Between-session reliability of opto-electronic motion capture in measuring sagittal posture and 3-D ranges of motion of the thoracolumbar spine.
This study evaluated between-session reliability of opto-electronic motion capture to measure trunk posture and three-dimensional ranges of motion (ROM). Nineteen healthy participants aged 24-74 years underwent spine curvature, pelvic tilt and trunk ROM measurements on two separate occasions. Rigid four-marker clusters were attached to the skin overlying seven spinous processes, plus single markers on pelvis landmarks. Rigid body rotations of spine marker clusters were calculated to determine neutral posture and ROM in flexion, extension, total lateral bending (left-right) and total axial rotation (left-right). Segmental spine ROM values were in line with previous reports using opto-electronic motion capture. Intraclass correlation coefficients (ICC) and standard error of measurement (SEM) were calculated as measures of between-session reliability and measurement error, respectively. Retroreflective markers showed fair to excellent between-session reliability to measure thoracic kyphosis, lumbar lordosis, and pelvic tilt (ICC = 0.82, 0.63, and 0.54, respectively). Thoracic and lumbar segments showed highest reliabilities in total axial rotation (ICC = 0.78) and flexion-extension (ICC = 0.77-0.79) ROM, respectively. Pelvic segment showed highest ICC values in flexion (ICC = 0.78) and total axial rotation (ICC = 0.81) trials. Furthermore, it was estimated that four or fewer repeated trials would provide good reliability for key ROM outcomes, including lumbar flexion, thoracic and lumbar lateral bending, and thoracic axial rotation. This demonstration of reliability is a necessary precursor to quantifying spine kinematics in clinical studies, including assessing changes due to clinical treatment or disease progression.


Genotoxicity of ethyl carbamate in the Drosophila wing spot test: dependence on genotype-controlled metabolic capacity.
Ethylcarbamate has a clear genotoxic potential in Drosophila melanogaster. In the somatic mutation and recombination test (SMART) it induces, in a dose-dependent manner, single spots as well as twin spots. The twin spots indicate a recombinogenic activity of ethyl carbamate. A strong strain difference demonstrates that the metabolic activation of ethyl carbamate to DNA binding metabolites most probably also in Drosophila involves cytochrome P450-dependent enzyme activities.


Reciprocal paracrine interactions between normal human epithelial and mesenchymal cells protect cellular DNA from radiation-induced damage.
To explore whether interactions between normal epithelial and mesenchymal cells can modulate the extent of radiation-induced DNA damage in one or both types of cells. Human primary thyrocytes (PT), diploid fibroblasts BJ, MRC-5, and WI-38, normal human mammary epithelial cells (HMEC), and endothelial human umbilical cord vein endothelial cells (HUV-EC-C), cultured either individually or in co-cultures or after conditioned medium transfer, were irradiated with 0.25 to 5 Gy of gamma-rays and assayed for the extent of DNA damage. The number of gamma-H2AX foci in co-cultures of PT and BJ fibroblasts was approximately 25% lower than in individual cultures at 1 Gy in both types of cells. Reciprocal conditioned medium transfer to individual cultures before irradiation resulted in approximately a 35% reduction of the number gamma-H2AX foci at 1 Gy in both types of cells, demonstrating the role of paracrine soluble factors. The DNA-protected state of cells was achieved within 15 min after conditioned medium transfer; it was reproducible and reciprocal in several lines of epithelial cells and fibroblasts, fibroblasts, and endothelial cells but not in epithelial and endothelial cells. Unlike normal cells, human epithelial cancer cells failed to establish DNA-protected states in fibroblasts and vice versa. The results imply the existence of a network of reciprocal interactions between normal epithelial and some types of mesenchymal cells mediated by soluble factors that act in a paracrine manner to protect DNA from genotoxic stress.


Seasonal changes in the migratory behaviour of the toad Bufo bufo: direction and magnitude of movements.
The migratory behaviour of the toad Bufo bufo was studied from February 1985 to April 1986 in the submontane region of Bavaria, West Germany. Toads were fitted with a mechanical tracking device to record individual paths of migration. Three aspects of migratory behaviour were quantified: orientation in relation to the breeding site, straightness of path, and locomotory activity. The annual activity period began with migration from the hibernation sites to the breeding pond in April. The paths went straight towards the breeding pond independent of the distance (70-420 m). During the period of oviposition the preference for the breeding site direction vanished and toads moved away from the breeding pond, but in less straight paths than before. In summer migratory activity decreased considerably and was restricted to small areas, the home ranges, at distances of 55-1600 m from the natal breeding pond. The straightness of path was rather low, because toads often returned to their starting points. During rainy nights toads occasionally left their home ranges for extensive excursions. In autumn most toads again migrated towards the breeding pond, but paths were significantly less straight and direct than in spring. However, toads stopped before reaching the breeding pond and hibernated in holes or under the leaf layer. The mortality rate of tracked toads was about 45%. The relative influence of 17 environmental variables on locomotory activity was evaluated by principal component analysis and stepwise multiple regression. Temperature at night and rainfall variables accounted for significant amounts of variance, whereas temperature by day, air humidity, and atmospheric pressure showed no correlation. Activity decreased if temperature approached 0° C or after long periods without rainfall. Within a certain range of tolerance, however, the locomotory activity of the toads was widely independent of environmental factors, indicating that endogeneous factors are more important sources of variation in the migratory behaviour of these toads than commonly assumed.


Evaluation of the MC-Media Pad® Rapid Aerobic Count Device for the Enumeration of Total Aerobic Counts in a Variety of Foods: Collaborative Study, First Action Official MethodSM 2019.02.
The MC-Media Pad® Rapid Aerobic Count (RAC) is a ready-to-use culture device combining a test pad coated with medium and water absorption polymers that are designed for the rapid quantification of total aerobic bacteria in food products. The MC-Media Pad RAC was compared to the U.S. Department of Agriculture Food Safety and Inspection Service Microbiology Laboratory Guidebook, Chapter 3.02: Quantitative Analysis of Bacteria in Foods as Sanitary Indicators for raw ground pork and the Standard Methods for the Examination of Dairy Products, Chapter 6: Microbial Count Methods for yogurt drink. The candidate method was evaluated against the reference methods using a paired study design in a multi-collaborator study, following the current AOAC INTERNATIONAL Official Methods of AnalysisSM Appendix J guidelines. Three target contamination levels (low, medium, and high) were evaluated. MC-Media Pad RAC devices were enumerated after 24 and 48 h of incubation. Plate counts obtained by both methods were log10-transformed and the difference of means (including 95% confidence intervals), repeatability SD, and reproducibility SD were determined for each contamination level. All 95% confidence intervals for mean difference fell easily within ±0.10, the performance requirement being ±0.5. The MC-Media Pad RAC (for both 24 and 48 h) and both reference methods for each contamination level were therefore shown to be equivalent, with 97.5% confidence. The new method offers a convenient alternative to the reference methods for detection of aerobic plate count in food products, yielding reliable and comparable results in 24 or 48 h compared to 48 h for the reference methods.


An enzyme-coupled microplate assay for activity and inhibition of hmdUMP hydrolysis by DNPH1.
2'-Deoxynucleoside 5'-monophosphate N-glycosidase 1 (DNPH1) hydrolyzes the epigenetically modified nucleotide 5-hydroxymethyl 2'-deoxyuridine 5'-monophosphate (hmdUMP) derived from DNA metabolism. Published assays of DNPH1 activity are low throughput, use high concentrations of DNPH1, and have not incorporated or characterized reactivity with the natural substrate. We describe the enzymatic synthesis of hmdUMP from commercially available materials and define its steady-state kinetics with DNPH1 using a sensitive, two-pathway enzyme coupled assay. This continuous absorbance-based assay works in 96-well plate format using nearly 500-fold less DNPH1 than previous methods. With a Z prime value of 0.92, the assay is suitable for high-throughput assays, screening of DNPH1 inhibitors, or characterization of other deoxynucleotide monophosphate hydrolases.


The physiological effect of organophosphate flame retardants (OPFRs) on wheat (Triticum aestivum L.) seed germination and seedling growth under the presence of copper.
This study investigated the physiological and biochemical impacts of organophosphate flame retardants (OPFRs) on wheat (Triticum aestivum L.) germination and growth performance in the presence and absence of copper. The study evaluated seed germination, growth, OPFRs concentrations, chlorophyll fluorescence index (Fv/Fm and Fv/F0), and antioxidant enzyme activity. It also calculated the root accumulation of OPFRs and their root-stem translocation. At the germination stage, at a concentration of 20 μg·L-1 OPFR exposure, wheat germination vigor, root, and shoot lengths were significantly decreased compared to the control. However, the addition of a high concentration of copper (60 mg·L-1) decreased by 80%, 82%, and 87% in the seed germination vitality index and root and shoot elongation, respectively, compared to 20 μg·L-1 of OPFR treatment. At the seedling stage, a concentration of 50 μg·L-1 of OPFRs significantly decreased by 42% and 5.4% in wheat growth weight and the photochemical efficiency of photosystem II (Fv/Fm) compared to the control. However, the addition of a low concentration of copper (15 mg·L-1) slightly enhanced the growth weight compared to the other two co-exposure treatments, but the results were not significant (p > 0.05). After 7 days of exposure, the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) (indicates lipid peroxidation) content in wheat roots significantly increased compared to the control and was higher than in leaves. MDA contents in wheat roots and shoots were decreased by 18% and 6.5% when OPFRs were combined with low Cu treatment compared with single OPFRs treatment, but SOD activity was slightly improved. These results suggest that the co-exposure of copper and OPFRs enhances reactive oxygen species (ROS) production and oxidative stress tolerance. Seven OPFRs were detected in wheat roots and stems, with root concentration factors (RCFs) and translocation factors (TFs) ranging from 67 to 337 and 0.05 to 0.33, respectively, for the seven OPFRs in a single OPFR treatment. The addition of copper significantly increased OPFR accumulation in the root and aerial parts. In general, the addition of a low concentration of copper promoted wheat seedling elongation and biomass and did not significantly inhibit the germination process. OPFRs could mitigate the toxicity of low-concentration copper on wheat but had a weak detoxification effect on high-concentration copper. These results indicated that the combined toxicity of OPFRs and Cu had antagonistic effects on the early development and growth of wheat.


Reassortment of Influenza A Viruses in Wild Birds in Alaska before H5 Clade 18.104.22.168 Outbreaks.
Sampling of mallards in Alaska during September 2014-April 2015 identified low pathogenic avian influenza A virus (subtypes H5N2 and H1N1) that shared ancestry with highly pathogenic reassortant H5N2 and H5N1 viruses. Molecular dating indicated reassortment soon after interhemispheric movement of H5N8 clade 220.127.116.11, suggesting genetic exchange in Alaska or surrounds before outbreaks.


Cloning and expression of human aldose reductase.
The complete amino acid sequence of human retina and muscle aldose reductase was determined by nucleotide analysis of cDNA clones isolated using synthetic oligonucleotide probes based on partial amino acid sequences of purified human psoas muscle aldose reductase. The cDNA sequence differs substantially in the noncoding and coding regions of recently published sequences of this enzyme. The mRNA for aldose reductase was abundantly expressed in HeLa cells, but only scarcely in a neuroblastoma cell line. Recombinant baculovirus containing one of the muscle cDNA clones was constructed and used to infect Spodoptera frugiperda (SF9) cells. A prominent protein with an apparent molecular size of 36 kDa was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the culture medium as well as in the homogenate of SF9 cells after 2 days of infection. Culture medium or the supernatant fraction of cell homogenates containing this protein had high aldose reductase activity which showed characteristics of the reported human enzyme. These findings indicate that the amino acid sequence reported in this paper represents human retina and muscle aldose reductase and that functional human aldose reductase can be expressed in large amounts in a baculovirus expression system. The result should facilitate refined structural analysis and the development of new specific aldose reductase inhibitors for the treatment of diabetic complications.


A novel alginate localization molding technique for cross-sectional area measurement of human tendon to access biomechanical properties.
Accurate determination of the biomedical properties of connective tissue such as tendons and ligaments is dependent on the accurate measurement of their cross-sectional area (CSA). To date, techniques for determining cross-sectional areas of ligaments and tendons have been less than ideal due to their complex geometries and their deformations under external load. A novel non-destructive technique has been developed for determining the cross-sectional area of tendon by locating the tendon rupture, in which aqueous rapid curing alginate dental molding materials, digital photography and computerized image analysis are utilized. This technique marks tendons and alginate molds at 1 cm interval and then tendons are taken out for tensile test. Real-time video is recorded to locate the position of tendon rupture. The corresponding alginate slice is found and then analysis through computer image processing software to obtain a more accurate CSA at tendon rupture, which can be used to calculate the stress and young's modulus of tendon. The accuracy of this technique has been investigated and comparisons have been made with the alginate un-localization molding technique and ellipse estimation technique. Results show this technique can provide accurate CSA values (within 2%) and great reproducibility (coefficient of variation = 0.8%). The technique is non-destructive, can obtain morphological information of soft tissue and can detect cavities.


Acoustic and perceptual evaluation of laryngeal reinnervation by ansa cervicalis transfer.
To evaluate the acoustic and perceptual results of laryngeal reinnervation with ansa cervicalis to recurrent laryngeal nerve anastomosis. Retrospective study of voice samples from 12 patients with unilateral recurrent laryngeal nerve paralysis, treated with ansa cervicalis to recurrent laryngeal nerve anastomosis. Samples were recorded before surgery and at least 8 months after surgery. The samples were subjected to several acoustic analyses sensitive to paralytic dysphonia, including cepstral peak prominence, noise-to-harmonics ratio, and measures of frequency and amplitude perturbation. The voice samples from the patients were randomized with age- and sex-matched samples from normal subjects and judged by trained listeners for overall dysphonia, roughness, breathiness, asthenia, and strain. The preoperative and postoperative results were compared statistically, and the postoperative results were compared with the matched normal subjects. As a group, the patients showed improvement (P < .05) in cepstral peak prominence, frequency perturbation, and perceptual judgments of overall dysphonia, breathiness, and asthenia. The best results occurred in patients with isolated vocal fold paralysis. The postoperative group as a whole did not improve to the level seen in matched normals. Suboptimal results were seen primarily in patients with untreated laryngeal or extralaryngeal pathology beyond the laryngeal paralysis. These data suggest that laryngeal reinnervation has the potential to bring about a return to normal or near-normal voice in patients with isolated unilateral vocal fold paralysis.


Insights from molecular dynamics and DFT calculations into the interaction of 1,4-benzodiazepines with 2-hydroxypropyl-βCD in a theoretical study.
This study delves into the interaction between benzodiazepine (BZD) drugs and 2-hydroxypropyl-β-cyclodextrin (2HPβCD), a cyclodextrin (CD) known to improve drug delivery and enhance therapeutic outcomes. We find that the 2HPβCD's atoms become more rigid in the presence of chlordiazepoxide (CDP), clonazepam (CLZ), and diazepam (DZM), whereas they become more flexible in the presence of nordazepam (NDM) and nitrazepam (NZP). We also investigated the structure of 2HPβCD and found that loading these drugs increases both the area and volume of the 2HPβCD cavity, making it more suitable for drug delivery. Moreover, this research found that all drugs exhibited negative values for the binding free energy, indicating thermodynamic favorability and improved solubility. The binding free energy order of the BZDs was consistent in both molecular dynamics and Monte Carlo methods, with CDP and DZM having the highest affinity for binding. We also analyzed the contribution of different interaction energies in binding between the carrier and the drugs and found that Van der Waals energy is the primary component. Our results indicate that the number of hydrogen bonds between 2HPβCD/water slightly decreases in the presence of BZDs, but the hydrogen bond's quality remains constant.


Haemophilus spp., an emerging multidrug-resistant sexually transmitted pathogen.
To describe the characteristics of patients with a positive urethral sample for Haemophilus spp. We performed a retrospective study from January 2018 to July 2019 at the Bordeaux university hospital (France) of all urethral samples positive for Haemophilus spp. Haemophilus spp. was isolated in 10 urethral samples from nine patients. The mean age was 33.8 years. Most patients reported having unprotected sex. Haemophilus parainfluenzae was isolated in nine samples, and Haemophilus influenzae in one sample. Antibiotic susceptibility tests were performed in five samples; Haemophilus spp. was always resistant to amoxicillin and tetracycline. One patient had persistent symptoms after treatment for a multidrug-resistant Haemophilus parainfluenzae strain. Haemophilus spp. is a rare pathogen of urethritis. Its responsibility should be considered in case of persistent symptoms. The emergence of multidrug-resistant Haemophilus spp. is becoming problematic.


The importance of tail temperature monitoring during tail-flick test in evaluating the antinociceptive action of volatile anesthetics.
Tail-flick (TF) latency can be influenced by tail-skin temperature (TT), and treatments that raise TT can mimic hyperalgesia on a TF test. As volatile anesthetics can raise TT via heat redistribution, their antinociceptive action can be hidden or obscured in a TF test. We tested the hypothesis that TT monitoring improves the efficiency of TF tests in evaluating the antinociceptive action of volatile anesthetics. The relationship between TT and TF latency was first explored under varied TTs in 12 rats. Then, TT and TF latency were measured before and during isoflurane exposure (1.2%). In the low temperature group (n=6), rats were prewarmed mildly to increase TT during isoflurane exposure. In the high temperature group (n=6), rats were prewarmed enough to prevent a TT increase during isoflurane exposure. There was a highly significant correlation between TT and TF latency, that is, TF latency decreased as TT increased. In the low temperature group, there was a significant increase in TT during isoflurane exposure, while an increase in TF latency did not reach statistical significance. Tail-flick latency corrected by a change in TT showed a significant increase. In the high temperature group, TF latency increased significantly during isoflurane exposure without an increase in TT. Isoflurane inhalation can induce an increase in TT, which can obscure its antinociceptive action as evaluated by a TF test. Monitoring TT during a TF test is important to efficiently evaluate the antinociceptive action of volatile anesthetics.


Sympatholytic effect of clonidine depends on the respiratory phase in rat splanchnic nerve.
Peri-event averaging of the sympathetic nerve discharge was done to measure the magnitude of the sympatholytic effect of the anti-hypertensive drug clonidine during three different phases of the respiratory cycle (inspiration, I; postinspiration, post-I; late expiration, pre-I). Arterial pressure (AP) and discharges of splanchnic sympathetic (SND) and phrenic nerves (PND, onset used for peri-event averaging) were recorded in urethane-anesthetized, vagotomized, aortic deafferentated, paralyzed and artificially ventilated Sprague-Dawley rats (n = 7). During control periods (mean AP 106 +/- 10 mmHg) SND was distributed equally throughout the three selected respiratory periods, though two brief peaks were noted during the I and post-I periods. Low doses of clonidine (15-30 micrograms/kg i.v.) produced brief hypertension (< 30 s, 150 +/- 9 mmHg at peak) followed by moderate hypotension (89 +/- 3 mmHg) and a reduction in mean SND (-63 +/- 11% from control value). High doses of clonidine (200-250 micrograms/kg i.v.) produced sustained hypertension (> 10 min, 173 +/- 3 mmHg) and silence of SND. During this sustained hypertension, lowering AP by i.v. nitroprusside retrieved a component of SND that was barosensitive but insensitive to clonidine. During those hypotensive periods (spontaneous after a low dose of clonidine, and induced by nitroprusside after a high dose of clonidine), SND was most attenuated during the pre-I period and least during the I period. The I component of SND was significantly less attenuated than the post-I component by clonidine and, in most cases (6 out of 7), SND showed a single inspiratory peak following clonidine administration. It is concluded that (i) the pre-I component of SND is the most sensitive to clonidine and (ii) the I component of SND is the most resistant to the drug.


Richter syndrome first manifesting as cutaneous B-cell lymphoma clonally distinct from primary B-cell chronic lymphocytic leukaemia.
Richter syndrome (RS) is a transformation to high-grade non-Hodgkin lymphoma in patients with chronic lymphocytic leukaemia (CLL). RS may develop in lymph nodes or rarely extranodally. Skin localization of RS has been described in only a few cases. We present a 77-year-old woman who developed isolated diffuse large B-cell lymphoma (LBCL) in the skin of the nose without any other symptoms of RS. The LBCL in the skin was clonally distinct from the original bone marrow CLL cells. Moreover, LBCL cells were positive for LMP-1 segment of Epstein-Barr virus and overexpressed p53 protein. The patient was successfully treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) and adjuvant local radiotherapy.


Virological response to entecavir reduces the risk of liver disease progression in nucleos(t)ide analogue-experienced HBV-infected patients with prior resistant mutants.
This study investigated the influence of virological response (VR) to entecavir on clinical liver disease progression in nucleos(t)ide analogue (NA)-naive and -experienced patients. We investigated 487 chronic hepatitis B patients (323 NA-naive, 164 NA-experienced) treated with entecavir monotherapy for at least 12 months. VR was defined as hepatitis B virus DNA level <300 copies/mL during entecavir therapy. Clinical events were defined as hepatic decompensation, hepatocellular carcinoma (HCC), death and liver transplantation. Of the 487 patients, 49 developed clinical events during entecavir treatment. Of those, 36 developed HCC. For all patients, Cox regression analysis showed that age, baseline cirrhosis, alanine aminotransferase level ≤200 U/L, albumin level and no VR during entecavir treatment were independent predictors for clinical events and HCC development. However, the benefit of VR to entecavir was significant for clinical events and HCC only in NA-experienced patients, but not in NA-naive patients. For the further analysis of the different subgroups of NA-experienced patients, the benefit of VR to entecavir was significant for clinical events or HCC only in patients with prior lamivudine- or adefovir-resistant mutants, but not in NA-experienced patients who had never developed lamivudine- or adefovir-resistant mutants. VR at month 12 (but not early VR at month 6) remained a significant predictor associated with the development of clinical events and HCC in NA-experienced patients. VR to entecavir was associated with a reduced risk of clinical events and HCC in NA-experienced patients, particularly in those who had prior lamivudine- or adefovir-resistant mutants.


Multiple regulation of peptide YY secretion in the digestive tract.
In the last two decades, multiple aspects of the peptide YY (PYY) secretion have been investigated. Besides fat and fatty acids, many luminal nutrients in the distal intestine appear to induce PYY release. Some studies have shown that bile acid, but not nutrients, plays a crucial role in the regulation of PYY secretion. Moreover, chyme in the proximal intestine also regulates the peptide release by indirect action through humoral and neuronal factors. Gastrin, cholecystokinin, and the vagus nerve are major candidates for mediators of these indirect actions. Several growth factors have been shown to regulate PYY synthesis in mucosa of the distal intestine. This review is aimed at presenting an overview of these recent studies on PYY secretion in the distal intestine.


NaCl enhances cellular cAMP and upregulates genes related to heterocyst development in the cyanobacterium, Anabaena sp. strain PCC 7120.
Cellular cAMP was rapidly increased in the nitrogen-fixing cyanobacterium, Anabaena sp. PCC 7120, by the addition of 200 mM NaCl to the culture medium. Other alkaline-metal chlorides such as KCl or LiCl caused a lesser increase. The increase in cellular cAMP was transient and diminished when an adenylate cyclase, CyaC, which contains the conserved domains of the bacterial two-component regulatory system, was disrupted. DNA microarray analysis showed that expression of a gene cluster containing all5347 and alr5351 (hglE) was upregulated by NaCl in the wild-type strain but not in the cyaC mutant. Primer extension analysis indicated that transcription levels of all5347 and hglE were rapidly increased in response to the NaCl addition, and that these genes have NaCl-dependent transcription start sites. It was concluded that NaCl induced expression of genes related to heterocyst envelope formation in this cyanobacterium, possibly via a CyaC-cAMP signal transduction system.


The effect of propranolol and phentolamine on serum gastrin concentration in response to respiratory acidosis in normal man.
Serum gastrin concentration and basal acid secretion were studied in normal subjects under the influence of respiratory acidosis induced by CO2 rebreathing. During the intragastric instillation of 100 ml/h 0.5 M bicarbonate a significant increase of gastrinaemia from 133 to 158 pg/ml (p less than 0.01) occurred in ten subjects during respiratory acidosis (pCO2 62 torr, pH 7.25). Under the intragastric instillation of 100 ml/h 0.1 N HCl the rise of gastrin concentration in response to CO2 rebreathing (pCO2 68 torr, pH 7.20) was not significant. The relationship between the decrease of pH and the increase of the gastrin concentration was shifted in the direction of a greater systemic acidosis compared to the results performed in the presence of a neutral intragastric pH. 50 mug/kg propranolol intravenously produced a decrease of gastrin concentrations from 145 to 127 pg/ml (p less than 0.01) and a total suppression of hypergastrinaemia in response to CO2 rebreathing, suggesting activation of beta-cell receptors in respiratory acidosis. The infusion of phentolamine in a dose of 0.6 to 1.8 mg/min. resulted in a rise of gastrin concentration from 140 to 165 pg/ml (p less than 0.01) which was not further elevated during respiratory acidosis. The basal acid secretion showed a significant rise in response to CO2 rebreathing, which was abolished by the administration of propranolol.


Some studies on the release of histamine from mast cells treated with polymyxin.
Polymyxin B produced a dose-dependent release of histamine from rat peritoneal mast cells. The response was non-cytotoxic and extremely rapid. The release was maximal in the presence of extracellular calcium ions but a substantial component persisted in the absence of the cation. This component was virtually abolished by pretreatment with the ionophore A23187 in the presence of a chelating agent and thus probably reflected the mobilization of intracellular stores of calcium. Hamster peritoneal cells also responded to polymyxin but were less reactive than those of the rat. Mouse peritoneal cells and guinea-pig lung mast cells responded only at very high concentrations. These results further emphasize the functional heterogeneity of mast cells from different sources. Histamine release from rat peritoneal mast cells was inhibited in dose-dependent fashion by cAMP analogues and anti-allergic drugs. The inhibitory effect varied inversely with the magnitude of the control secretion. With the exception of disodium cromoglycate, the test drugs were essentially equiactive in the presence and absence of extracellular calcium. These results are discussed in terms of the possible mode of action of these compounds.


Weight suppression in bulimia nervosa: relationship with cognitive behavioral therapy outcome.
In light of prior inconsistent findings, this study revisits the relationship between weight suppression and treatment outcome in bulimia nervosa. Aside from differences in methodology, we propose that moderator effects may assist the field in interpreting previous inconsistency. In this study, we considered moderators that might place individuals at risk of broad cognitive and biobehavioral mechanisms implicated in weight (dys)regulation and binge eating, and that within the context of a history of weight suppression, might be associated with especially poor outcomes. Participants were 117 female outpatients aged 16-54 years (M = 25.5) with bulimic disorders treated with enhanced cognitive behavioral therapy. Logistic regression indicated that higher pretreatment weight suppression did not predict drop-out or poor treatment outcome (nonabstinence from binging and purging). Moderators of parental history of overweight, childhood body shape, pretreatment body mass index, and the difference between highest and lowest ever adult body weight were analyzed, but no moderator effects were apparent. This study, along with other negative studies, calls into question the association between weight suppression and treatment outcome. We maintain that moderators may account for inconsistencies, but no candidates were identified in this study. Moderator models could assist us to refine conceptualizations of why some patients high in weight suppression may be vulnerable to poor treatment adherence and outcome and to establish clinical interventions that enhance prognosis.


[Effect of sarcolysine on glutathione peroxidase and glutathione reductase activity in sarcoma C-45].
A drop of glutathione peroxidase and glutathione reductase activity was revealed in sarcoma C-45 at the period of its most intensive growth. Repeated sarcolysine injections (1.2 mg/kg, intraperitoneally) caused a sharp fall in the activity of both enzymes with a simultaneous reduction of the ratio of glutathione reductase and glutathione peroxidase activities. The important role of the glutathione enzyme redox system in the realization of antitumour action of the chemotherapeutic drugs is supposed.


Adsorption of toxic dye Eosin Y from aqueous solution by clay/carbon composite derived from spent bleaching earth.
The environmentally friendly clay/carbon composite (SBE/C) was prepared by one-step pyrolysis under N2 atmosphere at 700°C of spent bleaching earth (SBE) from the industrial waste of the refined oil industry. SBE/C was tested to remove anionic dye Eosin Y from aqueous water. The results revealed that SBE/C had larger specific surface area than SBE, and the equilibrium adsorption capacity of SBE/C (11.15 mg/g) was about 3 times than that of SBE (4.04 mg/g). The adsorption process was found to be exothermic and spontaneous. The adsorption capacity of SBE/C was independent on pH (5-12), and exhibits satisfactorily recyclable performance. Combined with characterization analysis, the adsorption mechanism likely includes electrostatic interaction, hydrogen bonding, hydrophobic interaction, halogen bonding, and π-π interaction. Overall, this exploration of SBE/C might open a window to the design of an efficient and low-cost adsorbent for Eosin Y dye elimination from wastewater. PRACTITIONER POINTS: The resource utilization of industrial waste SBE was achieved. SBE/C was synthesized and tested to adsorb Eosin Y for the first time. SBE/C had characteristics with porous structure and large surface area. pH had little effect on adsorption capacity of SBE/C for Eosin Y. SBE/C exhibited potential for dye elimination from wastewater.


Key clinical issues in renal cancer: a challenge for proteomics.
Renal cancer has many clinical challenges which proteomics is ideally placed to address. The issues cover all aspects of the disease including diagnosis, prognosis, treatment selection and monitoring to detect metastatic disease. In all cases novel biomarkers would considerably help in clinical management and with the relative resistance to conventional chemotherapy and radiotherapy, a better understanding of the underlying pathogenesis may contribute to the much needed development of novel therapeutic targets and the better use of promising new anti-angiogenic treatments. This review briefly highlights some of the clinical issues and describes proteomics-based approaches generally, before focussing on reviewing the proteomic studies to date in this area.


The (pro)renin receptor: an emerging player in hypertension and metabolic syndrome.
The (pro)renin receptor (PRR) is a multifunctional protein that is expressed in multiple organs. Binding of prorenin/renin to the PRR activates angiotensin II-dependent and angiotensin II-independent pathways. The PRR is also involved in autophagy and Wnt/ß catenin signaling, functions that are not contingent on prorenin binding. Emerging evidence suggests that the PRR plays an important role in blood pressure regulation and glucose and lipid metabolism. Herein, we review PRR function in health and disease, with particular emphasis on hypertension and the metabolic syndrome.


Long-Term Efficacy of Constant Current Deep Brain Stimulation in Essential Tremor.
Ventralis intermedius deep brain stimulation is an established intervention for medication-refractory essential tremor. Newer constant current stimulation technology offers theoretical advantage over the traditional constant voltage systems in terms of delivering a more biologically stable therapy. There are no previous reports on the outcomes of constant current deep brain stimulation in the treatment of essential tremor. This study aimed to evaluate the long-term efficacy of ventralis intermedius constant current deep brain stimulation in patients diagnosed with essential tremor. Essential tremor patients implanted with constant current deep brain stimulation for a minimum of three years were evaluated. Clinical outcomes were assessed using the Fahn-Tolosa-Marin tremor rating scale at baseline and postoperatively at the time of evaluation. The quality of life in the patients was assessed using the Quality of Life in Essential Tremor questionnaire. Ten patients were evaluated with a median age at evaluation of 74 years (range 66-79) and a mean follow up time of 49.7 (range 36-78) months since starting stimulation. Constant current ventralis intermedius deep brain stimulation was well tolerated and effective in all patients with a mean score improvement from 50.7 ± 5.9 to 17.4 ± 5.7 (p = 0.0020) in the total Fahn-Tolosa-Marin rating scale score (65.6%). Furthermore, the total combined mean Quality of Life in Essential Tremor score was improved from 56.2 ± 4.9 to 16.8 ± 3.5 (p value = 0.0059) (70.1%). This report shows that long-term constant current ventralis intermedius deep brain stimulation is a safe and effective intervention for essential tremor patients.


Quality of obstetric and newborn care in health centers of Addis Ababa City: using the WHO quality framework.
The study aims to assess the quality of obstetric and newborn care using the WHO quality framework. The study used explanatory sequential mixed methods design. This study was conducted in 50 health centers in Addis Ababa city administration from January 25 to December 31, 2021. A total of 50 health centers were surveyed using a structured questionnaire and 500 women in the postpartum period were interviewed using a structured questionnaire. Delivery records of the 500 women were reviewed using a structured checklist. A total of 338 midwives were interviewed using a structured questionnaire. The quantitative data was analyzed using Statistical Package for Social Sciences (SPSS). The study revealed that only a third of the 50 health centers were providing good quality care (a quality score ≥ 75%). All the health centers had the physical resources (100%) to deliver obstetric and newborn care. The majority of the health centers had a system for actionable information (92%), functional referral (80%), and providing dignified care (80%). On the other hand, only a few of the health centers met the quality threshold for effective communication (24%), evidence-based practice of routine obstetric and newborn care (36%), and availability of mechanisms to support and motivate skilled birth attendants (24%). None of the health centers met the quality threshold for emotional support during labour and delivery. Obstetric caregivers' high workload and job dissatisfaction were barriers to quality care. Ensuring quality obstetric and newborn care needs effective quality improvement interventions that aim to ensure women had effective communication, emotional support, and dignity during labour and delivery. Reducing the workload and increasing motivation of birth attendants play a critical role in improving the quality of care.


Prescribing patterns and pharmacoeconomic analysis of antihypertensive drugs in South Indian population: A cross-sectional study.
Global evidence-based recommendations for hypertension management are periodically updated, and ensuring adherence to the guidelines is imperative. Furthermore, the current high prevalence of hypertension effectuates a high health-care cost. To evaluate the prescribing patterns of antihypertensive drugs and other factors affecting blood pressure (BP) with the objective of assessing the proportion of patients achieving the target BP and to perform a pharmacoeconomic analysis in a South Indian population. In a cross-sectional study, 650 patients previously diagnosed with hypertension and already on treatment with one or more drugs were included. A prospective interview of patients was done using a prevalidated questionnaire on various factors in BP control. Prescribing patterns and pharmacoeconomic analyses, namely, cost acquisition, cost of illness, and cost-effectiveness analyses were carried out. Of 650 subjects, 257 (39.54%) achieved the target BP, while 393 (60.46%) did not. A significant association of age, occupational status, monthly family income, and area of residence in addition to physical activity and diet scores, with achieving target BP was noted. A significantly higher cost of anti-hypertensive drug treatment in achieving target BP (P = 0.02) was observed. Among patients who achieved target BP, 37.35% were on monotherapy and 48.25% on multiple drug therapy compared to 46.31% and 35.62%, respectively, in patients who did not. Average cost-effectiveness ratio were found to be Rs. 20.45 and Rs. 57.27, respectively, for single and multiple drug therapies, with incremental cost-effectiveness of Rs. 194.14 per additional patient treated with multiple free drug combinations. This study identified the anti-hypertensive prescribing pattern and provided insight into the various pharmacoeconomic factors that play a significant role in attaining target BP in the treated population.


Liquid nitrogen storage of yeast cultures. I. Survival, and literature review of the perservation of fungi at ultralow temperatures.
All 20 yeast strains of 17 species tested survived 75 days (the length of the experimental period) in liquid nitrogen at -196 C. The components of the more protective of the two freezing media used were (w/v) malt extract 2.5%, yeast extract 0.25%, peptone 0.5%, calf serum 15% (v/v) and dimethyl sulfoxide 10% (v/v). Viability of the cells in this medium after rapid uncontrolled freezing and thawing in selaed plastic ampoules ranged from 2% to 98% (average 67%) compared with the viability of the cultures before freezing. In only 4 strains was survival lower than 50%. (90 references).


Acute systemic embolism due to an idiopathic floating thrombus of the thoracic aorta: success of medical management: a case report.
Idiopathic thoracic aortic mural thrombi are rare. They can be responsible for dramatic systemic embolization. Early treatment is imperative because of their high morbidity and mortality rate. A 55-year-old previously healthy Moroccan male came in an array of acute right lower limbs pain and abdominal sensibility. Severe systemic embolism involving the lower extremities, spleen, kidney, and digestive tract, due to an idiopathic mural thrombus of the thoracic aorta was diagnosed. He received medical treatment leading to the complete disappearance of the thrombus and the effects caused by the latter. When faced unexplained peripheral embolization, research for a thrombus of the thoracic aorta should be performed. Medical treatment should be considered for its management, especially in patients with high surgical risk.


Rapid affinity purification processes for cyclodextrin glycosyltransferase from Bacillus circulans.
Two rapid and easy-to-scale-up methods for the purification of cyclodextrin glycosyltransferase (CGTase) from Bacillus circulans were developed: affinity precipitation with starch and aqueous two-phase partition. The first method, optimised by a factorial design, gave an 80% CGTase adsorption at 11% starch and 1.6% ammonium sulphate, and a 65% recovery after elution with 10 mM alpha-cyclodextrin. The purification factor was 17. Aqueous two-phase partition yielded a 72% CGTase recovery in a two-step procedure; CGTase was obtained in the bottom phase with a purification factor of 37.


Optimal transport improves cell-cell similarity inference in single-cell omics data.
High-throughput single-cell molecular profiling is revolutionizing biology and medicine by unveiling the diversity of cell types and states contributing to development and disease. The identification and characterization of cellular heterogeneity are typically achieved through unsupervised clustering, which crucially relies on a similarity metric. We here propose the use of Optimal Transport (OT) as a cell-cell similarity metric for single-cell omics data. OT defines distances to compare high-dimensional data represented as probability distributions. To speed up computations and cope with the high dimensionality of single-cell data, we consider the entropic regularization of the classical OT distance. We then extensively benchmark OT against state-of-the-art metrics over 13 independent datasets, including simulated, scRNA-seq, scATAC-seq and single-cell DNA methylation data. First, we test the ability of the metrics to detect the similarity between cells belonging to the same groups (e.g. cell types, cell lines of origin). Then, we apply unsupervised clustering and test the quality of the resulting clusters. OT is found to improve cell-cell similarity inference and cell clustering in all simulated and real scRNA-seq data, as well as in scATAC-seq and single-cell DNA methylation data. All our analyses are reproducible through the OT-scOmics Jupyter notebook available at https://github.com/ComputationalSystemsBiology/OT-scOmics. Supplementary data are available at Bioinformatics online.


Posterior microphthalmos with achievement of good visual acuity and disappearance of papillomacular retinal folds: a case report.
Posterior microphthalmos (PM) is a rare condition with poor visual prognosis even after amblyopia treatment. We report a case of PM with achievement of good visual acuity and disappearance of papillomacular retinal folds (PFs) over a period of 7 years. A girl aged 3 years and 5 months was referred to our hospital, after poor visual acuity was identified at a medical checkup for 3-year-olds. She had severe spherical hyperopia: + 17.25 D in the right eye (RE) and + 18 D in the left eye (LE). Her corrected visual acuity was 20/200 in the RE and 20/250 in the LE. PFs were observed in both eyes on optical coherence tomography (OCT), and the diagnosis of PM was made based on the normal corneal diameter and anterior chamber depth. During the course of the disease, a gradual decrease in the height of the PFs was observed on OCT. The corrected visual acuity at age 10 years was 20/20 in the RE and 20/25 in the LE. The visual prognosis of PM is poor, and only one case with good visual acuity has been reported in the literature. The patient in the present case not only developed good visual acuity, but also showed improvement in macular morphology, which was not noted in previous reports. Early diagnosis of PM and early amblyopia treatment is important for the visual development in PM.


Antioxidant and prooxidant properties of mitochondrial Coenzyme Q.
Coenzyme Q is both an essential electron carrier and an important antioxidant in the mitochondrial inner membrane. The reduced form, ubiquinol, decreases lipid peroxidation directly by acting as a chain breaking antioxidant and indirectly by recycling Vitamin E. The ubiquinone formed in preventing oxidative damage is reduced back to ubiquinol by the respiratory chain. As well as preventing lipid peroxidation, Coenzyme Q reacts with other reactive oxygen species, contributing to its effectiveness as an antioxidant. There is growing interest in using Coenzyme Q and related compounds therapeutically because mitochondrial oxidative damage contributes to degenerative diseases. Paradoxically, Coenzyme Q is also involved in superoxide production by the respiratory chain. To help understand how Coenzyme Q contributes to both mitochondrial oxidative damage and antioxidant defences, we have reviewed its antioxidant and prooxidant properties.


General and Eating Disorder Psychopathology in Relation to Short- and Long-Term Weight Change in Treatment-Seeking Children: A Latent Profile Analysis.
Concurrent general psychopathology (GP) and eating disorder psychopathology (EDP) are commonly reported among youth with overweight/obesity and may impact weight change. We identified patterns of GP and EDP in children with overweight/obesity and examined the impact on weight change following family-based behavioral obesity treatment (FBT) and maintenance interventions. Children (N = 172) participated in 4 month FBT and subsequent 8 month weight maintenance interventions. GP and EDP were assessed prior to FBT (baseline). Child percentage overweight was assessed at baseline, post-FBT (4 months), and post-maintenance (12 months). Latent profile analysis identified patterns of baseline GP and EDP. Linear mixed-effects models examined if profiles predicted 4- and 12-month change in percentage overweight and if there were two-way and three-way interactions among these variables, adjusting for relevant covariates. Results indicated a three-profile structure: lower GP and EDP (LOWER); subclinically elevated GP and EDP without loss of control (LOC; HIGHER); and subclinically elevated GP and EDP with LOC (HIGHER + LOC). Across profiles, children on average achieved clinically meaningful weight loss (i.e., ≥9 unit change in percentage overweight) from baseline to 4 month FBT and sustained these improvements at 12 month maintenance. There was no evidence that latent profiles were related to percentage overweight change from baseline to FBT (p > .05) or baseline to maintenance (p > .05). There was no evidence for two-way or three-way interactions (p > .05). Concurrent GP and EDP do not portend differential short- or long-term weight change following FBT and maintenance. Future research is warranted on the durability of weight change among youth with GP and EDP. NCT00759746.


Juvenile elastoma: a forme fruste of the Buschke-Ollendorff syndrome?
We describe an Asian child with juvenile elastoma who presented to us at 9 years of age with flesh-coloured nodules on his thigh. Histologically, H&E sections were normal, but elastin stains showed collections of increased and thickened elastic fibres consistent with juvenile elastoma. Radiological examination did not demonstrate osteopoikilosis. However, we postulate that he may represent a forme fruste of the Buschke-Ollendorff syndrome or early presentation prior to the subsequent development of osteopoikilosis.


The Ideal Hinge Axis Position to Reduce Tibial Slope in Opening-Wedge High Tibial Osteotomy Includes Proximalization-Extension and Internal Rotation.
To evaluate the effect of the hinge axis position on the posterior tibial slope (PTS) in medial opening-wedge high tibial osteotomy. This study included adults with medial-compartment osteoarthritis who had computed tomography (CT) scans available that were amenable to Bodycad Osteotomy software analysis. Virtual osteotomies modeling a 10-mm medial opening-wedge gap were performed. The hinge axis was rotated internally and externally and was proximalized-extended and distalized-flexed with respect to the anterior tibial cortex for 5°, 10°, 15°, and 20°. Each resultant PTS was recorded and compared with the results obtained from the true lateral hinge position and with the preoperative PTS. Computed tomography scans from 10 patients were used. Strong linear correlations were found with each hinge axis position change and the resultant PTS. The trend-line differences were statistically significant by single-factor analysis of variance (P < .001). The PTS decreased for an anterolateral hinge, whereas it increased for a posterolateral hinge. Linear regression analysis showed that rotating the hinge axis by 9.0° externally or angulating the hinge axis by 21.8° of distalization-flexion would result in increasing the tibial slope by 1° whereas rotating the hinge axis by 8.7° internally or angulating the hinge axis by 21.6° of proximalization-extension would decrease the tibial slope by 1°. Distalization-flexion and external rotation of the hinge axis position led to stepwise increases in the PTS, whereas proximalization-extension and internal rotation led to decreases in the PTS. Our findings suggest that when performing medial opening-wedge high tibial osteotomy and aiming to decrease the PTS, the surgeon should aim to achieve maximal internal rotation (producing an anterolateral hinge), as well as proximalization-extension, of the hinge axis. This study quantifies and provides a model for the effect of the hinge axis position for a predetermined angular correction on the PTS.


The Present and Future of Neoadjuvant and Adjuvant Therapy for Locally Advanced Gastric Cancer.
Gastric cancer is a highly prevalent and lethal disease worldwide. Given the insidious nature of the presenting symptoms, patients are frequently diagnosed with advanced, unresectable disease. However, many patients will present with locally advanced gastric cancer (LAGC), which is often defined as the primary tumor extending beyond the muscularis propria (cT3-T4) or having nodal metastases (cN+) disease and without distant metastases (cM0). LAGC is typically treated with surgical resection and perioperative chemotherapy. The treatment of LAGC remains a challenge, given the heterogeneity of this disease, and the optimal multimodal treatment regimen may be different for different LAGC subtypes. However, many promising treatments are on the horizon based on knowledge of molecular subtypes and key biomarkers of LAGC, such as microsatellite instability, HER2, Claudin 18.2, FGFR2, and PD-L1. This review will expand upon the discussion of current standard neoadjuvant and adjuvant therapies for LAGC and explore the ongoing and future clinical trials for novel therapies, with information obtained from searches in PubMed and ClinicalTrials.gov.


Estimating asymptotic size using the largest individuals per sample.
Estimates of asymptotic size are especially useful for comparative studies of taxonomic groups in which animals mature at small sizes relative to their final asymptotic sizes. The largest individuals per sample can provide reasonable estimates of asymptotic size if three conditions are met: 1) at least some adults in a population are near their final asymptotic size, 2) samples of a reasonable size are likely to contain a 'largest individual' that is near the average asymptotic size for the members of its sex, and 3) the coefficient of variation in asymptotic size is small for the members of each sex. In the current study, we show that all three of these conditions are met for one species of Anolis lizards (A. limifrons). For a series of samples from the genus Anolis, the largest individual per sample produces estimates of asymptotic size that are virtually identical to those produced by fitting field data on growth rates to nonlinear growth equations. These results suggest that the largest individual method can provide reasonable estimates of asymptotic size for the members of this genus, and imply that this method may also be useful for estimating asymptotic sizes in other taxa that satisfy the criteria listed above.


[68Ga]PSMA PET/CT Improves Initial Staging and Management Plan of Patients with High-Risk Prostate Cancer.
In this retrospective study, we compared the diagnostic value of 68Gallium prostate-specific membrane antigen positron emission tomography computed tomography ([68Ga]PSMA PET/CT) in primary staging of patients with high-risk prostate cancer (PCa), in comparison to CT, magnetic resonance imaging (MRI), and bone scans, and we explored its overall impact on patients' management plan. Patients with pathological confirmation of PCa with high-risk disease were included in this study. Information on patient demographics, clinical and histopathological findings with Gleason score and initial prostate specific antigen PSA levels, and radiological findings for CT, MRI, bone scan, and [68Ga]PSMA PET/CT were retrieved. We stratified the concordance and discordance of each imaging modality on per-patient and per-lesion-site bases. Twenty-one patients with high-risk disease were included in this study. [68Ga]PSMA PET/CT revealed a significantly higher concordance rate (90 %) compared to the concordance rates of bone scan (75 %), MRI (73 %), and CT (60 %). [68Ga]PSMA PET/CT had a similar accuracy to MRI in detecting prostate lesions but a higher accuracy for suspicious pelvic lymph nodes (95.2 % vs. 80 %). It also superseded CT scan in detecting suspicious pelvic lymph nodes (95.2 % vs. 75 %) and extra-pelvic lymph nodes (100 % vs. 75 %), as well as bone lesions via bone scan (100 % vs. 62.5 %). [68Ga]PSMA PET/CT changed the management in 11 patients (52 %). [68Ga]PSMA PET/CT is an invaluable imaging modality in the assessment of primary high-risk PCa with great potential for the detection of lymph node spread and bone metastases that would impact the management plan.


A novel anteroposterior axis of the tibia for total knee arthroplasty: An upright weight-bearing computed tomography analysis.
The traditional anteroposterior (AP) axis (i.e., Akagi's line) has been widely used as the tibial component AP axis during total knee arthroplasty (TKA). However, this AP axis has been defined based on computed tomography (CT) in a non-weight-bearing supine position. In this study, AP axes of the tibial plateau from upright CT in weight-bearing and non-weight-bearing positions were determined and compared. This study included 43 knees from 23 healthy volunteers. CT images were obtained in weight-bearing and non-weight-bearing standing positions using a 320-detector row upright CT scanner. The line perpendicular to surgical transepicondylar axis projected onto the tibia plateau was determined as the AP axis in upright weight-bearing and non-weight-bearing conditions. Angular differences between these two conditions were measured. The upright weight-bearing AP axis was positioned in a mean of 7.4 ± 4.3° of internal rotation relative to the traditional AP axis. Distance between the traditional and upright weight-bearing AP axis was 2.9 ± 1.6 mm at the edge of the tibial plateau. The upright non-weight-bearing AP axis was positioned in a mean of 3.5 ± 4.1° of internal rotation relative to the traditional AP axis. Mean angular difference between weight-bearing and non-weight-bearing conditions was 3.9 ± 4.1°. The upright weight-bearing AP axis was positioned in 7.4° of internal rotation relative to the traditional AP axis, showing one-seventh of the tibial tuberosity away from the medial border of the tibial tubercle, which represents a practical landmark for the tibial component AP axis during TKA.


[The effect of blood-pancreatic juice barrier on 5-fluorouracil in post-pancreatoduodenectomy patients].
To observe the distribution and the relationship of 5-Fu in the plasma and the pancreatic juice in post-pancreatoduodenectomy patients after 5-Fu given intravenously. After 5-Fu (1.0 g/m(2)) was given intravenously in post-pancreatoduodenectomy patients, blood and pancreatic juice were collected. The 5-Fu concentrations were determined by HPLC and at last the penetration ratio (PR) of 5-Fu was studied with PCNONLIN. 5-Fu in the plasma penetrated the pancreatic tissue and crossed the blood-pancreatic juice barrier (BPJB) in post-pancreatoduodenectomy patients (PR = 1.01 +/- 0.49). The concentration of 5-Fu in pancreatic juice was much higher than that in plasma. 5-Fu is suitable for adjuvant chemotherapy of pancreatic adenocarcinoma after pancreatoduodenectomy.


Transatrial approach of acquired posterior ventricular septal rupture and double orifice technique in tricuspid valve repair.
We present a successful transatrial repair of ventricular septal rupture and tricuspid valve reconstruction, using the "edge-to-edge" technique, as a serious complication of a posterior myocardial infarction in an 83-year-old woman.


Hepatic arterial embolization utilizing a coaxial catheter system: technical note.
A coaxial catheter system using the Tracker Hi-Flow catheter was utilized to perform 38 hepatic arterial embolizations in 20 patients. These embolizations would not have been feasible if the ability to superselectively catheterize the segmental arteries and negotiate tortuous vessels had not been available. This is a valuable technique for use in superselective hepatic arterial embolizations.


Diastolic mitral regurgitation in acute but not chronic aortic regurgitation: implications regarding the mechanism of mitral closure.
In acute aortic regurgitation, left ventricular pressure rises rapidly during diastole, which produces presystolic mitral valve closure. This does not occur in chronic aortic regurgitation. Since normal, nonregurgitant mitral valve closure may depend on properly coordinated atrial and ventricular contractions, we hypothesized that abnormal mitral valve closure occurring before systole in acute aortic regurgitation may produce diastolic mitral regurgitation detectable by Doppler echocardiography. Accordingly, we performed ultrasonic Doppler examination of seven patients with acute aortic regurgitation and 12 patients with chronic aortic regurgitation. Regurgitant aortic flow was severe in all cases. Doppler sampling within the left atrium demonstrated regurgitant mitral flow in late diastole in all patients with acute aortic regurgitation. The onset of diastolic mitral regurgitation coincided with mitral valve preclosure in patients with acute aortic regurgitation and occurred regardless of the position of the mitral leaflets at the initiation of closure. In contrast, none of the 12 patients with chronic aortic regurgitation had mitral valve preclosure or diastolic mitral regurgitation (p less than 0.05 versus acute aortic regurgitation). We conclude that diastolic mitral regurgitation accompanies mitral valve preclosure, which occurs in acute but not chronic aortic regurgitation. Thus diastolic mitral regurgitation may be a Doppler sign of acute aortic regurgitation, in the absence of a markedly prolonged PR interval. Furthermore, this observation suggests that normal, nonregurgitant mitral closure requires more than an increase in left ventricular pressure above left atrial pressure, regardless of the position of the mitral leaflets before closure.


Effectiveness of physical activity prescription by primary care nurses using health assets: A randomized controlled trial.
To evaluate the effectiveness of a 12-month multifactorial intervention by primary care nurses using health assets in increasing adherence to physical activity prescription (150 min/week) in patients with two or more cardiovascular risk factors. Physical activity promotion is a priority and helps to decrease mortality risk due to cardiovascular diseases. However, adherence to the habitual physical activity prescription in primary healthcare settings is low. Multicentre, single-blind, parallel randomized (in two different branches) clinical trial. In total, 263 participants from 20 primary healthcare centres in Mallorca completed the randomized controlled trial study (intervention group N = 128, control group N = 135). The intervention consisted in four visits and included a motivational interview and an individualized prescription of physical activity using health assets. Primary outcome measure was the number of participants performing at least 150 min of weekly physical activity. Secondary outcomes included physical activity level and physical fitness, Sense of Coherence, cardiovascular risk, sociodemographic data, trans-theoretical stage of change, sleep quality, and depression. Adherence to the recommendation of at least 150 min of physical activity was higher in the intervention than in the control group (χ2 = 3.951, p = .047). However, this higher adherence did not suppose higher physical activity levels because no differences between groups were found in the total physical activity performed after intervention (t=-0.915, p = .361). At the end of the intervention participants randomized to the intervention group spent more time walking than participants in the control group (t = 2.260, p = .025). The multifactorial intervention performed by primary care nurses induced a higher adherence to the 150-min of weekly physical activity recommendation. Adherence to the usual physical activity prescription in primary care is low. Physical activity prescription performed by primary care nurses and based on health assets and motivational interview can help to increase physical activity levels of patients. The main finding of the present study was that prescription using this approach was shown to be effective, leading to a higher adherence in the intervention group. This intervention is feasible in the nurse's primary healthcare setting, thus it could be implemented as the main tool when exercise is prescribed. International Standard Randomized Controlled Trial Number: ISRCTN76069254.


Stressful delivery influences circulating thrombopoietin (TPO) levels in newborns: possible role for cortisol in TPO-mpl binding.
The regulation mechanism of circulating thrombopoietin (TPO) level in human newborns remains unknown. In the present study, we examined whether the TPO concentrations in cord blood were influenced by the difference in the delivery method and the presence or absence of maternal/fetal complications. Cortisol levels were simultaneously measured to assess the adrenal response of fetuses. Both the TPO level and the cortisol level were substantially greater in the neonates delivered vaginally with and without the complications than in those delivered by cesarean section without the complications. The binding assay showed that the incubation of mpl(+)/BaF3 cells with cortisol gave rise to a significant decrease in the binding sites of TPO. These results suggest that the stress to the fetuses near the time of delivery affects the cord blood TPO levels, which may be mediated in part by the action of cortisol on the TPO-mpl binding system.


[A study on the compound bone morphogenetic protein with chitosan and cyanoacrylate on preventive absorption of rat's alveolar ridge].
To evaluate the effectiveness and feasibility of compound bone morphogenetic protein (BMP) with chitosan and cyanoacrylate on preventive absorption of rat's alveolar ridge. Fifty-four Wistar rats were divided randomly into three groups: Experimental group (compound BMP with chitosan and cyanoacrylate group), control group (chitosan composite group) and blank group. After rat lower incisors were extracted, compound BMP with chitosan and cyanoacrylate were implanted into experimental group rat's residual alveolar fossa, control group implanted with chitosan, blank group left empty. Animals were sacrificed after 3, 6, 9 weeks. X-ray examination, Image-Pro Plus analysis and pathologic observation were evaluated. The relative length values of residual alveolar ridge and optical density test in experimental group were all greater than those of control group and blank group at 3, 6, 9 weeks after operation (P < 0.05). Light microscopy showed that new bone formations in experimental group were better than those in control group and blank group at 3, 6, 9 weeks after implantation. Compound BMP with chitosan and cyanoacrylate can be used to prevent the absorption of residual alveolar ridge and have more clinical predications. [


Preparation of polysaccharide-based nanoparticles by chitosan and flaxseed gum polyelectrolyte complexation as carriers for bighead carp (Aristichthys nobilis) peptide delivery.
Polysaccharide-based nanoparticles formed by the polyelectrolyte complexation between chitosan (CS) and flaxseed gum (FG) was developed in this work, and it was further used as a carrier for bighead carp peptide (BCP) delivery. The CS molecular weight (MW) of 50 kDa and CS/FG mass ratio of 1:2 at pH 3.5 were optimal conditions for the NP preparation, with the minimum particle size (∼155.1 nm) and the maximum BCP encapsulation efficiency (60.3 %). The BCP-loaded CS/FG NPs exhibited the smallest particle size (175.8 nm). Both CS/FG NPs and CS/FG-BCP NPs exhibited roughly uniform spherical shape. FT-IR spectra confirmed the existence of hydrogen bonds and electrostatic interactions in the nanoparticles. The BCP-loaded NPs displayed a higher thermal stability than BCP. Moreover, the release of BCP was controllable and dose-dependent, following a first-order kinetics model. These findings suggested that our CS/FG NPs are a promising carrier for bioactive peptide delivery.


Modulation of reciprocal and presynaptic inhibition during robotic-assisted stepping in humans.
To establish the modulation pattern of reciprocal inhibition and presynaptic inhibition of soleus Ia afferents during robot-assisted stepping in healthy subjects. During stepping, the soleus H-reflex was conditioned by percutaneous stimulation of the ipsilateral common peroneal nerve with a single pulse at stimulation intensities that ranged from 0.9 to 1.2 TA M-wave motor thresholds across subjects. To control for movement of recording and stimulating electrodes, a supramaximal stimulus 80ms after the conditioned and/or unconditioned H-reflexes was delivered to the posterior tibial nerve. The short (2, 3, 4ms) and long (60-80ms) conditioning-test intervals at which the largest amount of reflex depression was observed with the subjects seated were utilized during stepping. Stimuli were randomly dispersed across the step cycle which was divided into 16 equal bins. Reciprocal inhibition exerted from flexor group I afferents onto soleus motoneurons was decreased at mid-stance and increased and late-stance and throughout the swing phase. Presynaptic inhibition of soleus Ia afferents was increased at heel strike and decreased at late-stance and early swing phases. Reciprocal inhibition between ankle antagonistic muscles and presynaptic inhibition of soleus Ia afferents are modulated in a similar pattern to that reported during walking on a treadmill with full weight bearing and without robot-assisted leg movement. The activity of spinal interneuronal circuits engaged in patterned locomotor activity supports a reciprocal gait pattern during robot-assisted stepping in healthy humans.


Cyclosporine A-induced renal fibrosis: a role for epithelial-mesenchymal transition.
Cyclosporine A, which has been the foremost immunosuppressive agent since the early 1980's, significantly improves the success of organ transplantation. However, common complications of cyclosporine A therapy, such as severe renal tubulointerstitial fibrosis, limit the drug's clinical use. Although the exact mechanisms driving cyclosporine A-induced tubulointerstitial fibrosis remain elusive, we hypothesized that epithelial-mesenchymal transition (EMT) may play a major role. We investigated this in vitro by treating human proximal tubular cells with cyclosporine A. Morphological changes were observed after cyclosporine A treatment, including cell elongation (with a large degree of detachment), cytoskeletal rearrangement, and junctional disruption. In addition, expression of the myofibroblast-specific marker alpha-smooth muscle actin was detected in treated cells. These observations are consistent with events described during EMT. Using Affymetrix gene microarrays, we identified 128 genes that were differentially regulated in renal tubular cells after cyclosporine A treatment, including known profibrotic factors, oncogenes, and transcriptional regulators. Cyclosporine A induced a dose-dependent increase in transforming growth factor-beta secretion from proximal tubular cells. Subsequent functional studies revealed that protein kinase C-beta isoforms play a key role in cyclosporine A-induced effects. These findings provide novel insights into cyclosporine A-induced renal fibrosis and the molecular mechanisms underlying EMT, events that may be relevant in other disease states.


2,6-diaminopurine in TNA: effect on duplex stabilities and on the efficiency of template-controlled ligations.
Replacement of adenine by 2,6-diaminopurine-two nucleobases to be considered equivalent from an etiological point of view-strongly enhances the stability of TNA/TNA, TNA/RNA, or TNA/DNA duplexes and efficiently accelerates template-directed ligation of TNA ligands. [reaction: see text]


Body mass index and uterine receptivity in the oocyte donation model.
To evaluate the relationship of body mass index (BMI) to uterine receptivity under conditions of programmed hormonal support and standardized embryo quality. Retrospective cohort study.A tertiary referral center. Ninety-seven consecutive first-cycle recipients of anonymous oocyte donation. After programmed hormone replacement, recipients had transfer of embryos derived from oocyte donation. Anonymous oocyte donors received ovarian stimulation and underwent transvaginal ultrasound-guided oocyte retrieval. A receiver operator characteristic (ROC) curve of implantation versus BMI. Area under the ROC curve was 0.51, 95% confidence interval (CI) 0.41-0.62, suggesting no relationship between BMI and implantation. There was no difference in implantation rates between obese (BMI >or=30) and nonobese (BMI <30) recipients, odds ratio 1.1, 95% CI 0.5-2.4. Uterine receptivity was unimpaired in women with increased BMI when hormonal support and embryo quality were standardized.


Improving Resource Utilization and Outcomes Using a Minimally Invasive Pilonidal Protocol.
The purpose of this study was to evaluate the resource utilization and outcome of a minimally invasive pilonidal protocol (MIPP) versus surgical excision (SE) in adolescents with pilonidal disease. Improved hygiene, laser epilation (LE), and sinusectomy were implemented as a minimally invasive pilonidal protocol (MIPP) in March 2016. Following IRB approval, 34 consecutive MIPP patients with moderate and severe disease were compared with a random sample of 17 SE patients treated prior to MIPP implementation. Number of visits, laser epilation (LE) treatments, care duration, operations, operating room (OR) time, charges, and condition at last visit were analyzed. Charges were standardized for 2018. No differences were found in age or body mass index between groups. SE patients underwent an average 1.6 excisions/patient (cumulative 2598 OR minutes) and no LE. MIPP patients underwent an average 1.4 sinusectomies and 3.5 LEs/patient. Six sinusectomies (0.17/patient) were performed in OR (cumulative 258 OR minutes). No differences in number of visits or care duration were found between groups. At last follow-up, 82% of MIPP and 18% of SE patients were healed or asymptomatic (p < 0.01). Average charges were $29,098 for SE versus $8440 for MIPP (p < 0.01). A minimally invasive pilonidal protocol reduces charges and improves outcome compared with surgical excision in adolescents. III. Retrospective comparative study.


Embryonic stem cells that differentiate into RPE cell precursors in vitro develop into RPE cell monolayers in vivo.
A culture system to generate eye-like structures consisting of lens, neural retina, and retinal pigmented epithelium (RPE) cells from undifferentiated embryonic stem cells has been established. Precursors of RPE cells that differentiated in the cultures were responsive to Wnt2b signaling and identified retrospectively to form secondary colonies consisting of only RPE-like cells in eye-like structures. These transplanted eye-like structures were capable of populating the developing chick eye as neuronal retina and RPE cells. The outgrowth of a single cell layer of mature RPE cells from the grafted eye-like structures confirmed the existence of precursors for RPE cells. These results suggest that the eye-like structures resulted from the normal developmental pathway responsible for generating eyes in vivo. If a functional effect of these cells can be established, such eye-like structures may be potentially used to establish therapy models for various eye diseases.


Observation of an Alice ring in a Bose-Einstein condensate.
Monopoles and vortices are fundamental topological excitations that appear in physical systems spanning enormous scales of size and energy, from the vastness of the early universe to tiny laboratory droplets of nematic liquid crystals and ultracold gases. Although the topologies of vortices and monopoles are distinct from one another, under certain circumstances a monopole can spontaneously and continuously deform into a vortex ring with the curious property that monopoles passing through it are converted into anti-monopoles. However, the observation of such Alice rings has remained a major challenge, due to the scarcity of experimentally accessible monopoles in continuous fields. Here, we present experimental evidence of an Alice ring resulting from the decay of a topological monopole defect in a dilute gaseous 87Rb Bose-Einstein condensate. Our results, in agreement with detailed first-principles simulations, provide an unprecedented opportunity to explore the unique features of a composite excitation that combines the topological features of both a monopole and a vortex ring.


The HIV-1 protease resistance mutation I50L is associated with resistance to atazanavir and susceptibility to other protease inhibitors in multiple mutational contexts.
The HIV-1 protease mutation I50 L causes atazanavir resistance but increases susceptibility to other PIs. Predicted phenotypic FC values were obtained from viral genotypes, using the virtual Phenotype-LM bioinformatics tool (powering vircoTYPE). To evaluate I50 L's effect on susceptibility to 8 PIs, in a large genotype database. I50 L containing routine clinical isolate samples in Virco's genotype database were paired with samples having like patterns (or profiles) of IAS-USA-defined primary PI mutations, but lacking I50 L. Using vircoTYPE (version 4.1), the median predicted FC for each mutational profile was determined. I50 L-associated shifts in FC were evaluated using drug-specific CCOs. We selected 307 and 37098 samples with and without I50 L. These corresponded to 31 mutation patterns of > or =3 samples each. I50 L caused resistance to atazanavir in all 31 mutation contexts, but was associated with higher susceptibility for other PIs. The largest I50 L-associated shifts in median predicted FC were: 1.2 to 42.4 (atazanavir), 10.2 to 3.2 (amprenavir), 3.3 to 0.5 (darunavir), 13 to 0.5 (indinavir), 34.9 to 1.3 (lopinavir), 22.3 to 1.3 (nelfinavir), 5.2 to 0.3 (saquinavir) and 29.9 to 5.2 (tipranavir). The PI mutation I50 L causes clinically relevant resistance and increased susceptibility to atazanavir and other PIs respectively.


Chemical synthesis and formulation design of a PEGylated vasoactive intestinal peptide derivative with improved metabolic stability.
The present study aimed to design a PEGylated VIP derivative, [Arg(15, 20, 21), Leu(17)]-VIP-GRR (IK312532), with improved metabolic stability, and develop its respirable powder (RP) formulation for inhalation therapy. IK312532 was chemically conjugated with PEG (5 kDa, P5K), the physicochemical and biochemical properties of which were characterized by CD spectral analysis, binding assays, and metabolic stability. CD spectral analysis demonstrated that PEG conjugation had no impact on the conformational structure of IK312532. Although the receptor-binding activity of IK312532/P5K (IC₅₀: 82 nM) was estimated to be ca. 30-fold less than that of IK312532 (IC₅₀: 2.8 nM), the metabolic stability of IK312532/P5K was highly improved. The IK312532/P5K was jet-milled and blended with lactose carrier particles to provide RP formulation of IK312532/P5K (IK312532/P5K-RP). In vitro inhalation performance and in vivo pharmacological effects of the IK312532/P5K-RP in antigen-sensitized rats were also evaluated. In cascade impactor analyses, fine particle fraction of IK312532/P5K-RP was calculated to be ca. 37%. Insufflation of IK312532/P5K-RP (150 μg of IK312532/P5K) in antigen-sensitized rats resulted in marked attenuation of inflammatory events, as evidenced by significant decreases in inflammatory biomarkers and granulocyte recruitment in pulmonary tissue 24h after the antigen challenge. From these findings, PEGylation of a VIP derivative, as well as its strategic application to the RP formulation, may be a viable approach to improve its therapeutic potential for the treatment of airway inflammatory diseases.


Measurement of waist circumference at different sites affects the detection of abdominal obesity and metabolic syndrome among psychiatric patients.
There is a lack of understanding about the impact of different waist circumference (WC) measurements on the detection of abdominal obesity and metabolic syndrome in psychiatric patients. This cross-sectional study included a total of 382 inpatients with schizophrenia-related disorders to assess each component of metabolic syndrome. WC was measured at the lowest rib, midpoint between the iliac crest and lowest rib, iliac crest, minimal waist, and umbilicus. Logistic regression analysis was performed to examine the ability of WC at each site to predict the presence of metabolic risk clustering. The mean WC values for all sites were significantly different from each other. The measurement site had an influence on the prevalence of abdominal obesity (30-38.2% in men and 53.9-86.3% in women). The influence on the prevalence of metabolic syndrome was greater with the International Diabetes Federation (IDF) criteria (19.3-23.9% in men and 29.4-43.1% in women) than with the Adult Treatment Panel III (ATP III) criteria (26.1-28.6% in men and 37.3-44.1% in women). The areas under the receiver operating characteristic curve for metabolic risk clustering were highest at the umbilicus and midpoint. Given that the WC measurement protocol has substantial influence on the prevalence of abdominal obesity and metabolic syndrome, a predefined measurement site is required for all psychiatric studies.


[Surgery in the sitting position : anesthesiological considerations].
Surgical interventions in the sitting position are intended to optimize surgical conditions by reducing bleeding in the operation field and improving the surgical approach. There are, however, some potentially life-threatening risks associated with surgery in the sitting position. Of these risks, air embolism is one of the most serious complications and should be detected immediately in order to initiate specific countermeasures. In addition to standard monitoring procedures, transthoracic Doppler ultrasound and transesophageal echocardiography are valuable methods used to detect the presence of air in the vasculature. If an air embolism becomes apparent, further targeted measures are needed to prevent or aggressively treat the progression of potentially life-threatening consequences.


Examination of the reproductive effects of tricresyl phosphate administered to Long-Evans rats.
Tricresyl phosphate (TCP) is used commercially as a plasticizer and a flame retardant. The reproductive effects of TCP (less than 9.0% TOCP) were examined. Male Long-Evans rats received 0, 100, or 200 mg/kg and females received 0, 200, or 400 mg/gk TCP in corn oil by gavage. The 100 mg/kg TCP males were mated with 200 mg/kg TCP females, and 200 mg/kg TCP males were bred with 400 mg/kg TCP females. Males were dosed for 56 days and females for 14 days prior to breeding and throughout the 10-day breeding period. Following breeding, the males were necropsied and evaluated for sperm parameters and reproductive tract histopathology. Females were dosed throughout gestation and lactation. Pups and adult females were necropsied on postnatal day 21. Sperm concentration, motility, and progressive movement were decreased for 200 mg/kg dose group males. A dose-dependent increase in abnormal sperm morphology was observed for males in both TCP dose groups. The percent of sperm-positive females per group was unchanged, but the number of females delivering live young was severely decreased by TCP exposure. Litter size and pup viability were decreased in the 400 mg/kg dose group. Pup body weight and developmental landmarks were unaffected by TCP exposure. Histopathologic changes were observed in the testes and epididymides of male rats and in the ovaries of female rats exposed to TCP.


Induction chemotherapy and radiotherapy in locally advanced non-small cell lung cancer.
The position for induction chemotherapy has shifted somewhat in the past few years. This approach has the ability to reduce distant failure and is relatively easy to administer. There are patients who would benefit from and could be offered induction chemotherapy--specifically, those who would not tolerate concurrent chemoradiotherapy or those who might benefit from more intensive therapy combing induction and concurrent strategies. The latter platform, however, should be undertaken with caution, ideally in a clinical trial setting.


Cognitive ability and decline after early life stress exposure.
We examined the effects of early life stress on cognitive ability and decline among men of the Helsinki Birth Cohort Study, 10% of whom were separated temporarily (mean age at separation = 4.1 years) from their parent(s) during World War II. The men underwent the Finnish Defense Forces Basic Intellectual Ability Test twice, at 20 years and retest at 70 years. Compared with the men without childhood separation and matched for year of birth (n = 186), men separated from their parents (n = 93) scored lower by 5.5 (95% confidence interval [CI], -9.2 to -1.7), 4.2 (95% CI, -8.1 to -0.3), 3.1 (95% CI, -7.0 to 0.8), and 4.5 (95% CI, -10.5 to -1.4) standardized points (SD = 15) on verbal, visuospatial, arithmetic, and general cognitive ability, respectively, at 70 years. Longer duration of separation was associated with lower test scores. Though early life stress was also associated significantly with weaker cognitive performance at the ages 20 and 70 years, it was not associated with cognitive decline over the 50-year period within this sample.


Molecular detection of Coxiella burnetii in small ruminants and genotyping of specimens collected from goats in Poland.
Coxiella burnetii is the etiological agent of Q fever, a zoonosis affecting many animal species including sheep and goats. The aims of this study were to evaluate the shedding of Coxiella burnetii in small ruminant herds and to identify the pathogen's genotypes and sequence types (STs) using multiple-locus variable number tandem repeat analysis (MLVA) and multispacer sequence typing (MST) methods. Overall, 165 samples from 43 herds of goats and 9 flocks of sheep were collected including bulk tank milk (BTM), individual milk samples, vaginal swabs, tissue sections from stillborn kids, feces and placentas. These were tested by real-time PCR targeting the IS1111 element. C. burnetii infection was confirmed in 51.16% of the herds of goats and 22.2% of the flocks of sheep. Six out of nine samples originating from goats were successfully genotyped using the MLVA method. The presence was confirmed of two widely distributed MLVA genotypes (I and J) and genotype PL1 previously reported only in cattle. Only one sequence type (ST61) was identified; however, the majority of specimens represented partial STs and some of them may belong to ST61. Other partial STs could possibly be ST74. This study confirmed the relatively common occurrence of Coxiella burnetii in small ruminant herds in Poland. Interestingly, all genotyped samples represent cattle-associated MLVA genotypes.


The long-term outcome of treated high-risk nonmuscle-invasive bladder cancer: time to change treatment paradigm?
The treatment of high-risk nonmuscle-invasive bladder cancer (NMIBC) is difficult given its unpredictable natural history and patient comorbidities. Because current case series are mostly limited in size, the authors report the outcomes from a large, single-center series. The authors reviewed all patients with primary, high-risk NMIBC at their institution from 1994 to 2010. Outcomes were matched with clinicopathologic data. Patients who had muscle invasion within 6 months or had insufficient follow-up (<6 months) were excluded. Correlations were analyzed using multivariable Cox regression and log-rank analysis (2-sided; P < .05). In total, 712 patients (median age, 73.7 years) were included. Progression to muscle invasion occurred in 110 patients (15.8%; 95% confidence interval [CI], 13%-18.3%) at a median of 17.2 months (interquartile range, 8.9-35.8 months), including 26.5% (95% CI, 22.2%-31.3%) of the 366 patients who had >5 years follow-up. Progression was associated with age (hazard ratio [HR], 1.04; P = .007), dysplastic urothelium (HR, 1.6; P = .003), urothelial cell carcinoma variants (HR, 3.2; P = .001), and recurrence (HR, 18.3; P < .001). Disease-specific mortality occurred in 134 patients (18.8%; 95% CI, 16.1%-21.9%) at a median of 28 months (interquartile range, 15-45 months), including 28.7% (95% CI, 24.5%-33.3%) of those who had 5 years of follow-up. Disease-specific mortality was associated with age (HR, 1.1; P < .001), stage (HR, 1.7; P = .003), dysplasia (HR, 1.3; P = .05), and progression (HR, 5.2; P < .001). Neither progression nor disease-specific mortality were associated with the receipt of bacillus Calmette-Guerin (P > .6). Within a program of conservative treatment, progression of high-risk NMIBC was associated with a poor prognosis. Surveillance and bacillus Calmette-Guerin were ineffective in altering the natural history of this disease. The authors concluded that the time has come to rethink the paradigm of management of this disease.


Horst Otto Stoeckel: Collector and Museum Founder.
As a medical student and during his preacademic time prior to 1958, Horst Stoeckel was interested in the history of medicine and especially history related to anesthesia. After his retirement from Chair of Anesthesiology at the University of Bonn in 1994, Stoeckel received a gift from Professor Richard Kitz of Harvard University (Boston, MA) that encouraged him to develop his collection of 150 artifacts and 350 books and periodicals into a scientific museum and library. The late librarian, Patrick P. Sim, MLS, of the Wood Library-Museum of Anesthesiology in the United States also encouraged and supported Stoeckel with literature concerning anesthesia history. The Horst Stoeckel Museum of Anaesthesiology (Horst-Stoeckel-Museum fur die Geschichte der Anasthesiologie) was dedicated by the University of Bonn and opened to the public on October 9, 2000, and currently has more than 1000 items displayed in 45 themed display cases. A newly themed concept of Incremental Development of Eminent Anesthesia Landmarks to Operational Routine was developed for the display and explanation of the history of anesthesia related to pioneers, equipment, books, and manuscripts. A display concept combining Person, Publication, and Apparatus is used throughout the museum. A well-stocked library currently holds more than 13,000 books and periodicals. The museum's 10-year anniversary was celebrated with a symposium entitled "German Pioneers in Anaesthesia of the first 100 years," held at the University of Bonn on October 8, 2010. The museum's Web site in German, English, and French is www.anaesthesia-museum.uni-bonn.de.


The effects of heparin versus normal saline for maintenance of peripheral intravenous locks in pregnant women.
To compare the efficacy of two available preparations (heparin, 10 U/mL, 1 mL, vs. normal saline, 1 mL) used for maintaining patency in peripheral intravenous (IV) locks during pregnancy. Prospective, randomized, and double-blind. Eligible patients who were to receive a peripheral intermittent IV lock were randomly assigned to receive either heparin flushes or normal saline flushes for IV lock maintenance. IV locks were flushed after each medication administration, or at least every 24 hours, with the assigned blinded flush solution. Intermittent IV lock sites were also evaluated every 12 hours for the development of phlebitis. A large academic medical center in the Midwest that has both community-based and regional-referral obstetric practices with more than 2,000 deliveries per year. A convenience sample included 73 hospitalized pregnant women who were between 24 and 42 weeks gestation. Exclusions from the study were women with significant abnormalities in the fetal heart tracing on admission, cervical dilation > 4 cm, presence of hypersensitivity to heparin, presence of clotting abnormalities, and anticoagulation therapy (including low-dose aspirin). Data indicate there were no statistically significant differences in IV lock patency nor in phlebitis between heparin or normal saline flushes. This study provides support that both normal saline and heparin in the doses studied may be equally effective in the maintenance of peripheral IV locks. Due to small sample size, additional studies are needed to determine optimal therapy over time.


Differential epigenetic reprogramming in response to specific endocrine therapies promotes cholesterol biosynthesis and cellular invasion.
Endocrine therapies target the activation of the oestrogen receptor alpha (ERα) via distinct mechanisms, but it is not clear whether breast cancer cells can adapt to treatment using drug-specific mechanisms. Here we demonstrate that resistance emerges via drug-specific epigenetic reprogramming. Resistant cells display a spectrum of phenotypical changes with invasive phenotypes evolving in lines resistant to the aromatase inhibitor (AI). Orthogonal genomics analysis of reprogrammed regulatory regions identifies individual drug-induced epigenetic states involving large topologically associating domains (TADs) and the activation of super-enhancers. AI-resistant cells activate endogenous cholesterol biosynthesis (CB) through stable epigenetic activation in vitro and in vivo. Mechanistically, CB sparks the constitutive activation of oestrogen receptors alpha (ERα) in AI-resistant cells, partly via the biosynthesis of 27-hydroxycholesterol. By targeting CB using statins, ERα binding is reduced and cell invasion is prevented. Epigenomic-led stratification can predict resistance to AI in a subset of ERα-positive patients.


Peptide mediated formation of noble metal nanoparticles-controlling size and spatial arrangement.
Over the past two decades, peptides have expanded the toolbox of additives for the preparation of noble metal nanoparticles. Their functional and structural modularity and accompanying molecular recognition and self-assembly properties offer unique opportunities for the controlled formation of NPs. Within this review, we highlight recent examples for the use of peptides to control a) the size and shape of NPs and b) the spatial arrangement of NPs. The article focuses on examples where the peptides are directly involved in the bottom-up synthesis of the noble metal NPs.


Neurobehavioral changes in Taiwanese lead-exposed workers.
The dysfunction of the central nervous system (CNS) caused by lead exposure was evaluated. Workers who have been exposed to lead for at least 3 years and have been informed of having elevated blood lead levels (BLLs) were recruited. According to their current BLLs, 33 and 28 males were assigned to the medium (40-80 microg/dL) and low (<40 microg/dL) BLLs groups, respectively. Sixty-two nonexposed healthy men served as the control group. Their neurobehaviors were examined by a computerized evaluation system. Significantly impaired neurobehavioral functions were shown in the medium BLLs group, which included slow performance of psychomotor tasks, impaired processing of visual-spatial information, reduced memory and learning functions, low performance accuracy, slow execution of responses, and poor attentional control. Subtle CNS dysfunction could be detected from lead-exposed workers who have no obvious neurologic and cognitive deficits.


The 2022 Society for Vascular Surgery, American Venous Forum, and American Vein and Lymphatic Society clinical practice guidelines for the management of varicose veins of the lower extremities. Part I. Duplex Scanning and Treatment of Superficial Truncal Reflux: Endorsed by the Society for Vascular Medicine and the International Union of Phlebology.
The Society for Vascular Surgery, American Venous Forum, and American Vein and Lymphatic Society collaborated to update the 2011 Society for Vascular Surgery/American Venous Forum clinical practice guidelines and provide new evidence-based recommendations on critical issues affecting the care of patients with varicose veins. Each recommendation is based on a recent, independent systematic review and meta-analysis of the diagnostic tests and treatments options for patients with lower extremity varicose veins. Part I of the guidelines includes evidence-based recommendations for the evaluation of patients with CEAP (Clinical Class, Etiology, Anatomy, Pathology) class 2 varicose vein using duplex ultrasound scanning and other diagnostic tests, open surgical treatment (ligation and stripping) vs endovenous ablation techniques, thermal vs nonthermal ablation of the superficial truncal veins, and management of incompetent perforating veins in CEAP class 2 disease. We have also made recommendations on the concomitant vs staged treatment of varicose tributaries using phlebectomy or liquid or foam sclerotherapy (with physician-compounded foam or commercially prepared polidocanol endovenous microfoam) for patients undergoing ablation of incompetent superficial truncal veins.


Quantification of Nanoscale Dose Enhancement in Gold Nanoparticle-Aided External Photon Beam Radiotherapy.
The recent progress in Nanotechnology has introduced Gold Nanoparticles (AuNPs) as promising radiosensitizing agents in radiation oncology. This work aims to estimate dose enhancement due to the presence of AuNPs inside an irradiated water region through Monte Carlo calculations. The GATE platform was used to simulate 6 MV photon histories generated from a TrueBeam® linear accelerator with and without a Flattening Filter (FF) and model AuNPs clusters. The AuNPs size, concentration and distribution pattern were examined. To investigate different clinical irradiation conditions, the effect of field size, presence of FF and placement of AuNPs in water were evaluated. The range of Dose Enhancement Factors (DEF = DoseAu/DoseWater) calculated in this study is 0.99 ± 0.01-1.26 ± 0.02 depending on photon beam quality, distance from AuNPs surface, AuNPs size and concentration and pattern of distribution. The highest DEF is reported for irradiation using un-flattened photon beams and at close distances from AuNPs. The obtained findings suggest that dose deposition could be increased in regions that represent whole cells or subcellular targets (mitochondria, cell nucleus, etc.). Nevertheless, further and consistent research is needed in order to make a step toward AuNP-aided radiotherapy in clinical practice.