.0355), along with a shorter length of stay (7.7 vs 9.7 days; P < 0.0001) and lower median hospitalization cost ($64 216 vs $74 735; P < 0.0001). Secondary outcomes of acute renal failure, transfusion, cardiogenic shock, and composite of all complications were lower with TF-TAVR. TF-TAVR is safer and associated with lower in-hospital outcomes compared with TA-TAVR and should be the preferred approach. As TAVR is gaining popularity in intermediate- and low-risk patients, we must not lose sight of the serious mortality and secondary outcomes associated with TA-TAVR access.


ChickRH6: a chicken whole-genome radiation hybrid panel.
As a first step towards the development of radiation hybrid maps, we have produced a radiation hybrid panel in the chicken by fusing female embryonic diploid fibroblasts irradiated at 6,000 rads with HPRT-deficient hamster Wg3hCl2 cells. Due to the low retention frequency of the chicken fragments, a high number of clones was produced from which the best ones were selected. Thus, 452 fusion clones were tested for retention frequencies with a panel of 46 markers. Based on these results, 103 clones with a mean marker retention of 23.8% were selected for large scale culture to produce DNA in sufficient quantities for the genotyping of numerous markers. Retention frequency was tested again with the same 46 markers and the 90 best clones, with a final mean retention frequency of 21.9%, were selected for the final panel. This panel will be a valuable resource for fine mapping of markers and genes in the chicken, and will also help in building BAC contigs.


Cigarette Smoke Triggers IL-33-associated Inflammation in a Model of Late-Stage Chronic Obstructive Pulmonary Disease.
Chronic obstructive pulmonary disease (COPD) is a worldwide threat. Cigarette smoke (CS) exposure causes cardiopulmonary disease and COPD and increases the risk for pulmonary tumors. In addition to poor lung function, patients with COPD are susceptible to bouts of dangerous inflammation triggered by pollutants or infection. These severe inflammatory episodes can lead to additional exacerbations, hospitalization, further deterioration of lung function, and reduced survival. Suitable models of the inflammatory conditions associated with CS, which potentiate the downward spiral in patients with COPD, are lacking, and the underlying mechanisms that trigger exacerbations are not well understood. Although initial CS exposure activates a protective role for vascular endothelial growth factor (VEGF) functions in barrier integrity, chronic exposure depletes the pulmonary VEGF guard function in severe COPD. Thus, we hypothesized that mice with compromised VEGF production and challenged with CS would trigger human-like severe inflammatory progression of COPD. In this model, we discovered that CS exposure promotes an amplified IL-33 cytokine response and severe disease progression. Our VEGF-knockout model combined with CS recapitulates severe COPD with an influx of IL-33-expressing macrophages and neutrophils. Normally, IL-33 is quickly inactivated by a post-translational disulfide bond formation. Our results reveal that BAL fluid from the CS-exposed, VEGF-deficient cohort promotes a significantly prolonged lifetime of active proinflammatory IL-33. Taken together, our data demonstrate that with the loss of a VEGF-mediated protective barrier, the CS response switches from a localized danger to an uncontrolled long-term and long-range, amplified, IL-33-mediated inflammatory response that ultimately destroys lung function.


Protective efficacy of naringenin against cadmium-induced redox imbalance in Labeo rohita: an integrated biomarker approach.
The protective efficacy of dietary naringenin (NG) has been investigated against the toxicity caused by cadmium chloride (CdCl2) using biomarkers of oxidative stress in the liver, gills and kidney of Labeo rohita. The fish were exposed to environmentally relevant concentrations of CdCl2 (0.37 and 0.62 mg/L) and simultaneously orally administered with NG (50 mg/kg bw/day) for 60 days. Tissue (gills, liver and kidney) samples were collected on days 15, 30 and 60 of the experiment and analysed for endogenous antioxidants and oxidative stress biomarkers. CdCl2 exposure for 15 and 30 days induced the development of adaptive mechanism as demonstrated by the enhanced activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in all three tissues. However, on the 60th day, CdCl2-induced oxidative damage was stipulated by a decline in the enzyme activities and reduced glutathione (GSH) content significantly (p < 0.05) below control levels along with enhanced levels of lipid peroxidation. Oral administration of NG in toxicant exposed fish significantly restored the altered levels of antioxidants, oxidative enzymes and lipid peroxidation. Besides, integrated biomarker response (IBR) analysis was applied by combining all the biomarkers to indicate the overall stress response index. IBR analysis confirmed the altered levels of biomarkers, the oxidative stress induced by CdCl2 exposure and the ameliorative potential of NG. The present study suggested that NG might have protective role against Cd-induced oxidative insult which might be ascribed to the ability of NG to chelate metals and scavenge free radicals.


Large local deflections of a dynamic crack front induced by intrinsic dislocations in brittle single crystals.
We show that intrinsic dislocations in brittle single crystals can be a source of strong local perturbations along the crack path. A theoretical model was developed which predicts substantial crack front deflections. Investigating the crack surfaces in Si crystals with induced dislocation density of 10(9)-10(10) cm(-2) revealed a significant amount of crack front perturbations in the form of V-shaped grooves, which were completely missing in dislocation-free Si specimens. The measured depths of the perturbations were in the range of 2-20 nm and in excellent agreement with the theoretical model.


Comparative effects of ageing and dementia of the Alzheimer type on orientation of visual attention.
Age-related changes and the effects of dementia of the Alzheimer type (DAT) were investigated during a visual orienting attention task in which attention was pre-cued to one or other hemifields. Central cues were either valid, neutral, invalid or NoGo (inhibitory). The response time cost-benefit analysis showed a decreased benefit after valid cueing in the old compared with the young group with no change in the cost of invalid cueing. The older group were also slower over all cue types. These results suggest there is an age-related reduced ability to covertly orient attention in a visual hemifield before target onset. In contrast, the DAT group showed an increased response time benefit and showed a trend for a decreased cost in response time compared with controls. This was due to slowest response times after neutral cues. They also made significantly more response errors particularly following neutral cueing, and were less able to inhibit responses on NoGo trials than controls. The increased benefit and reduced cost found in the DAT group was interpreted as an impairment in dividing attention between left and right target locations.


Development of Carbon Nanostructured Based Electrochemical Sensors for Pharmaceutical Analysis.
Pharmaceutical drugs play an important role in human life since they caused a revolution in human health. Notably, their administration to a living organism helps body to stay healthy. Commonly, they are employed to diagnose, prevent, or treat and cure a disease via a biological effect on a human body. Administration of impurity-free and adequate amounts of pharmaceutical compounds would be beneficial. Therefore, the quantity and purity of the substances in pharmaceutical compounds are continuously monitored during drug manufacturing with various chemical or instrumental analysis techniques. The possibility of impurities development and chemical or quantity changes of active drug species at various stages (namely during production, transportation or storage) makes them redundant and risky for human health. So, sensitive and accurate analysis methods for qualitative and quantitative analysis are highly demanded by pharmaceutical companies and medical centers. The present mini review emphasizes on application of carbon based modified electrodes in health care and pharmaceutical analysis. Electrochemical determination of drugs employing carbon nanostructured modified electrodes will be reviewed and their advantages and disadvantages will be mentioned.


Nuclear magnetic resonance spectroscopy in glutaryl-CoA dehydrogenase deficiency.
Nuclear magnetic resonance (NMR) spectroscopy is a safe, noninvasive method that is the preferred technique for in vivo analysis of specific chemical compounds in localized brain regions. Besides quantification of compounds, NMR spectroscopy allows the detailed analysis of neurotransmitter, glucose and lactate metabolism following peripheral infusions of stable isotopically labelled precursors. The latter has been successfully applied to patients with different neurological disease states not including glutaryl-CoA dehydrogenase (GCDH) deficiency. In contrast, single patients with GCDH deficiency who were neurologically unremarkable have been studied with conflicting results. One patient was shown to have an increase in intracerebral creatine and phosphocreatine concentrations, while the second studied had unremarkable levels. In a 15-year-old patient, we were able to demonstrate elevated levels of intracerebral lactate and elevated choline/N -acetylaspartate ratios, indicating potentially increased myelin turnover and reduced neuronal integrity in periventricular white matter. Interestingly, spectra in basal ganglia were within normal limits. Systematic studies to address well-defined questions in GCDH deficiency are urgently needed. In particular, analysis of in vivo neurotransmitter metabolism following administration of isotopically labelled precursors in patients with GCDH deficiency, both when metabolically stable and when unstable, may help to advance our understanding of the pathophysiology of GCDH deficiency.


[Postpartum depression: prevalence and associated factors].
The aim was to identify the prevalence of postpartum depression and associated factors in women in a medium-sized city in Southern Brazil during 2013. Trained female interviewers applied a standardized questionnaire to all participants in the city's two maternity hospitals. The study analyzed demographic, socioeconomic, behavioral, social support, and disease characteristics. Screening for depression was done within the first 48 hours postpartum, using the Edinburgh Scale with a cutoff of ≥ 10. Multivariate analysis used Poisson regression with robust variance. Of the 2,687 women interviewed, 14% (95%CI: 12.9-15.6) were identified with depression. Factors such as previous depression, third-trimester sadness, and family history of depression were associated with increased risk of postpartum depression, as were younger maternal age and multiparity. Social support from the health team for the pregnant woman was an important protective factor, reducing the prevalence of postpartum depression by 23%. The results suggest the need for actions by health services for pregnant women in order to provide enhanced care during this delicate phase.


Analysis of Chromophytic and Rhodophytic Ribulose-1,5-Bisphosphate Carboxylase Indicates Extensive Structural and Functional Similarities among Evolutionarily Diverse Algae.
Ribulose-1,5-bisphosphate carboxylase (Rubisco) from the algae Olisthodiscus luteus (chromophyte) and Griffithsia pacifica (rhodophyte) are remarkably similar to each other. However, both enzymes differ significantly in the structure and function when compared to Rubisco from green algae and land plants. Analysis of purified Rubisco from O. luteus and G. pacifica indicates that the size of the holoenzyme and stoichiometry of the 55 and 15 kilodalton subunit polypeptides are approximately 550 kilodaltons and eight:eight for both algae. Antigenic determinants are highly conserved between the O. luteus and G. pacifica enzymes and differ from those of the spinach subunit polypeptides. Sequence similarity between the two algal large subunits has been further confirmed by one-dimensional peptide mapping. Substrate ribulose bisphosphate has no effect on the rate of CO(2)/Mg(2+) activation of O. luteus and G. pacifica enzymes which contrasts to the extensive inhibition of spinach Rubisco activation at similar concentrations of this compound. In addition, the Michaelis constant for CO(2) and the inhibition constant for 6-phosphogluconate are similar for the O. luteus and G. pacifica catalyzed carboxylation reaction. Both values are intermediate to those observed for the tight binding spinach enzyme and weak binding prokaryotic (Rhodospirillum rubrum) enzyme. The biochemical similarities documented between O. luteus and G. pacifica may be due to a common evolutionary origin on the chromophytic and rhodophytic chloroplast but could also result from the fact that both subunit polypeptides are chloroplast DNA encoded in these algal taxa.


[Dyssegmental dysplasia. Apropos of 2 familial cases with fatal development].
The authors report the cases of 2 sisters presenting with dyssegmental dwarfism. There were 2 other girls in the siblings, one of which was most probably also concerned. These cases favor a recessive transmission of the disease which, thereby, should not be confused with Kniest's disease, as suggested by some authors.


Decree No. 18105-RENEM-H of 28 April 1988.
This Decree amends certain articles of Decree No. 16986-MAG of 7 May 1986 to regulate more adequately all reforestation activities and to develop them through state incentives. Modified sections establish payments that can be solicited by persons after presenting a reforestation plan for land that they own. They also describe application procedures, steps that the Government of Costa Rica must take before approving plans, the manner in which payments are made on a yearly basis, amounts to be paid per hectare per year, requirements of compliance with general forestry laws, and special payments that can be made to the owners of small parcels of land whose income does not exceed a certain level.


Modal Properties of Photonic Crystal Cavities and Applications to Lasers.
Photonic crystal cavities enable strong light-matter interactions, with numerous applications, such as ultra-small and energy-efficient semiconductor lasers, enhanced nonlinearities and single-photon sources. This paper reviews the properties of the modes of photonic crystal cavities, with a special focus on line-defect cavities. In particular, it is shown how the fundamental resonant mode in line-defect cavities gradually turns from Fabry-Perot-like to distributed-feedback-like with increasing cavity size. This peculiar behavior is directly traced back to the properties of the guided Bloch modes. Photonic crystal cavities based on Fano interference are also covered. This type of cavity is realized through coupling of a line-defect waveguide with an adjacent nanocavity, with applications to Fano lasers and optical switches. Finally, emerging cavities for extreme dielectric confinement are covered. These cavities promise extremely strong light-matter interactions by realizing deep sub-wavelength mode size while keeping a high quality factor.


[Development of standard gas mixture of chlorinated hydrocarbons in nitrogen].
A method for the preparation of the standard gas mixture of 6 chlorinated hydrocarbons, containing dichloromethane, 1,1-dichloroethane, 1,2-dichloroethane, chloroform, 1,1, 1-trichloroethane, and 1,1,2-trichloroethane, at the concentration of 5 micromol/mol in nitrogen was developed. The reproducibility of this method and the homogeneity and long-term stability of the standard mixture were evaluated. The results showed that all 6 chlorinated hydrocarbons have shown stability as long as 12 months and the expanded relative uncertainty of 5%. The certified value of developed standard gas agreed with the similar standard gas from Scott Specialty Gases. This research established a foundation for the analysis of volatile chlorinated hydrocarbon gases.


Six new metabolites produced by Colletotrichum aotearoa 09F0161, an endophytic fungus isolated from Bredia oldhamii.
Six new compounds, colletobredins A-D (1-4) and colletomelleins A and B (5 and 6), along with 12 previously identified compounds, were isolated from the culture broth of Colletotrichum aotearoa BCRC 09F0161, a fungal endophyte residing in the leaves of an endemic Formosan plant Bredia oldhamii Hook. f. (Melastomataceae). The structures of the new compounds were established by spectroscopic methods, including UV, IR, HR-ESIMS and extensive 1D and 2D NMR techniques. The effects of some isolates on the inhibition of nitric oxide (NO) production in lipopolysaccharide-activated murine macrophage RAW264.7 cells were evaluated. All these compounds inhibited NO production in activated macrophages without any cytotoxicity at a concentration of 100 μM. Of these isolates, 1 showed weak NO inhibitory activity with IC50 value of 182.2 μM. To the best of our knowledge, this is the first report on isochroman glycoside metabolites (1-4) from the genus Colletotrichum.


Tendon collagens: extracellular matrix composition in shear stress and tensile components of flexor tendons.
Outer synovial tissues were separated from the remainder of avian flexor tendon and the collagens characterized biochemically and compared with those of the internal portion of tendon and sheath. The collagen content of tendon synovium was 23%, whereas that of tendon and sheath were 78% and 73%, respectively, based on dry weight. Four genetic types of collagen were found in the pepsin solubilized matrices: in the synovium, types I (78%) and III (19%) predominated; types V and possibly VI were present as minor collagens. Purified synovial type V collagen was a heterotrimer, with chain composition [alpha 1(V)]2 alpha 2(V). In contrast, the internal portion of tendon and sheath were comprised of only type I collagen. There was a large amount (41%) of ethanol extractable, noncollagenous material present in synovium, a part of which was proteoglycans. In addition, collagen cross-links of these tissues were quantified: the internal tendon had an abundant concentration of pyridinoline; synovium exhibited high amounts of labile, reducible cross-links, particularly dihydroxylysinonorleucine. In the case of sheath, lysine aldehyde-derived cross-links appeared to be predominant. These results indicate that each tissue has its own collagen type distribution as well as cross-linking pattern reflecting their maturational and functional differences.


Mitogen-activated protein kinase 5, a novel molecular marker for the identification and detection of Trypanozoon species.
Based on the sequence of mitogen-activated protein kinase 5 (TbMAPK5) gene, we have developed a specific PCR method which can delineate the species within the Trypanozoon subgenus from other parasites or host DNA conveniently. In view of further application in field studies, we performed loop-mediated isothermal amplification (LAMP) employing filter paper flecked with rodent blood. Our data showed that TbMAPK5-specific LAMP was sensitive enough to detect a very low parasitemia during the early stages of the infection and fluctuating parasitemia period, and is below the detection limit by microscope. The detection limit for the infected blood sample was 1000 trypanosomes/ml of blood. Based on these results, we consider that TbMAPK5 locus may be a useful target for LAMP diagnosis providing sensitivity and the potential for the genotyping/identification of Trypanozoon species.


Low plasma cyclic nucleotides in multiple sclerosis.
The concentrations of cyclic AMP and cyclic GMP were estimated in plasma of 26 patients with definite multiple sclerosis (MS) in relapse, and compared to that of 26 sex- and age-matched healthy controls. MS patients had significantly lower levels of both nucleotides. The levels of c-GMP correlated negatively to the Disability Status Scale score.


Radiofrequency-Assisted Partial Splenectomy Plus Splenopexy--A Modified Surgical Procedure for Wandering Spleen: A Case Report.
Wandering spleen is an extremely rare clinical condition characterized by abnormal anatomical position of the spleen. Up to now, its etiology remains unknown, and the best surgical procedure is still an area to explore in the future. In this article, we present the case of a 24-year-old woman with wandering spleen combined with congenital heart disease and pigeon chest. Based on the clinical features and our experiences of radiofrequency ablation for preservation of the spleen in traumatic spleen rupture, we successfully performed a modified splenectomy and splenopexy method. Since the operation, the organ has remained in place with good perfusion and function.


Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood.
Prenatal arsenic exposure is associated with increased risk of disease in adulthood. This has led to considerable interest in arsenic's ability to disrupt fetal programming. Many studies report that arsenic exposure alters DNA methylation in whole blood but these studies did not adjust for cell mixture. In this study, we examined the relationship between arsenic in maternal drinking water collected ≤ 16 weeks gestational age and DNA methylation in cord blood (n = 44) adjusting for leukocyte-tagged differentially methylated regions. DNA methylation was quantified using the Infinium HumanMethylation 450 BeadChip array. Recursively partitioned mixture modeling examined the relationship between arsenic and methylation at 473,844 CpG sites. Median arsenic concentration in water was 12 µg/L (range<1- 510 µg/L). Log 10 arsenic was associated with altered DNA methylation across the epigenome (P = 0.002); however, adjusting for leukocyte distributions attenuated this association (P = 0.013). We also observed that arsenic had a strong effect on the distribution of leukocytes in cord blood. In adjusted models, every log 10 increase in maternal drinking water arsenic exposure was estimated to increase CD8+ T cells by 7.4% (P = 0.0004) and decrease in CD4+ T cells by 9.2% (P = 0.0002). These results show that prenatal exposure to arsenic had an exposure-dependent effect on specific T cell subpopulations in cord blood and altered DNA methylation in cord blood. Future research is needed to determine if these small changes in DNA methylation alter gene expression or are associated with adverse health effects.


Predation risk and space use of a declining Dall sheep (Ovis dalli dalli) population.
The abundance of ungulate populations may fluctuate in response to several limiting factors, including climate, diseases, and predation. In the northern Richardson Mountains, Canada, Dall sheep (Ovis dalli dalli) have undergone a major decline in the past decades and predation by grizzly bears (Ursus arctos) and wolves (Canis lupus) was suspected as a leading cause. To better understand the relationship between these three species located in this rugged and remote ecosystem, we relied on a combination of indirect methods. We investigated the apparent role of predation on the Dall sheep population using spatial ecology and stable isotopes. We examined seasonal variation in predation risk, focusing on how it may affect Dall sheep habitat use and sexual segregation, and we evaluated the proportion of Dall sheep in the diet of both predators using stable isotopes. The movements of the three species were monitored by satellite telemetry. Dall sheep habitat use patterns were analyzed using topographical features, greenness index, land cover, and apparent predation risk. The diets of grizzly bears and wolves were examined using a Bayesian mixing model for carbon and nitrogen stable isotopes. We found that Dall sheep habitat use varied seasonally, with different patterns for ewes and rams. Exposure to grizzly bear risk was higher for rams during summer, while ewes were further exposed to wolf apparent predation risk during winter. The importance of safe habitats for ewes was reflected in space use patterns. Stable isotopes analyses suggested that the diet of grizzly bears was largely from animal sources, with mountain mammals comprising about one quarter. Wolves mostly fed on both aquatic browsers and mountain mammals. Diet variation between individual predators suggested that some individuals specialized on mountain mammals, likely including Dall sheep. We conclude that grizzly bear and wolf apparent predation risk are important in driving Dall sheep habitat use and play a role in sexual segregation. Overall, this study presents an innovative combination of indirect methods that could be applied elsewhere to better understand predator-prey dynamics in remote ecosystems.


Use of ambulatory physician group clinical information by hospital-based users within an integrated delivery network.
At Intermountain Healthcare, as part of a broad information system transition plan, a proposal was made to replace the integrated ambulatory EHR, used by 550 physicians, with a new stand alone EHR. The notion leading to the proposal was that ambulatory data was infrequently accessed outside of the ambulatory setting. To test this notion, retrospective analysis was done to determine the number of ambulatory patient events accessed by hospital based users. 399 Departments from the Hospital-based group accessed 1, 984, 785 patient events that originated from within the ambulatory group in a 90 day period. This study showed that a significant number of ambulatory patient records were viewed by a wide range of hospital-based users. The decision to replace the legacy ambulatory system with a new, stand alone system was postponed. This analysis was critical in planning the road map for a new integrated clinical information system.


Changes in pulmonary functional parameters after surgical treatment of idiopathic scoliosis.
There is a controversy in results about influence of surgery on pulmonary function in idiopathic scoliosis. The aim of the study was to study pulmonary function in severe thoracic idiopathic scoliosis and to detect changes in pulmonary function after the three-dimensional anterior surgical correction in severe thoracic scoliosis. 91 patients at the age of 16 +/- 5.1 yrs underwent surgery in order to make a correction of scoliotic deformity. All the curves were greater than 70 degrees (86 +/- 5.1). Group I consisted of 60 patients with scoliotic curves between 70 degrees and 100 degrees, while group II consisted of 31 patients with curves greater than 100 degrees. All the patients were operated by anterior instrumentation and the average correction was 74% +/- 15 for group I, and 71% +/- 18 for group II. Vital capacity (VC) and forced expiratory volume in the first second (FEV1) in group I remained unchanged. In group II, VC improved for 11%, while forced expiratory volume (FEV) improved for 13.6%. Our conclusion is that there is a significant correlation between the percentage of achieved correction and pulmonary function.


Phylogenetic relationships of the Canary Islands endemic lizard genus Gallotia (Sauria: Lacertidae), inferred from mitochondrial DNA sequences.
Phylogenetic relationships among species and subspecies of the Canary Island endemic lizard genus Gallotia are inferred based on nucleotide sequences of fragments of 12S ribosomal RNA and cytochrome b mitochondrial genes. The four morphologically established species have also been recognized at the molecular level. Relative affinities among species follow an eastern-western geographic transect. The nearly extinct species Gallotia simonyi from the most western island of El Hierro is closely related to the common western species Gallotia galloti, the nearest branch to this pair is Gallotia stehlini from the central island of Gram Canaria, and finally, Gallotia atlantica from the two eastern and geologically oldest islands appears as the most distantly related species of the group. At the statistical level, four subspecies can be recognized in G. galloti, but only two in G. atlantica.


Genome Sequence of the Fish Pathogen Yersinia ruckeri SC09 Provides Insights into Niche Adaptation and Pathogenic Mechanism.
Yersinia ruckeri is the etiologic agent of enteric red mouth disease (ERM), a severe fish disease prevailing in worldwide aquaculture industries. Here we report for the first time the complete genome of Y. ruckeri (Yersinia ruckeri) SC09, a highly virulent strain isolated from Ictalurus punctatus with severe septicemia. SC09 possesses a single chromosome of 3,923,491 base pairs, which contains 3651 predicted protein coding sequences (CDS), 19 rRNA genes, and 79 tRNA genes. Among the CDS, we have identified a Ysa locus containing genes encoding all the components of a type III secretion system (T3SS). Comparative analysis suggest that SC09-Ysa share extensive similarity in sequence, gene content, and gene arrangement with Salmonella enterica pathogenicity island 1 (SPI1) and chromosome-encoded T3SS from Yersinia enterocolitica biotype 1B. Furthermore, phylogenetic analysis shown that SC09-Ysa and SPI1-T3SS belong on the same branch of the phylogenetic tree. These results suggest that SC09-Ysa and SPI1-T3SS appear to mediate biological function to adapt to specific hosts with a similar niche, and both of them are likely to facilitate the development of an intracellular niche. In addition, our analysis also indicated that a substantial part of the SC09 genome might contribute to adaption in the intestinal microenvironment, including a number of proteins associated with aerobic or anaerobic respiration, signal transduction, and various stress reactions. Genomic analysis of the bacterium offered insights into the pathogenic mechanism associated with intracellular infection and intestinal survivability, which constitutes an important first step in understanding the pathogenesis of Y. ruckeri.


Pathology of the pituitary gland in patients with the acquired immune deficiency syndrome (AIDS).
The pituitary gland was examined at autopsy in 88 patients who died with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC). Pathologic findings included focal to widespread necrosis and/or fibrosis of the anterior pituitary gland in 10 cases, evidence of cytomegalovirus infection without an apparent inflammatory component in the anterior pituitary in 3 cases, and microglial nodules in the pars nervosa in 5 cases. In one instance, a multinucleated giant cell identical to those associated with direct human immunodeficiency virus infection of brain was identified in the pars nervosa. One patient showed focal anterior pituitary infection by Cryptococcus neoformans in the context of widespread and severe cryptococcosis. These findings are discussed in relation to the possible clinical manifestations and the neuropathologic and systemic pathologic findings in AIDS patients.


Strain Measurement in Aluminium Alloy during the Solidification Process Using Embedded Fibre Bragg Gratings.
In recent years, the observation of the behaviour of components during the production process and over their life cycle is of increasing importance. Structural health monitoring, for example of carbon composites, is state-of-the-art research. The usage of Fibre Bragg Gratings (FBGs) in this field is of major advantage. Another possible area of application is in foundries. The internal state of melts during the solidification process is of particular interest. By using embedded FBGs, temperature and stress can be monitored during the process. In this work, FBGs were embedded in aluminium alloys in order to observe the occurring strain. Two different FBG positions were chosen in the mould in order to compare its dependence. It was shown that FBGs can withstand the solidification process, although a compression in the range of one percent was measured, which is in agreement with the literature value. Furthermore, different lengths of the gratings were applied, and it was shown that shorter gratings result in more accurate measurements. The obtained results prove that FBGs are applicable as sensors for temperatures up to 740 °C.


Detrimental effects of BOLD signal in arterial spin labeling fMRI at high field strength.
Arterial spin labeling (ASL) MRI is a useful technique for noninvasive measurement of cerebral blood flow (CBF) in humans. High field strength provides a unique advantage for ASL because of longer blood T(1) relaxation times, making this technique a promising quantitative approach for functional brain mapping. However, higher magnetic field also introduces new challenges. Here it is shown that the CBF response determined using ASL functional MRI (fMRI) at 3.0 T contains significant contamination from blood-oxygenation-level-dependent (BOLD) effects. Due to interleaved acquisitions of label and control images, difference in blood oxygenation status between these two scans can cause incomplete cancellation of the static signal upon image subtraction, resulting in a BOLD-related artifact in the estimated CBF hemodynamics. If not accounted for, such an effect can complicate the interpretation of the ASL results, e.g., causing a delayed onset and offset of the response, or inducing an artifactual poststimulus undershoot. The BOLD contribution also decreases the sensitivity of ASL-based fMRI. Correction methods are proposed to reduce the artifact, giving increased number of activated voxels (18+/-5%, P=0.006) and more accurate estimation of CBF temporal characteristics.


Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cells.
Aloperine (ALO), an alkaloid isolated from the leaves of Sophora alopecuroides, has been suggested to exhibit anti-inflammatory and anti-tumor properties and is traditionally used to treat various human diseases, including cancer. However, limited information is available about the mechanisms that determine the anti-tumor activities of ALO. Herein, through comprehensive bioinformatics methods and in vitro functional analyses, we evaluated the detailed anti-tumor mechanisms of ALO. Using the databases Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine and PubChem Project, we identified the potential targets of ALO. A protein-protein interaction network was constructed to determine the relationship among these probable targets. Functional enrichment analysis revealed that ALO is potentially involved in the induction of apoptosis. In addition, molecular docking demonstrated that ALO expectedly docks into the active pocket of the Bcl2 protein, suggesting Bcl2 as a direct target of ALO. Moreover, western blot and qPCR analysis showed that ALO downregulated Bcl2 expression in human glioma cell lines, SK-N-AS and U118. Using flow cytometry methods, we further confirmed that ALO significantly promotes apoptosis in SK-N-AS and U118 cell lines, similar to the effect induced by ABT-737, a well-known Bcl2 inhibitor. In addition, Bcl-2 overexpression could rescue ALO-induced Bcl-2 inhibition and suppress pro-apoptotic effects in glioma cells. Taken together, these findings suggest that the natural agent ALO effectively enhances apoptosis by acting as a potential Bcl2 inhibitor in human glioma cells.


Designed post-self-assembly structural and functional modifications of a truncated tetrahedron.
Post-self-assembly modifications of a discrete metal-organic supramolecular structure have been developed. Such modifications allow the properties of the self-assembled supramolecular species to be changed in a simple and efficient manner (>90% yield). Initiated by the application of chemical stimuli, the post-self-assembly modifications described herein result in three distinct changes to the supramolecular system: an individual building-block component change, an overall structural modification, and a functional evolution of a [6+4] metal-organic supramolecular structure. The three modifications have been carefully examined by a range of characterization methods, including NMR and UV-vis spectroscopy, electrospray ionization mass spectrometry, pulsed field gradient spin echo NMR measurements, electrochemical analysis, and computational simulations.


Object-position binding in visual short-term memory for sequentially presented unfamiliar stimuli.
The effect of spatial position on visual short-term memory (VSTM) for sequentially presented objects has been investigated relatively little, despite the fact that vision in natural environments is characterised by frequent changes in object position and gaze location. We investigated the effect of reusing previously examined spatial positions on VSTM for object appearance. Observers performed a yes-no recognition task following a memory display comprising briefly presented 1/f noise discs (ie possessing spectral properties akin to natural images) shown sequentially at random coordinates. At test, single stimuli were presented either at original spatial positions, new positions, or at a fixed central position. Results, interpreted in terms of appearance and position preview effects, indicate that, where original spatial positions were reused at test, memory performance was elevated by more than 25%, despite that spatial position was task-irrelevant (in the sense that it could not be used to facilitate a correct response per se). This study generalises object-spatial-position binding theory to a sequential display scenario in which the influences of extrafoveal processing, spatial context cues, and long-term memory support were minimised, thereby eliminating the hypothesis that object priming is the principal cause of the 'same-position advantage' in VSTM.


Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin.
The mechanisms controlling the volume-regulated anion current (VRAC) are incompletely elucidated. Here, we investigate the modulation of VRAC by cellular cholesterol and the potential involvement of F-actin, Rho, Rho kinase, and phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P(2)] in this process. In Ehrlich-Lettre ascites (ELA) cells, a current with biophysical and pharmacological properties characteristic of VRAC was activated by hypotonic swelling. A 44% increase in cellular cholesterol content had no detectable effects on F-actin organization or VRAC activity. A 47% reduction in cellular cholesterol content increased cortical and stress fiber-associated F-actin content in swollen cells. Cholesterol depletion increased VRAC activation rate and maximal current after a modest (15%), but not after a severe (36%) reduction in extracellular osmolarity. The cholesterol depletion-induced increase in maximal VRAC current was prevented by F-actin disruption using latrunculin B (LB), while the current activation rate was unaffected by LB, but dependent on Rho kinase. Rho activity was decreased by approximately 20% in modestly, and approximately 50% in severely swollen cells. In modestly swollen cells, this reduction was prevented by cholesterol depletion, which also increased isotonic Rho activity. Thrombin, which stimulates Rho and causes actin polymerization, potentiated VRAC in modestly swollen cells. VRAC activity was unaffected by inclusion of a water-soluble PtdIns(4,5)P(2) analogue or a PtdIns(4,5)P(2)-blocking antibody in the pipette, or neomycin treatment to sequester PtdIns(4,5)P(2). It is suggested that in ELA cells, F-actin and Rho-Rho kinase modulate VRAC magnitude and activation rate, respectively, and that cholesterol depletion potentiates VRAC at least in part by preventing the hypotonicity-induced decrease in Rho activity and eliciting actin polymerization.


Molecular dynamics simulations of LysRS: an asymmetric state.
We report molecular dynamics simulations of the Escherichia coli Lysyl-tRNA synthetase LysU isoform carried out as a benchmark for mutant simulations in in silico protein engineering efforts. Unlike previous studies of aminoacyl-tRNA synthetases, LysU is modelled in its full dimeric form with explicit solvent. While developing a suitable simulation protocol, we observed an asymmetry that persists despite improvements to the model. This prediction has directly led to experiments that establish a functional asymmetry in nucleotide binding by LysU. The development of a simulation protocol and validation of the model are presented here. The observed asymmetry is described and the role of protein flexibility in developing the asymmetry is discussed.


Bias in treatment trials.
Rigorous treatment trials exhibit a number of key features to guard against bias. Randomization, blinding (of patients, care staff and assessors), full follow-up on all patients, and 'intention-to-treat' analyses all contribute to removing bias so that any true treatment effect can be revealed. This article outlines the rationale behind these features and advises how bias in treatment trials can be assessed.


The antibiotic susceptibility patterns of uropathogenic Escherichia coli, with special reference to the fluoroquinolones.
The emergence of drug resistance to trimethoprim-sulfamethoxazole, the penicillins, cephalosporins, and fluoroquinolones by Uropathogenic Escherichia coli (UPEC) has limited the options for selecting the appropriate antibiotic for the treatment of urinary tract infections. The The E. coli isolates, which were obtained from the culture of urine samples,were studied for their antibiotic resistance patterns, with special reference to the antimicrobial activity of the fluoroquinolones and the production of the extended spectrum β-lactamases. (ESBL), Settings and Design: This was a hospital based, prospective study which was done for a period of eighteen months. This study was done by using the standard culture techniques for urine samples, the modified Kirby-Bauer disk diffusion method for the antibiotic susceptibility testing and the disk diffusion method to confirm the ESBL production by the clinical isolates of E. coli in urine. The sensitivity pattern was correlated with the clinical condition and the presence of the risk factors. The statistical analysis which was used: The statistical analysis was done by using the proportions of sensitive, resistant and intermediates. Descriptive statistics like the total, mean and percentage were done by using the Statistical Package for the Social Sciences (SPSS), version 15.0. The hospital isolates showed high degrees of resistance to the penicillins, cephalosporins, nalidixic acid and the fluoroquinolones, with 59% of the isolates being ESBL producers. The incidence of the multidrug resistant strains of Escherichia coli has been steadily increasing over the past few years. The knowledge on the resistance pattern of the bacterial strains in a geographical area will help in guiding the appropriate and the judicious use of antibiotics. Also, the formulation of an appropriate hospital antibiotic policy will go a long way in controlling these infections.


Tumor-Infiltrating Lymphocytes and Associations With Pathological Complete Response and Event-Free Survival in HER2-Positive Early-Stage Breast Cancer Treated With Lapatinib and Trastuzumab: A Secondary Analysis of the NeoALTTO Trial.
The presence of tumor-infiltrating lymphocytes (TILs) is associated with improved outcomes in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer treated with adjuvant trastuzumab and chemotherapy. The prognostic associations in the neoadjuvant setting of other anti-HER2 agents and combinations are unknown. To determine associations between presence of TILs, pathological complete response (pCR), and event-free survival (EFS) end points in patients with early breast cancer treated with trastuzumab, lapatinib, or the combination. The NeoALTTO trial (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization) randomly assigned 455 women with HER2-positive early-stage breast cancer between January 5, 2008, and May 27, 2010, to 1 of 3 neoadjuvant treatment arms: trastuzumab, lapatinib, or the combination for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide after surgery. The primary end point used in this study was pCR in the breast and lymph nodes, with a secondary end point of EFS. We evaluated levels of percentage of TILs using hematoxylin-eosin-stained core biopsy sections taken at diagnosis (prior to treatment) in a prospectively defined retrospective analysis. Levels of TILs were examined for their associations with efficacy end points adjusted for prognostic clinicopathological factors including PIK3CA genotype. Of the 455 patients, 387 (85.1%) tumor samples were used for the present analysis. The median (interquartile range [IQR]) level of TILs was 12.5% (5.0%-30.0%), with levels lower in hormone receptor-positive (10.0% [5.0%-22.5%]) vs hormone receptor-negative (12.5% [3.0%-35.0%]) samples (P = .02). For the pCR end point, levels of TILs greater than 5% were associated with higher pCR rates independent of treatment group (adjusted odds ratio, 2.60 [95% CI, 1.26-5.39]; P = .01). With a median (IQR) follow-up time of 3.77 (3.50-4.22) years, every 1% increase in TILs was associated with a 3% decrease in the rate of an event (adjusted hazard ratio, 0.97 [95% CI, 0.95-0.99]; P = .002) across all treatment groups. The presence of TILs at diagnosis is an independent, positive, prognostic marker in HER2-positive early breast cancer treated with neoadjuvant anti-HER2 agents and chemotherapy for both pCR and EFS end points. clinicaltrials.gov Identifier: NCT00553358.


A Rare Case of Tracheal Crystal-Storing Histiocytosis Associated with Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue.
Crystal-storing histiocytosis (CSH) is a rare non-neoplastic histiocytic lesion with abnormal accumulation of immunoglobulin (Ig) light chain. CSH is associated with Ig overproduction by B-lymphoproliferative disorders (B-LPDs) or by persistent inflammatory diseases. Eighteen cases of pulmonary CSH have been reported. However, no case reports of tracheal CSH have been published. In this patient, we found a solitary tracheal tumor in an asymptomatic 60-year-old man on chest computed tomography scan. Histologically, the tumor comprised two different lesions. One lesion showed diffuse proliferation of spindle-shaped histiocytes with abundant eosinophilic granular cytoplasm. With immunohistochemistry, the histiocytic cells were positive for CD68, CD163 and Ig kappa light chain, and the cytoplasm was weakly positive for anaplastic lymphoma kinase (ALK) protein. Fluorescence in situ hybridization indicated no split signals for the ALK gene. Electron microscopy demonstrated many elongated or rhomboid-shaped dense crystals in the cytoplasm of histiocytes. The second lesion showed proliferation of CD20-positive small atypical lymphocytes mixed with Ig kappa chain-positive plasma cells. A diagnosis of CSH and concomitant mucosa-associated lymphoid tissue lymphoma was made. In this patient, unexpected ALK protein was detected in infiltrating histiocytes. Therefore, careful assessment of the ALK protein and gene was necessary to differentiate from other histiocytic disorders.


The Impact of Intraoperative Microvascular Compromise on Outcomes in Microsurgical Breast Reconstruction.
In microsurgical breast reconstruction, the nature and fate of postoperative vascular compromise has been well studied, but limited data exist on intraoperative vascular compromise. A review of all breast free flaps between 2007 and 2012 was performed. Details of intraoperative vascular compromise were recorded. Patients who experienced intraoperative microvascular compromise (Group I) were compared with patients who experienced only postoperative microvascular compromise (Group P) and all other patients (Group N). A total of 612 microsurgical breast reconstructions were reviewed. There were 73 (11.9%) flaps in Group I, 27 (4.4%) in Group P, and 512 (83.7%) in Group N. Compared with Group P, Group I more often involved arterial problems (p = 0.01), required supercharging for venous problems (p = 0.02), and was more likely to be salvaged (89.0 vs. 70.4%, p = 0.03). Group I had a similar overall complication rate compared with all other flaps (Group N + P) (31.5 vs. 27.1%, p = 0.49), but a higher flap loss rate (11.0 vs. 1.7%, p = 0.0003). The need to perform > 1 arterial revision was a risk factor for flap loss in Group I (p = 0.028). Total ischemia times > 175 minutes (p = 0.047) and reperfusion times > 80 minutes (p = 0.041) significantly increased the risk of flap loss to approximately 50%. Intraoperative vascular problems occur more frequently than postoperative vascular problems but are more frequently salvaged. They do not increase the likelihood of reoperation or total complications compared with all other flaps but do increase the risk of flap loss.


Genetic evidence that Notch affects independently the development of machrochaeta and wing venation in Drosophila melanogaster.
Temperature sensitive experiments on the interaction of Abruptex mutations of the Notch locus and Enhancer of split indicate that the effect of temperature on the development of macrochaeta and wing venation is different. This suggest that Notch affects the development of macrochaeta and wing venation in different and independent ways being in accordance with the proposition that the signal pathway from the Notch receptor at the cell membrane to Enhancer of split complex in the nucleus is different in the case of the development of macrochaeta and wing venation. The Abruptex mutations as gain-of-function mutations of the Notch locus cannot rescue the Enhancer of split phenotype.


The effect of different bypass flow rates and low-dose dopamine on gut mucosal perfusion and outcome in cardiac surgical patients.
The aim of this double-blind, randomized, placebo-controlled trial was to investigate the effects of different cardiopulmonary bypass flow rates and low-dose dopamine on gastric mucosal pH (pHi) and outcome. We hypothesized that by minimizing gut mucosal hypoperfusion during and after cardiac surgery endotoxin translocation may be prevented, resulting in an improved clinical outcome. Four groups of 25 patients each receiving high or low flows during bypass and low-dose dopamine or saline for 24 hours after induction of anaesthesia were studied. The pHi was measured at six time intervals over 24 hours. The combination of low-dose dopamine and a low bypass flow rate was associated with a significantly greater frequency and severity of low pHi. This group also demonstrated a significantly lower vascular resistance on admission to the intensive care unit. There may be an association between low pHi and low vascular resistance.


Phenotypic and genomic analysis of Zymomonas mobilis ZM4 mutants with enhanced ethanol tolerance.
Zymomonas mobilis ZM4 is an ethanol-producing microbe that is constitutively tolerant to this solvent. For a better understanding of the ethanol tolerance phenomenon we obtained and characterized two ZM4 mutants (ER79ap and ER79ag) with higher ethanol tolerance than the wild-type. Mutants were evaluated in different ethanol concentrations and this analysis showed that mutant ER79ap was more tolerant and had a better performance in terms of cell viability, than the wild-type strain and ER79ag mutant. Genotyping of the mutant strains showed that both carry non-synonymous mutations in clpP and spoT/relA genes. A third non-synonymous mutation was found only in strain ER79ap, in the clpB gene. Considering that ER79ap has the best tolerance to added ethanol, the mutant alleles of this strain were evaluated in ZM4 and here we show that while all of them contribute to ethanol tolerance, mutation within spoT/relA gene seems to be the most important.


HLA-DRB1 alleles genotyping in patients with rheumatoid arthritis in Chinese.
To explore the role of HLA-DRB1 genes in the development of rheumatoid arthritis (RA) and the correlations between HLA-DR alleles and clinical manifestations of patients with RA. 86 patients with rheumatoid arthritis and 106 race matched controls were studied in whom HLA-DR typing was performed by the method of DNA amplification with sequence-specific primers (PCR-SSP). The subtypes of HLA-DR4 were determined by the method of hybridization of PCR products with sequence-specific oligonucleotides (PCR-SSO). The absence or presence of HLA-DR4 and its subtypes was correlated with the clinical and serological characteristics of the patients. Compared with controls, an increased gene frequency of HLA-DR4 (48.8% vs 17.9%, P < 0.001) and a decreased frequency of HLA-DR7 (16.3% vs 27.4%, P = 0.06) were found. The DRB1* 0405 account for 61.9% of DR4+RA patients and 21.1% of DR4+ controls (P < 0.01). There was no difference between the DR4+ and DR4- patients with respect to age, sex, duration of disease, rheumatoid factor (RF), extra-articular manifestations including secondary Sjogren's syndrome. According to the wrist X-ray stage, the patients of DR4+ were more severe than that of DR4- (P < 0.05). HLA-DR4 and DR4 subtype of DRB1*0405 are related to the development of RA in Chinese. HLA-DR4 can be a useful prognostic marker in the patients with RA.


Is de novo membranous nephropathy suggestive of alloimmunity in renal transplantation? A case report.
Post-transplant nephrotic syndrome (PTNS) in a renal allograft carries a 48% to 77% risk of graft failure at 5 years if proteinuria persists. PTNS can be due to either recurrence of native renal disease or de novo glomerular disease. Its prognosis depends upon the underlying pathophysiology. We describe a case of post-transplant membranous nephropathy (MN) that developed 3 mo after kidney transplant. The patient was properly evaluated for pathophysiology, which helped in the management of the case. This 22-year-old patient had chronic pyelonephritis. He received a living donor kidney, and human leukocyte antigen-DR (HLA-DR) mismatching was zero. PTNS was discovered at the follow-up visit 3 mo after the transplant. Graft histopathology was suggestive of MN. In the past antibody-mediated rejection (ABMR) might have been misinterpreted as de novo MN due to the lack of technologies available to make an accurate diagnosis. Some researchers have observed that HLA-DR is present on podocytes causing an anti-DR antibody deposition and development of de novo MN. They also reported poor prognosis in their series. Here, we excluded the secondary causes of MN. Immunohistochemistry was suggestive of IgG1 deposits that favoured the diagnosis of de novo MN. The patient responded well to an increase in the dose of tacrolimus and angiotensin converting enzyme inhibitor. Exposure of hidden antigens on the podocytes in allografts may have led to subepithelial antibody deposition causing de novo MN.


The RNA/protein symmetry hypothesis: experimental support for reverse translation of primitive proteins.
Although the "RNA-world" theory, or the RNA-first theory is renowned for a promising theory of biogenesis, it is also possible that both RNAs and proteins have coevolved forming a stable metabolic complex from the very beginning. I investigated this possibility assuming that the genetic information flowed symmetrically in the era of the origin of life, i.e. the primitive translation machinery worked in both directions (from RNA to protein and from protein to RNA). According to this RNA/protein symmetry theory, the genetic information would have come from existing cellular proteins via reverse translation. This process would have been completed in a short period of time without searching an enormous RNA sequence space. Furthermore, reverse translation would have ensured biological continuity; proteins that were essential for cellular metabolism would have been utilized in the same way as before the protein sequence information would have been transferred into the RNA sequences. I also propose a possible mechanism for the process of reverse translation. The reverse translation would proceed in the 3' to 5' direction using a set of at least 20 reverse transfer RNAs (rtRNAs) that can recognize their specific amino acid residue and carry their corresponding codon. A source of genetic information would be a primary sequence of a protein molecule. Several basic steps of reverse translation were demonstrated using rtRNA(Arg).


Prediction of Prognostic Hemodynamic Indices in Pulmonary Hypertension Using Non-Invasive Parameters.
Effective targeted therapy of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) requires regular risk stratification. Among many prognostic parameters, three hemodynamic indices: right atrial pressure, cardiac index, and mixed venous saturation are considered critically important for correct risk classification. All of them are measured invasively and require right heart catheterization (RHC). The study was aimed to verify assumption that a model based on non-invasive parameters is able to predict hemodynamic profile described by the mentioned invasive indices. A group of 330 patients with pulmonary hypertension was used for the selection of the best predictors from the set of 17 functional, biochemical, and echocardiographic parameters. Multivariable logistic regression models for the prediction of low-risk and high-risk profiles were created. The cut-off points were determined and subsequent validation of the models was conducted prospectively on another group of 136 patients. The ROC curve analysis showed the very good discrimination power of the models (AUC 0.80-0.99) in the prediction of the hemodynamic profile in the total validation group and subgroups: PAH and CTEPH. The models indicated the risk profiles with moderate sensitivity (57-60%) and high specificity (87-93%). The method enables estimation of the hemodynamic indices when RHC cannot be performed.


Traffic-light system developed to prioritise cancer treatments.
Acute oncology services have been developed to meet the unplanned, urgent care needs of patients with cancer more effectively. Such patients often develop problems associated with the disease or the side effects of its treatment and present to emergency departments or medical assessment units, and their care must be timely if outcomes are to be positive. This article describes an education package that includes a traffic-light system to help emergency care staff prioritise the management of these patients and to meet their learning needs. The article also includes results of an evaluation of the programme and an account of how best to disseminate knowledge of cancer care in clinical settings.


Factors Associated With Health Care Utilization of Recurrent Clostridium difficile Infection in New York State.
The incidence of infection due to Clostridium difficile infection (CDI) and subsequent economic burden are substantial. The impact of changing practice patterns on demographics at risk and utilization of health care resources for recurrence of CDI remains unclear. A total of 291,163 patients hospitalized for CDI were identified from 1995 to 2014 from the New York SPARCS database. The χ test, the Welch t test, and multivariable logistic regression analysis were performed to evaluate factors related to readmission. Hospital admissions and readmissions for CDI peaked in 2008 at 20,487 and 13,795, respectively, and have since decreased (linear trend, 0.9706 and 0.9464, respectively; P<0.0001). In total, 60,077 (21%) patients required ≥2 admissions. Risk factors for readmission included: age 55 to 74, government insurance, hypertension, diabetes, anemia, hypothyroidism, chronic pulmonary disease, rheumatoid arthritis, renal failure, peripheral vascular disease, and depression (all P<0.05). Trends in surgery showed a similar peak in 2008 at 165 and have since decreased (linear trend, 0.8660; P<0.0001). A total of 1830 (0.63%) patients with CDI underwent surgery, with emergent being more common than elective (71% vs. 29%). Hospital admissions and readmissions for CDI peaked in 2008 and have since been steadily declining. These trends may be secondary to improved diagnostic capabilities and evolving antibiotic regimens. More than 1 in 5 hospitalized patients had at least 1 readmission. Numerous risk factors for these patients have been identified. Although <1% of all patients with CDI undergo surgery, these rates have also been declining.


Amino acid limitation regulates gene expression.
In mammals, the plasma concentration of amino acids is affected by nutritional or pathological conditions. For example, an alteration in the amino acid profile has been reported when there is a deficiency of any one or more of the essential amino acids, a dietary imbalance of amino acids, or an insufficient intake of protein. We examined the role of amino acid limitation in regulating mammalian gene expression. Depletion of arginine, cystine and all essential amino acids leads to induction of insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and protein expression in a dose-dependent manner. Moreover, exposure of HepG2 cells to amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed on a low-protein diet leads to a significantly higher (P < 0.0002) expression of IGFBP-1. Using CCAAT/enhancer-binding protein homologous protein (CHOP) induction by leucine deprivation as a model, we have characterized the molecular mechanisms involved in the regulation of gene expression by amino acids. We have shown that leucine limitation leads to induction of CHOP mRNA and protein. Elevated mRNA levels result from both an increase in the rate of CHOP transcription and an increase in mRNA stability. We have characterized two elements of the CHOP gene that are essential to the transcriptional activation produced by an amino acid limitation. These findings demonstrate that an amino acid limitation, as occurs during dietary protein deficiency, can induce gene expression. Thus, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.


Systems biology in the central nervous system: a brief perspective on essential recent advancements.
As recent advances in human genetics have begun to more rapidly identify the individual genes contributing to risk of psychiatric disease, the spotlight now turns to understanding how disruption of these genes alters the brain, and thus behavior. Compared to other tissues, cellular complexity in the brain provides both a substantial challenge and a significant opportunity for systems biology approaches. Current methods are maturing that will allow for finally defining the 'parts list' for the functioning mouse and human brains, enabling new approaches to defining how the system goes awry in disorders of the CNS. However, the availability of tissue is certainly a challenge for systems biology of neuroscience, compared to systems biology of other tissues, where biopsy is feasible. This challenge is particularly notable for disorders caused by extremely rare genetic variants. Thus computational and systems biology approaches, as well as precise experimental models by way of genome editing, will play key roles in defining mechanisms for disorders, and their individual symptoms, across varied genetic etiologies. Here, we highlight recent progress in neurogenetics, postmortem genomics, cell-type specific profiling, and precision modeling toward defining mechanisms in disease.


PEPCase Transcript Levels in Mesembryanthemum crystallinum Decline Rapidly upon Relief from Salt Stress.
Mesembryanthemum crystallinum plants respond to water stress by changing their pathway of carbon assimilation from C(3) to Crassulacean acid metabolism (CAM). Stressed plants are characterized by elevated levels of phosphoenolpyruvate carboxylase (PEPCase) mRNA, protein, and enzyme activity. We wanted to determine whether CAM is a reversible response to environmental conditions or a developmentally programmed adaptation that is irreversibly expressed once induced. Plants were osmotically stressed by irrigation with 500 millimolar NaCl for 12 days to elicit CAM. Salt was then thoroughly flushed from the soil and PEPCase protein and transcript levels were monitored. PEPCase mRNA levels dropped by 77% within 2.5 hours after salt removal. PEPCase activity and polypeptide levels declined more slowly, with a half-life of 2 to 3 days. These results show that PEPCase expression in M. crystallinum is a reversible response to stress that is regulated at the level of transcription or stability of the PEPCase mRNA.


The Nance-Horan syndrome: a rare X-linked ocular-dental trait with expression in heterozygous females.
This report describes two families with the Nance-Horan syndrome, an X-linked trait featuring lenticular cataracts and anomalies of tooth shape and number. Previous reports have described blindness in affected males but posterior sutural cataracts with normal vision as the primary ocular expression in heterozygous females. In one of these two families, the affected female is not only blind in one eye but reportedly had supernumerary central incisors (mesiodens) removed. This constitutes the most severe ocular and dental expression of this gene in heterozygous females yet reported.


Disease course of patients with unilateral pigmentary retinopathy.
To evaluate the change in ocular function by eye in patients with unilateral pigmentary retinopathy. Longitudinal regression was used to estimate mean exponential rates of change in Goldmann visual field area (V4e white test light) and in full-field electroretinogram (ERG) amplitudes to 0.5- and 30-Hz white flashes in 15 patients with unilateral pigmentary retinopathy. Snellen visual acuity was assessed case by case. Mean annual rates of change for the affected eyes were -4.9% for visual field area, -4.7% for ERG amplitude to 0.5-Hz flashes, and -4.6% for ERG amplitude to 30-Hz flashes. All three rates were faster than the corresponding age-related rates of change for the fellow normal eyes (P = 0.0006, P = 0.003, P = 0.03, respectively). An initial cone ERG implicit time to 30-Hz flashes in affected eyes ≥ 40 ms predicted a faster mean rate of decline of visual field area and of ERG amplitude to 0.5- and 30-Hz flashes (P < 0.0001 for all three measures). The visual acuity of affected eyes was more likely to decrease in patients presenting at >35 years of age than in patients presenting at a younger age (P = 0.0004). The affected eye in unilateral pigmentary retinopathy shows a progressive loss of peripheral retinal function that cannot be attributed to aging alone and that is faster in eyes with a more prolonged initial cone ERG implicit time. Patients presenting at >35 years of age are at greater risk for losing visual acuity.


Identification and Function Analysis of a Five-Long Noncoding RNA Prognostic Signature for Endometrial Cancer Patients.
This study aimed to construct a long noncoding RNA (lncRNA)-based prognostic signature to improve the survival prediction for endometrial cancer (EC) patients and guide individualized treatments. mRNA and miRNA sequencing and clinical data of 526 patients with EC (randomized to training or validation set, n = 263) were collected from The Cancer Genome Atlas database. Differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs), and differentially expressed miRNAs (DEMs) were identified between 263 EC samples and 33 normal controls. Univariate and multivariate Cox regression analyses identified five DELs (LINC00475, LINC01352, MIR503HG, KCNMB2-AS1, and LINC01143) that were overall survival related. The Kaplan-Meier curve showed that the risk score model established by these five DELs can significantly distinguish the survival ratio of patients at high risk from those at low risk. The receiver operating characteristic curve indicated that this risk score exhibited good survival prediction performance, with the area under the curve of 0.978. In addition, this risk score was independent of other clinical factors. Stratification analysis based on two independent prognostic clinical factors (histologic grade and recurrence status) demonstrated that the high-risk score was still a poor prognostic factor for patients with histologic grade 3, recurrence or nonrecurrence status. In nomogram model, the risk score was one of the main contributions to survival rates, and its Harrell's concordance index was higher than the other two independent clinical factors, although all lower than the combined. Furthermore, mechanism analyses showed that these lncRNAs functioned by coexpressing with DEGs (i.e., LINC00475-PTGDR, LINC01352/MIR503HG-BACH2, KCNMB2-AS1-PCSK9, LINC01143-NUF2/PTTG1) or as a competing endogenous RNA of DEMs to regulate DEGs (LINC00475-miR-4728-PTGDR, MIR503HG-miR-3170-BACH2). In conclusion, our novel risk score system may be a promising prognostic biomarker to guide personalized treatment for EC patients and it can add prognostic value for current clinical system.


Personality profile in young current regular users of cocaine.
This study examined the relationship between the personality profile of a sample of cocaine users and the presence of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnoses and the severity of substance use. A total of 120 participants (46 women, mean age: 23.8 years) from nonclinical settings in Barcelona, Spain, 2003-2006, were assessed using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) and the Temperament and Character Inventory-Revised version (TCI-R). Most of the participants had completed more than primary education, nearly half of them were employed, one third lived with parents, and near a quarter had some criminal record. Snorting was the main route of cocaine administration. They were using a mean of 1.82 substances. Cocaine users with low Self-Directedness, low Cooperativeness, and high Self-Transcendence scores in the TCI-R, with high severity of substance use and psychiatric comorbidity, would be suggestive of a possible specific phenotype. The limitations and implications of the study are discussed.


Successfully implementing a multihospital cost system.
Addressing the problems of developing a cost accounting system for a multihospital system is never an easy task. Basically, these systems need to have cost data easily accessible to all managers of all institutions in the healthcare system. The need for accurate, cost-effective, and controlled data is necessary to maintain the competitive edge required for organizational success.


Short Sleep Duration on the Night Before Surgery Is Associated With Postoperative Cognitive Decline in Elderly Patients: A Prospective Cohort Study.
As the world is rapidly aging, and the number of elderly patients who undergo surgery is rising, postoperative cognitive decline among those patients has become an increasing healthcare problem. Although understanding the risk factors and mechanisms underlying the pathogenesis of postoperative cognitive decline is critically important from a preventative viewpoint, such knowledge and evidence are lacking. A growing body of evidence suggest an association between cognitive function and sleep duration. The purpose of this study was to investigate the association between postoperative cognitive function and sleep duration on the night before surgery using a wearable sleep tracker. In this 6-month prospective cohort study, we analyzed data from 194 patients aged ≥ 65 years who underwent elective non-cardiac and non-cranial surgery under general anesthesia. According to the sleep duration on the night before surgery, patients were categorized into following four groups: <5, 5-7, 7-9, and >9 h. Perioperative cognitive function and domains were assessed using a neuropsychological test battery, and the incidence and prevalence of cognitive decline over 6 months after surgery were analyzed using the multiple logistic regression analysis. During the 6-month follow-up period, 41 patients (21%) developed cognitive decline. The incidence of cognitive decline was significantly elevated for the patients with sleep duration < 5 h (vs. 7-9 h; surgical duration-adjusted odds ratio, 3.50; 95% confidence interval, 1.20-10.2; P < 0.05). The association between sleep duration and prevalence of cognitive decline was limited to the early postoperative period (at 1 week and 1 month). Among the cognitive domains assessed, attentional function was significantly impaired in patients with a sleep duration < 5 h [vs. 7-9 h at 1 week; 4/37 (10.8%) vs. 0/73 (0%); P < 0.05]. In conclusion, sleep duration < 5 h on the night before surgery was significantly associated with worse attentional function after surgery and higher incidence of cognitive decline. The present results indicate that sleep deprivation on the night before surgery may have a temporary but significantly negative influence on the patient's postoperative cognitive function and is a potential target for preventing cognitive decline.


Cheyne-stokes ventilation converting to obstructive sleep apnea following heart transplantation.
Cheyne-Stokes ventilation is often found in conjunction with heart failure. The pathogenesis is multifactorial and upper airway instability has been suggested to play a role. This report documents the conversion of Cheyne-Stokes ventilation during sleep to obstructive apnea after heart transplantation.


[HIV Test in Pregnancy - 100% Not Reached in 2020].
In 2019 38 million people were living with HIV worldwide, more than half of them girls and women. Knowledge about maternal HIV status enables HIV transmission prophylaxis, reducing mother-to-child transmission<1%. We aimed to investigate the implementation of the mandatory documentation of counseling and optional HIV testing in the maternity records as recommended in the German maternity guidelines. In the Obstetric Department of the University Hospital Bonn, maternity records were reviewed from June to October 2020, and pregnant women were interviewed regarding the patients' recall of counseling and HIV testing as well as their attitude towards a universal screening strategy using an anonymous questionnaire. Documentation was incomplete in 11% of maternal records: in 8% there was neither documentation of counseling nor of HIV testing, in 3% documentation of counseling only. In 291 questionnaires 47% of pregnant women could not recall counselling. 90% of pregnant women were in favor of universal HIV testing in pregnancy, 9% were undecided, and 1% opposed it. 55% would support change from an "opt-in" to an "opt-out" screening policy in pregnancy. Documentation of counseling and HIV testing was incomplete in 11% of cases, and nearly half of the women could not recall counselling. New strategies from midwives and obstetricians need to be developed to achieve universal HIV testing in pregnant women leading to zero HIV mother-to-child transmissions.


Combined Aortic and Mitral Valve Stenosis in Mucopolysaccharidosis Syndrome Type I-S: A Report of a Rare Case.
Mucopolysaccharidosis (MPS) syndrome is an inherited metabolic disorder. In more than half of the patients with MPS syndrome, heart valve involvement is reported; however, combined aortic and mitral valve stenosis in MPS syndrome type I-S is very rare. We describe a 39-year-old man with severe mitral and aortic valve stenosis due to MPS syndrome type I-S. Transthoracic and transesophageal echocardiography revealed severe thickening and calcification in the aortic and mitral valves with severe left ventricular hypertrophy. The coronary arteries were normal in angiography.


Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory Neurons.
Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked (eas), which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE) synthesis, and two other enzymes in this synthesis pathway are required cell autonomously in sensory neurons for dendrite growth and stability. Furthermore, we show that the level of Sterol Regulatory Element-Binding Protein (SREBP) activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis.


Thermoelectric Properties of Hexagonal M₂C₃ (M = As, Sb, and Bi) Monolayers from First-Principles Calculations.
Hexagonal M₂C₃ compound is a new predicted functional material with desirable band gaps, a large optical absorption coefficient, and ultrahigh carrier mobility, implying its potential applications in photoelectricity and thermoelectric (TE) devices. Based on density-functional theory and Boltzmann transport equation, we systematically research the TE properties of M₂C₃. Results indicate that the Bi₂C₃ possesses low phonon group velocity (~2.07 km/s), low optical modes (~2.12 THz), large Grüneisen parameters (~4.46), and short phonon relaxation time. Based on these intrinsic properties, heat transport ability will be immensely restrained and therefore lead to a low thermal conductivity (~4.31 W/mK) for the Bi₂C₃ at 300 K. A twofold degeneracy is observed at conduction bands along Γ-M direction, which gives a high n-type electrical conductivity. Its low thermal conductivity and high Seebeck coefficient lead to an excellent TE response. The maximum thermoelectric figure of merit (ZT) of n-type can approach 1.41 for Bi₂C₃. This work shows a perspective for applications of TE and stimulate further experimental synthesis.


[Sublingual hyposensitization].
Specific hyposensitization remains the only way to alter profoundly the progress of the allergic disease. The last discoveries in immunology allow better to understand the mechanisms of action. Now, we can use more purified and standardised solutions to improve the results. Subcutaneous way remains the gold method. But, since 10 years, European screws publishes the results of their works about alternative ways like sublingual way. Less dangerous and less compelling, it allows to begin the treatment earlier in the live and to give more important doses. The results are equivalent to the subcutaneous method. Recently, W.H.O. decided to consider sublingual immunotherapy as un full treatment of some allergic diseases.


FTO demethylates m6A modifications in HOXB13 mRNA and promotes endometrial cancer metastasis by activating the WNT signalling pathway.
Although many studies have confirmed the relationship between obesity and endometrial cancer (EC), the molecular mechanism between obesity and EC progression has not been elucidated. Overexpression of fat mass and the obesity associated protein FTO leads to weight gain, although recently it has been discovered that FTO can serve as a demethylase which erases N6-methyladenosine (m6A) modification and regulates the metabolization of mRNAs. In this study, we found high expression of FTO in metastatic EC and that this action promote both metastasis and invasion in vivo and in vitro. Mechanistically, FTO can catalyse demethylation modification in 3'UTR region of HOXB13 mRNA, thereby abolishing m6A modification recognition with the YTHDF2 protein. Decreasing HOXB13 mRNA decay and increasing HOXB13 protein expression was accompanied by WNT signalling pathway activation and the expression of downstream proteins, leading to tumour metastasis and invasion. We also found the WNT signalling pathway inhibitor ICG-001 can block HOXB13 gene-induced tumour metastasis, therefore ICG-001 may be a promising molecular intervention. This study provides insight into the relationship between obesity and the pathogenesis of endometrial cancer while highlighting future areas of research.


Neuromuscular electrical stimulation after anterior cruciate ligament surgery.
This randomized, double blind, controlled trial was designed to determine the effectiveness of neuromuscular electrical stimulation of the knee extensor and flexor muscles in the prevention of muscular weakening after anterior cruciate ligament surgery. Neuromuscular electrical stimulation treatment was given in addition to an early exercise therapy regimen and compared with an early exercise therapy regimen alone. Forty-nine patients after anterior cruciate ligament surgery were assigned randomly either to a neuromuscular electrical stimulation and exercise group, a transcutaneous electrical nerve stimulation as analgesic and exercise group, or an exercise alone group as control. All groups received a standard regimen of rehabilitation after anterior cruciate ligament surgery. The neuromuscular electrical stimulation and transcutaneous electrical nerve stimulation group additionally received electrical stimulation during the first 6 weeks after surgery. Patients were measured for isometric and isokinetic torque in the knee extensor and flexor muscles after 6, 12, and 52 weeks. No statistical difference among groups was observed. It is concluded that neuromuscular electrical stimulation in combination with an early exercise therapy regimen is not significantly more effective in reducing weakening than an early exercise therapy regimen alone after anterior cruciate ligament surgery.


Feasibility and Acute Safety Study of Radiofrequency Energy Delivery to the Vena Caval Wall via an IVC Filter in Swine.
Retrievable inferior vena cava (IVC) filters are self-expanding metallic devices implanted in the IVC to prevent migration of thrombi from the deep veins of the legs and pelvis to the lungs. The risk of complications from the filters increases with duration of implantation, but retrieval may be difficult due to intimal hyperplasia around the components of the filter. In this study, the potential for delivery of radiofrequency (RF) energy to the IVC wall via the filter was investigated. IVC filters were deployed in 4 swine while attached to a snare connected to a 480 kHz RF generator. Energy ranging from 0 to 48 kJ was applied via the filter followed by re-sheathing and withdrawal of the filter while connected to a force measurement device. Resheathing forces for the 0-energy cohort and pooled data from the 6-24 kJ cohorts were 4.50±0.70 N and 4.50±0.75 N, respectively. Petechial hemorrhages and variable non-occlusive thrombi were noted in some cohorts including the 0-energy cohort, consistent with delivery and acute retrieval of an IVC filter. Histologically, the extent of RF-induced injury was subtle at 6 kJ with focal areas of homogenized collagen while the 12 kJ cohort showed segmental tissue charring with coagulation necrosis which was more extensive for the 24 kJ cohort. The 48 kJ energy caused more extensive and non-target organ damage. The study demonstrated feasibility of delivery of RF to the IVC wall via a deployed filter, supporting further study of the ability of local RF heating of the IVC wall to inhibit the neointimal hyperplasia or as an aid in retrieval.


'We are essential:' Pediatric health care social workers' perspectives on being designated essential workers during the COVID-19 pandemic.
Continued provision of essential services is critical to maintaining society's functioning during a crisis. During COVID-19, lockdowns and restrictions designed to preserve the public's health forced an examination of what it means to be an essential worker. Drawing from thematic analyses of focus group data from 55 social workers employed in a large, urban, pediatric, quaternary hospital, this study examines the perspectives of hospital social workers on the meaning of the essential status designation of social work. Findings revealed themes pertaining the substance of social work, the ways in which essential status is carried out, and implications of the designation not only for the future of the profession but also for the populations who receive social work services. The discussion raised important questions about the essential role of social workers in broader health care settings. Our findings suggest that health care systems need to engage in ongoing discussions of how to maximize the efficacy of the social work workforce, both in terms of integration with medical teams and recognition of the important roles social workers play across the hospital system, and facilitate the performance of their essential functions.


Expert panel consensus recommendations for the pharmacological treatment of acute pain in the Middle East region.
The findings of an expert panel convened to review critically how best to apply evidence-based guidelines for the treatment of acute pain in the Middle East region are presented. The panel recommended a three-step treatment protocol. Patients with mild-to-moderate levels of acute pain should be treated with paracetamol (step 1). If analgesia is insufficient after 1-2 days, a selective cyclo-oxygenase-2 inhibitor or, if gastrointestinal safety and bleeding risk are not an issue, a non-specific nonsteroidal anti-inflammatory drug, should be used (step 2). If analgesia remains inadequate, treatment with tramadol, or paracetamol plus codeine/tramadol is recommended (step 3). Patients reporting severe pain should be referred to a pain clinic or specialist for opioid analgesic treatment. Measures of pain and functioning that have been validated in Arabic, with culturally appropriate and easy to understand descriptors, should be used. Early and aggressive acute pain management is important to reduce the risk of pain becoming chronic, especially in the presence of neuropathic features.


Liquid chromatography with tandem mass spectrometry method for the simultaneous determination of multiple sweet mogrosides in the fruits of Siraitia grosvenorii and its marketed sweeteners.
A high-performance liquid chromatography with electrospray ionization tandem mass spectrometry method has been developed and validated for the simultaneous quantification of eight major sweet mogrosides in different batches of the fruits of Siraitia grosvenorii and its marketed sweeteners. The sample preparation procedure and chromatographic and mass spectrographic conditions were optimized. Chromatographic separation was achieved on a reversed-phase Poroshell 120 SB C18 column in 10.0 min with gradient elution with acetonitrile and water, both of which contained 0.1% formic acid. The multiple reaction monitoring scanning mode was employed for quantification in the negative ion mode. The developed method was validated with acceptable linearity (r2 = 0.9984-0.9998) over a wide concentration range, precision (relative standard deviations = 1.09-3.91%), stability (relative standard deviations = 1.21-3.01%), and recovery in the range of 91.22-106.58% (relative standard deviations ≤ 3.79%) under optimum conditions. The proposed method was demonstrated to be simple, rapid, specific, and reliable and was successfully applied for the quality control of the fruits of S. grosvenorii and its marketed sweeteners.


Regio- and stereoselective ring openings of 3-Aza-2-oxabicyclo[2.2.1]hept-5-ene systems with copper catalyst-modified grignard reagents: application to the synthesis of an inhibitor of 5-lipoxygenase.
Treatment of acylnitroso hetero Diels-Alder cycloadducts 2 with organomagnesium reagents in the presence of a catalytic amount of copper induces ring opening to afford predominantly monocyclic anti-1,2-hydroxamic acids 12. Alkylmagnesium reagents were found to give superior regio- and stereoselectivities compared with vinyl and arylmagnesium reagents. This cycloadduct ring opening methodology was applied to the synthesis of a unique cyclopentenyl hydroxamic acid-based inhibitor of 5-lipoxygenase.


Structure of human Vitronectin C-terminal domain and interaction with Yersinia pestis outer membrane protein Ail.
Vitronectin (Vn) is a major component of blood that controls many processes central to human biology. It is a drug target and a key factor in cell and tissue engineering applications, but despite long-standing efforts, little is known about the molecular basis for its functions. Here, we define the domain organization of Vn, report the crystal structure of its carboxyl-terminal domain, and show that it harbors the binding site for the Yersinia pestis outer membrane protein Ail, which recruits Vn to the bacterial cell surface to evade human host defenses. Vn forms a single four-bladed β/α-propeller that serves as a hub for multiple functions. The structure explains key features of native Vn and provides a blueprint for understanding and targeting this essential human protein.


Radiation dose at cardiac computed tomography: facts and fiction.
Cardiac computed tomography (CT) dosimetry makes use of two radiation parameters: a volume CT dose index (CTDI) and a dose length product (DLP). The volume CTDI quantifies the intensity of the radiation used to perform CT examinations, whereas DLP quantifies the amount of radiation used. CTDI metrics can be converted into patient dose metrics by using dose/CTDI conversion factors. In cardiac CT imaging, these need to take into account the x-ray tube voltage, scan length, and scan region, as well as patient size. Organ doses to patients in cardiac CT can be converted into cancer risks when patient demographic factors are taken into account. A risk analysis of patients undergoing cardiac CT angiography at our institution showed that a majority (62%) were males, with a median age of approximately 60 years and a median weight of approximately 90 kg. The median DLP was approximately 1100 mGy cm, corresponding to an effective dose of approximately 29 mSv in normal-sized patients. The average patient lifetime risk for a radiation-induced cancer was estimated to be 0.12%, with 85% of it attributed to lung cancer. Patients with an age and weight at the 10th percentile, who also received a DLP at the 90th percentile, would have cancer risk estimates approximately double the average value. Radiation risks are required to determine whether examinations are indicated, defined as examinations in which individual patient benefit exceeds corresponding patient risk. Understanding radiation risks in cardiac CT encourages operators to use the least amount of radiation to achieve satisfactory diagnostic performance.


Control and Prevention of SARS-CoV-2 Outbreaks among Healthcare Workers from 129 Healthcare Facilities in Mexico.
Few reports have shared the workflows to reduce SARS-CoV-2 infections among risk groups, including healthcare workers (HCWs). This study describes an occupational health program implemented to reduce the incidence of COVID-19 and establishes a back-to-work algorithm in HCWs of 129 Salud Digna outpatient care clinics in Mexico. This program was composed of training plans, screening SARS-CoV-2 infections, the containment of infections, follow-up COVID-19 cases, and continuing supervision in addition to the steady supply and training for the correct use of PPE. From 16 April 2020 to 15 April 2021, 7376 individuals were enrolled, of which 423 were excluded because they did not meet the inclusion criteria or refused the follow-up. In the cohort studied, we found a COVID-19 incidence of 35.4% (2610 individuals), lower hospitalization (0.11%), ICU (0.04%) and lethality rate (0.04%). Additionally, 85.9% of COVID-19 cases tested negative for SARS-CoV-2 after 14 days of the first positive test with an average isolation time of 26-33 days. Finally, 99% of people received personal protective equipment and adequate training to use it. Our results show that the program implemented reduced the hospitalization ICU admission and lethality in HCWs; we consider this workflow to help other workplaces offer safe conditions for HCWs and patients.