Influence of FcgammaRIIA and MBL polymorphisms on severe acute respiratory syndrome.
Polymorphisms of human Fc gamma-receptor IIA (FcgammaRIIA) and mannose-binding lectin (MBL) genes have been associated with susceptibility to or severity of some infectious diseases. In order to investigate whether these genetic factors might influence susceptibility to infection with the severe acute respiratory syndrome-associated coronavirus (SARS-Cov) as well as the course and severity of the infection, we evaluated polymorphisms of FcgammaRIIA and MBL genes in DNA samples from a group of approximately 180 people from Hong Kong who were infected with SARS-Cov. These included 132 patients who had moderate course of SARS infection (home subgroup), 26 patients with a severe course requiring treatment in an intensive care ward (ICU subgroup) and a subgroup of 22 patients who died from SARS (deceased subgroup). A total of 200 normal blood donors from the same region were used as controls. A significant association was found between the FcgammaRIIA-R/R131 genotype and a severe course of SARS, with higher frequency of homozygosity for FcgammaRIIA-R/R131 in the ICU subgroup of SARS patients when compared with controls (P=0.03; odds ratio: 3.2; 95% confidence interval: 1.1-9.1). In comparison with controls, a significant difference in linear trend distribution of FcgammaRIIA genotypes was seen among the severe SARS patients (ICU and deceased subgroups) without co-morbidity, and the incidence of FcgammaRIIA-H/H131 was lower in these patients as well. There were no significant differences in MBL genotypes and allele frequencies among SARS patients and controls. The study reveals that in addition to age and co-morbidity, FcgammaRIIA polymorphism of individuals may also influence outcome after infection with the SARS-Cov.


A comprehensive assessment of long intrinsic protein disorder from the DisProt database.
Intrinsic disorder (ID), i.e. the lack of a unique folded conformation at physiological conditions, is a common feature for many proteins, which requires specialized biochemical experiments that are not high-throughput. Missing X-ray residues from the PDB have been widely used as a proxy for ID when developing computational methods. This may lead to a systematic bias, where predictors deviate from biologically relevant ID. Large benchmarking sets on experimentally validated ID are scarce. Recently, the DisProt database has been renewed and expanded to include manually curated ID annotations for several hundred new proteins. This provides a large benchmark set which has not yet been used for training ID predictors. Here, we describe the first systematic benchmarking of ID predictors on the new DisProt dataset. In contrast to previous assessments based on missing X-ray data, this dataset contains mostly long ID regions and a significant amount of fully ID proteins. The benchmarking shows that ID predictors work quite well on the new dataset, especially for long ID segments. However, a large fraction of ID still goes virtually undetected and the ranking of methods is different than for PDB data. In particular, many predictors appear to confound ID and regions outside X-ray structures. This suggests that the ID prediction methods capture different flavors of disorder and can benefit from highly accurate curated examples. The raw data used for the evaluation are available from URL: http://www.disprot.org/assessment/. email@example.com. Supplementary data are available at Bioinformatics online.


Osteoporosis in older men.
Historically, the focus in osteoporosis has been on postmenopausal women. In the past few years, information about osteoporosis in other populations, including men, has begun to emerge. Although less common in older men, osteoporosis nonetheless represents a major health concern. Approximately 30% of hip fractures worldwide occur in men, resulting in significant mortality and loss of independence. The incidence of osteoporotic fractures in men is increasing. The reason for this is unclear, but improvement in longevity and better management of other chronic diseases most likely play a role. Two recent studies have addressed the question of fracture risk in men past middle age and have estimated that men > 50 years of age have a 19% to 25% lifelong risk of osteoporotic fracture. Mortality is higher following hip fracture and pain is more intense in men than in women following severe vertebral fracture.


The correlation of cold agglutinin titrations in saline and albumin with haemolytic anaemia.
Cold agglutinin syndrome (CAS) is usually associated with IgM cold agglutinins with titres exceeding 1000 at 4 degrees C and a thermal amplitude of 30-32 degrees C. Occasionally patients are encountered who although having clinical and laboratory findings compatible with CAS do not have the characteristic serological findings. Thirty-two patients with a positive direct antiglobulin test due to complement sensitization were studied. Thirty-one of these patients had cold agglutinin titres greater than 64. Twenty-eight had haemolytic anaemia, including one patient with a cold agglutinin titre of only 8 against saline-suspended red cells. 53.6% of sera from patients with haemolytic anaemia reacted at 30 degrees C and 7.1% at 37 degrees C when albumin was not present, whereas in the presence of albumin all of the sera reacted at 30 degrees C and 67.9% reacted at 37 degrees C. None of the four patients without haemolytic anaemia reacted at 30 degrees C or 37 degrees C in the presence of albumin, even though one serum reacted to a titre of 1280 at 4 degrees C. Cold agglutinin titres and thermal amplitudes in the presence of bovine albumin were found to correlate better with haemolytic anaemia than reactions without albumin. If bovine albumin is utilized in compatibility testing, multiple cold autoabsorptions may be necessary before alloantibody activity at 37 degrees C can be excluded.


Development of a C18 Supercritical Fluid Chromatography-Tandem Mass Spectrometry Methodology for the Analysis of Very-Long-Chain Polyunsaturated Fatty Acid Lipid Matrices and Its Application to Fish Oil Substitutes Derived from Genetically Modified Oilseeds in the Aquaculture Sector.
Lipidomics methodologies traditionally utilize either reverse phase- or hydrophilic interaction liquid chromatography-type separations; however, supercritical fluid chromatography can offer a rapid normal phase type separation while reducing the dependence on organic solvents. However, normal phase type lipid separations typically lack pronounced intraclass separation, which is problematic for complex lipidomes containing very-long-chain polyunsaturated fatty acids, especially those from genetically modified organisms. A high-strength silica C18 method was developed, which benefitted from discrete class separation, as well as displaying intraclass selectivity sufficient for profiling flesh of salmon fed with a diet supplemented with oil from the genetically engineered oilseed Camelina sativa, a terrestrial oilseed with a fish oil-type profile. Salmon fed a diet containing this Camelina oil were found to have flesh enriched in triacylglycerols and phospholipids containing 18:3, 20:5, and 22:6, whereas salmon fed the control diet were differentiated by shorter chain plant-type fatty acids integrated within complex lipids. Coupled with active scanning quadrupole technology, data acquisition was enhanced, allowing for fragmentation data to be acquired in a data independent fashion, permitting acyl chain identification of resolved isomers. Therefore, we have developed a method, which is amenable for lipidomics studies of complex lipidomes, specifically those altered by synthetic biology approaches.


Inhibitory effects of ATP and other nucleotides on atrial natriuretic peptide (ANP) binding to R1-type ANP receptors in human neuroblastoma NB-OK-1 cell membranes.
ATP dose-dependently inhibited rat 125I-ANP-(99-126) binding to membranes from the human neuroblastoma cell line NB-OK-1 by increasing the KD value for the hormone without altering the Bmax value. After a 20 min preincubation with 37.5 pM 125I-ANP-(99-126) and 0.5 mM ATP, followed by the addition of 0.3 microM unlabelled ANP-(99-126), the proportion of rapidly dissociating receptors was 4-times higher than in the absence of ATP. The other nucleotides ADP, AMP, AMP-PNP, ATP gamma S, GTP, GDP, GMP, GMP-PNP and GTP gamma S were also inhibitory but with a lower potency and/or efficacy. Binding equilibrium data were satisfactorily simulated by a computer program based on partially competitive binding of ANP-(99-126) and the nucleotides, and this, together with the data on dissociation kinetics, strongly suggests that several nucleotides, when added at concentrations up to 1 mM, form a ternary ANP-receptor-nucleotide complex.


Nedocromil sodium vs. sodium cromoglycate pressurized aerosol in the prevention of bronchoconstriction induced by ultrasonic nebulized distilled water in asthmatic children.
To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate (SCG), administered by metered dose inhaler (MDI) with a 700 mL holding chamber (Fisonair Fisons UK) in preventing bronchoconstriction induced by inhalation of ultrasonically nebulized distilled water (UNDW), 12 asthmatic children were studied in a randomized, double-blind, placebo-controlled, intrapatient study. Following a baseline challenge with UNDW, the protective effect of NS, SCG, or placebo was evaluated in each subject. Cumulative doses of delivered nebulized water producing a 20% fall in forced expiratory volume in 1 sec (PD20 UNDW) was measured. Mean (+/- SD) PD20 UNDW was 4.83 (+/- 4.84), 10.16 (+/- 7.05), 1.58 (+/- 0.5), and 15.93 (+/- 0.23) respectively, for baseline, and placebo, SCG, and NS-treated groups. A significant (P < 0.05) protection from UNDW induced bronchoconstriction by NS was observed in comparison with placebo, while no such effect was evident when the children were treated with SCG.


Efficacy of sucralfate and cimetidine in protection of the human gastric mucosa against alcohol injury.
In order to study whether sucralfate or cimetidine may protect human gastric mucosa against alcohol injury, 28 healthy volunteers were pretreated with either: (1) placebo 1 g; (2) cimetidine (Tagamet) 300 mg; or (3) sucralfate (Carafate) 1 g. One hour later, 100 ml of 40 percent ethanol was sprayed directly on the gastric mucosa of the greater curvature during an endoscopic examination. Gastric mucosal changes were assessed by endoscopic appearance (according to grading scale) and by histology. In placebo-pretreated subjects, alcohol produced prominent mucosal damage (endoscopic score, 3.9 +/- 0.3, histologic score, 4.0 +/- 1.1 at 30 minutes). Cimetidine alkalinized gastric pH but did not prevent alcohol-induced damage (endoscopic score, 4.0 +/- 0.6; histologic score, 3.8 +/- 1.1, at 30 minutes). Sucralfate reduced endoscopic and histologic features of alcohol injury (endoscopic score, 1.8 +/- 0.6; histologic score, 1.8 +/- 1.1, at 30 minutes) without affecting gastric luminal pH. Reduction of alcohol-induced injury of the human gastric mucosa by sucralfate but not cimetidine demonstrates that effective protection of the gastric mucosa can be achieved without neutralization or inhibition of gastric acid secretion and points out another clinical application for sucralfate.


Superstrong Carbon Nanotube Yarns by Developing Multiscale Bundle Structures on the Direct Spin-Line without Post-Treatment.
Super strong fibers, such as carbon or aramid fibers, have long been used as effective fillers for advanced composites. In this study, the highest tensile strength of 5.5 N tex-1 for carbon nanotube yarns (CNTYs) is achieved by controlling the micro-textural structure through a facile and eco-friendly bundle engineering process in direct spinning without any post-treatment. Inspired by the strengthening mechanism of the hierarchical fibrillary structure of natural cellulose fiber, this study develops multiscale bundle structures in CNTYs whereby secondary bundles, ≈200 nm in thickness, evolve from the assembly of elementary bundles, 30 nm in thickness, without any damage, which is a basic load-bearing element in CNTY. The excellent mechanical performance of these CNTYs makes them promising substitutes for the benchmark, lightweight, and super strong commercial fibers used for energy-saving structural materials. These findings address how the tensile strength of CNTY can be improved without additional post-treatment in the spinning process if the development of the aforementioned secondary bundles and the corresponding orientations are properly engineered.


High-density lipoproteins attenuate high glucose-impaired endothelial cell signaling and functions: potential implications for improved vascular repair in diabetes.
Abnormalities of endothelial cell function are proposed to be a critical factor underlying adverse cardiovascular outcomes in the setting of hyperglycaemia. While high-density lipoproteins (HDL) have been demonstrated to be cardioprotective, the impact on the endothelium in hyperglycaemia has not been fully elucidated. Human umbilical vein endothelial cells (HUVECs) were exposed to high-glucose conditions using dextrose, the main isoform of glucose, and native HDL. HUVEC proliferation and migration were determined. The key signalling pathways that regulate endothelial cell function were also characterized. Increasing concentrations of dextrose resulted in significant reductions in HUVEC proliferation, this was attenuated by coincubation with HDL. In support of this, HDL was also found to rescue dextrose impaired expression of PCNA and the activation (phosphorylation) of the key transcription factor for proliferation ERK. Dextrose also dose-dependently inhibited HUVEC migration, which was mitigated by co-incubation with HDL. Consistent with this, HDL prevented dextrose-induced inhibition of p38 phosphorylation, responsible for cell migration. Finally, phosphorylation of the pro-survival transcription factor Akt was dose-dependently inhibited by dextrose, however, this was completely rescued by co-administration with HDL. Dextrose-induced hyperglycaemia causes the impairment of endothelial cell proliferation and migration and inhibits the activation of ERK, p38 and Akt pathways. The protective effects of HDL in this milieu highlights the potential for HDL to improve vascular repair in patients with impaired glucose homeostasis.


Cytopathological differential diagnosis of malignant tumor cells in the cerebrospinal fluid: A retrospective analysis.
Leptomeningeal metastasis is the spread of cancer to the leptomeninges and subarachnoid space and represents a dreadful complication of cancer. The most commonly responsible neoplasms are high-grade lymphomas, leukemias, and some solid tumors, chiefly breast and lung cancer as well as melanoma. Herein we report our ten-year retrospective experience on 715 cases of cerebrospinal fluid cytology, 21 (2.9%) of which were positive for leptomeningeal metastasis. Sample collection and processing, clinical history, interdisciplinary dialog, and ancillary techniques such as immunocytochemistry and flow cytometry are all fundamental in reaching the correct diagnosis and thus optimally caring for patients with leptomeningeal metastasis.


Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha.
Repression of gene transcription by nuclear receptors is mediated by interactions with co-repressor proteins such as SMRT and N-CoR, which in turn recruit histone deacetylases to the chromatin. Aberrant interactions between nuclear receptors and co-repressors contribute towards acute promyelocytic leukaemia and thyroid hormone resistance syndrome. The binding of co-repressors to nuclear receptors occurs in the unliganded state, and can be stabilized by antagonists. Here we report the crystal structure of a ternary complex containing the peroxisome proliferator-activated receptor-alpha ligand-binding domain bound to the antagonist GW6471 and a SMRT co-repressor motif. In this structure, the co-repressor motif adopts a three-turn alpha-helix that prevents the carboxy-terminal activation helix (AF-2) of the receptor from assuming the active conformation. Binding of the co-repressor motif is further reinforced by the antagonist, which blocks the AF-2 helix from adopting the active position. Biochemical analyses and structure-based mutagenesis indicate that this mode of co-repressor binding is highly conserved across nuclear receptors.


[Epidemiological surveys of formaldehyde and nitrogen dioxide levels in indoor air].
The influence of HCHO and NO2 on clinical, haematological, immunological, sensory and lung function parameters were tested in 129 children out of 3 classes. As part of a biological monitoring programme formic acid content in urine was determined. Concentration of the pollutants in indoor air was measured by means of passive samples.


Alteration of adenine nucleotide pool in old rat liver and its normalization with ammonium succinate.
Ammonium succinate administration into the old rats increases the sum of adenine nucleotide and normalizes all indices of adenine nucleotide metabolism in the liver to the levels typical for the intact young animals.


The potential role of resistin in atherogenesis.
Resistin, an adipocyte-derived cytokine linked to insulin resistance and obesity, has recently been shown to activate endothelial cells (ECs). Using microarrays, we found that along with numerous other pro-atherosclerotic genes, resistin expression levels are elevated in the aortas of C57BL/6J apoE-/- mice; these findings led us to further explore the relation between resistin and atherosclerosis. Using TaqMan PCR and immunohistochemistry, we found that ApoE-/- mice had significantly higher resistin mRNA and protein levels in their aortas, and elevated serum resistin levels, compared to C57BL/6J wild-type mice. Incubation of murine aortic ECs with recombinant resistin increased monocyte chemoattractant protein (MCP)-1 and soluble vascular cell adhesion molecule (sVCAM)-1 protein levels in the conditioned medium. Furthermore, human carotid endarterectomy samples stained positive for resistin protein, while internal mammary artery did not show strong staining. Patients diagnosed with premature coronary artery disease (PCAD) were found to have higher serum levels of resistin than normal controls. In summary, resistin protein is present in both murine and human atherosclerotic lesions, and mRNA levels progressively increase in the aortas of mice developing atherosclerosis. Resistin induces increases in MCP-1 and sVCAM-1 expression in murine vascular endothelial cells, suggesting a possible mechanism by which resistin might contribute to atherogenesis. Finally, PCAD patients exhibited increased serum levels of resistin when compared to controls. These findings suggest a possible role of resistin in cardiovascular disease.


A Six-Year Follow-up of People Who Use Cannabis in Iran - A Case Series.
Frequent cannabis use is associated with adverse health-related outcomes. This study followed up individuals who used cannabis to assess their use and adverse event status. The eligible individuals, recruited in the Iranian Mental Health Survey (IranMHS), were contacted via telephone calls six years after the index interview. The frequency of cannabis use and the occurrence of selected adverse events were recorded. The baseline status was extracted from the index survey. If any individual was inaccessible, his/her vital status was assessed. Of the 50 eligible individuals (all male), two had died. Moreover, from among 25 reached participants, 19 reported abstinence from cannabis in the past year, and 18 reported at least one adverse event in the past six years. Violence and imprisonment were the most common events reported. Six years after the index interview, most of the participants abstained from cannabis. Besides, adverse events were common, emphasizing the need for further investigations on larger samples of cannabis users.


Mutagenic activation of dialkylnitrosamines by intact urothelial cells.
Intact urothelial cells isolated from bladders of untreated inbred NZO/BIGd or NZC/BIGd mice and NZR/Gd rats activated dimethyl, diethyl, dipropyl, and dibutyl nitrosamines in a liquid culture mutagenesis fluctuation assay using Salmonella typhimurium TA100 as target organism. Rat and mouse urothelial cells were highly effective at 1.5 X 10(5) cells/ml, in O2 gas phase, and no cofactors were required. Relative mutagenic activities were estimated at equitoxic (LD50) concentrations of the 4 nitrosamines. Nitrosamines with odd-carbon chain substitutents were more active than the C-even compounds. Although dibutylnitrosamine is a powerful bladder carcinogen in both rats and mice while the other 3 compounds very rarely cause bladder tumours, the most active promutagens were dipropyl and dimethyl, followed by diethyl and dibutyl nitrosamines. None were active in absence of urothelial cells. Mouse bladder cells were more active than those from NZR rats. There were sex differences in the mice with NZC males and NZO females predominating, but in NZR rats urothelial cells from male and female animals were equally active. These dialkylnitrosamines are widely distributed in the environment, and our results indicate that direct mutagenic activation in the urothelium could be one factor contributing to the incidence of bladder cancer.


Allergenic activity of an air-oxidized ethoxylated surfactant.
Ethoxylated surfactants are used in household and industrial cleaners, topical pharmaceuticals, cosmetics and laundry products. Polyethers, e.g. ethoxylated surfactants and polyethylene glycols, are oxidized by atmospheric oxygen (autoxidized) when stored and handled. We have previously shown that a chemically well-defined non-ionic surfactant, the ethoxylated alcohol penta-ethylene glycol mono-n-dodecyl ether (C12E5), forms a complex mixture of autoxidation products when exposed to air. Predictive testing in guinea pigs showed that the surfactant itself is a non-sensitizer, but that oxidation products formed are skin sensitizers. The aim of this study was to investigate the sensitizing capacity of a total oxidation mixture of C12E5 obtained after autoxidation. The allergenic activity of different oxidation products is discussed as well as the clinical importance of the findings. This study shows that the non-ionic surfactant C12E5 containing 20% oxidation products is a sensitizing mixture. The result accords with what is observed for other compounds that are unstable when in contact with air, e.g. limonene and linalool, major fragrance terpenes. Studies regarding the clinical relevance of our findings should be performed. However, it is already clear from this study that precautions must be taken in handling and storage of ethoxylated surfactants to avoid formation of allergenic mixtures.


CDK4/6 Inhibitor Biomarker Research: Are We Barking Up the Wrong Tree?
CDK4/6 inhibitors have emerged as a significant advance for the treatment of patients with advanced estrogen receptor-positive breast cancer. However, the identification of predictive markers that optimize their use is proving harder than expected. In this commentary we advocate for unbiased discovery and a collaborative approach across trials.See related article by Finn et al., p. 110.


Eradication rate of Helicobacter pylori reinfection in Korea: A retrospective study.
Guidelines for selecting the eradication regimen for Helicobacter pylori reinfection remain unclear. This study aimed to evaluate the eradication rate of H. pylori reinfection in patients with a previous infection successfully eradicated with index triple therapy. This was a single-center, retrospective case-control study. A total of 10 468 H. pylori-infected patients treated with proton-pump inhibitor-based triple eradication therapy at a tertiary medical institution between 2005 and 2016 were enrolled. We reviewed the medical records of the enrolled patients and compared the treatment outcomes in those with H. pylori reinfection after a successful eradication. Helicobacter pylori infection was successfully eradicated with the index triple therapy in 7770 patients (74.2%). Among 3567 patients followed up for > 1 year, H. pylori reinfection occurred in 420 (11.8%; 3.06% per person-year) during a median follow-up of 39.1 months (interquartile range, 23.5-58.7 months). Of these patients, 164 received eradication therapy for reinfection (triple therapy in 102 and quadruple therapy in 62) and had follow-up data. Triple therapy showed an eradication rate of 78.4% for H. pylori reinfection, which was not significantly different from that of the index triple therapy (P = 0.394). Quadruple therapy for reinfection exhibited a better eradication rate (87.1%) than triple therapy but without statistical significance (P = 0.237). Retreatment with triple therapy for H. pylori reinfection after successful eradication of prior infection showed comparable outcomes to the index triple therapy. Bismuth-containing quadruple therapy for reinfection tended to have a better eradication rate than did triple therapy.


Spinal mechanisms of the functional stretch reflex.
A sudden and rapid angular displacement of the limb evokes, in human and monkey subjects, a segmented pattern of electromyographic activity in muscles which are stretched. While the first segment is acknowledged to represent a tendon jerk, it has been proposed that the second segment, occurring with a shorter latency than a reaction time, is mediated by a transcortical loop. The present experiments were conducted in cats to determine the properties of muscle responses to torque perturbations analogous to those used in the monkey, and to determine if the integrity of supraspinal pathways is required for the individual response segments to occur. Torque perturbations which flexed the forearm evoked a segmented response in the electromyogram of the cat triceps muscle. This response typically consisted of three early segments with latencies of 10, 30 and 60 msec which were similar to the M1, M2, and M3 segments described in the monkey. The M3 and occasionally M2 components were depressed when the cat followed rather than resisted the perturbation. A torque pulse of 10 msec duration was sufficient to elicit a near maximal M1 response while torque pulses in excess of 20 msec were required to evoke the M2 response. To determine if any of these components required mediation by the cerebral cortex, experiments were conducted in decerebrate and spinal cats. Similar torque perturbations produced segmented electromyographic responses in the triceps muscles which were indistinguishable in their timing from those observed in intact cats. The torque required to produce the segmented responses was comparable as well. All three segments were dependent upon the activation of receptors in the homonymous muscle and did not require cutaneous input. These observations show that receptor properties and/or spinal mechanisms involved in the stretch reflex are sufficient to produce a segmented response similar to that observed in intact animals.


Infections in surgery of primary tumors of the sacrum.
Retrospective case series. To evaluate the risk of infection, related treatment, and outcome after surgery of the 2 most common primary sacral tumors. Rarity of sacral tumors has limited the number of population-based studies. Treatment depends on malignancy or local aggressiveness: wide resection is indicated for malignant lesions, intralesional surgery for benign. We studied 82 patients with sacral chordomas (55 cases) or giant cell tumor (GCT) (27 cases) treated between 1976 and 2005. All patients had IV antibiotic therapy with amikacin and teicoplanin. Surgery of chordoma was resection; surgery of GCT was intralesional excision. Infections were classified as immediate postoperative, early (within 6 months), and late (more than 6 months from surgery). Mean follow-up was 9.5 years (range: 3-27 years). Some factors possibly influencing the risk of infection were statistically analyzed by Kaplan Meier curves and log-rank test. No deep infections were observed in the GCT series. Three patients with sacral chordoma died for postoperative complications and were excluded from this analysis. Of the remaining 52 patients with chordoma, 23/52 had deep wound infection (44%) that required 1 or more surgical debridements combined with antibiotics, according to cultures. In 16 patients (70%), infection occurred within 4 weeks postoperatively, and in 7 within 6 months. Most frequent bacteria were Enterococcus (23%), Escherichia coli (20%), and Pseudomonas aeruginosa (18%). In 74% of cases, infection was multimicrobial. Level of resection, previous intralesional treatment elsewhere, tumor volume, and age did not statistically influence risk of infection. Type of surgery was the prominent factor related to a major risk of infection. Operating procedure time correlated as well. Resections of sacral chordoma imply a high risk of deep infection, while intralesional excision of GCT does not. All infections healed with surgical debridements and antibiotic therapy.


Rhamnolipid production by Pseudomonas aeruginosa immobilised in polyvinyl alcohol beads.
A marine bacterium, Pseudomonas aeruginosa BYK-2 (KCTC 18012P), was immobilised by entrapment in 10% (w/v) polyvinyl alcohol beads and optimized for the continuous production of rhamnolipid. The relative activity of rhamnolipid production was maintained at 80 approximately 90% of the initial production during 15 cycles in a repeated batch culture. Continuous culture was performed in a 1.8 1 airlift bioreactor, yielding 0.1 g rhamnolipid h(-1) at a dilution rate of 0.0 18 h(-1), 25 degrees C, initial pH 7, and 0.5 vvm aeration rate with a 1.21 working volume.


Outcomes of Consolidative Nephrectomy following Primary Immunotherapy in Advanced Renal Cell Carcinoma: A Multicenter Analysis.
To evaluate effect and outcomes of combination primary immunotherapy (IO) and nephrectomy for advanced renal cell carcinoma (RCC). We conducted a multicenter, retrospective analysis of patients with advanced/metastatic RCC who received IO followed by nephrectomy. Primary outcome was Bifecta (negative surgical margins and no 30-day surgical complications). Secondary outcomes included progression-free survival (PFS) following surgery, reduction in tumor/thrombus size, RENAL score, and clinical/pathologic downstaging. Cox regression multivariable analysis was conducted for predictors of Bifecta and PFS. Kaplan-Meier analysis assessed PFS, comparing Bifecta and non-Bifecta groups. A total of 56 patients were analyzed (median age 63 years; median follow-up 22.5 months). A total of 40 (71.4%) patients were intermediate IMDC risk. Patients were treated with immunotherapy for median duration of 8.1 months. Immunotherapy resulted in reductions in tumor size (P < .001), thrombus size (P = .02), and RENAL score (P < .001); 38 (67.9%) patients were clinically downstaged on imaging (P < .001) and 25 (44.6%) patients were pathologically downstaged following surgery (P < .001). Bifecta was achieved in 38 (67.9%) patients. Predictors for bifecta achievement included decreasing tumor size (HR 1.08, P = .043) and pathological downstaging (HR 2.13, P = .047). Bifecta (HR 5.65, P = .009), pathologic downstaging (HR 5.15, P = .02), and increasing reduction in tumor size (HR 1.2, P = .007) were associated with improved PFS. Bifecta patients demonstrated improved 2-year PFS (84% vs. 71%, P = .019). Primary immunotherapy reduced tumor/thrombus size and complexity. Pathologically downstaged patients were more likely to achieve bifecta, and these patients displayed improved 2-year PFS. Our study supports further inquiry in the use of CRN following primary immunotherapy for advanced renal cancer.


Cobalt-catalyzed hydrogen desorption from the LiNH2-LiBH4 system.
A doping of 5 wt% CoCl2 considerably decreases the dehydrogenation temperature of a mixture of LiNH2 and LiBH4. More that 8 wt% of hydrogen can be released at ca. 155 degrees C. X-Ray absorption near edge structure (XANES) spectroscopy indicated the formation of metallic Co after ball milling CoCl2 with LiNH2 and LiBH4. Extended X-ray absorption fine structure (EXAFS) spectroscopy measurements revealed that Co particles have poor crystallinity and are finely dispersed in the sample, which could lead to a high catalytic efficiency.


Specific Intensity for Peaking: Is Race Pace the Best Option?
The peaking period for endurance competition is characterized for a relative increase of the intensity of training, after a longer period of training relatively dominated by lower intensity and higher volume. The present study was designed to compare physiological and 10 km performance effects of high intensity training (HIT) versus race pace interval training (RP) during peaking for competition in well-trained runners. 13 athletes took part in the study, they were divided into two groups: HIT and RP. HIT performed short intervals at ~105% of the maximal aerobic velocity (MAV), while RP trained longer intervals at a speed of ~90% of the MAV (a speed approximating 10 km race pace). After 12 weeks of baseline training, the athletes trained for 6 weeks under one of the two peaking regimes. Subjects performed 10 km prior to and after the intervention period. The total load of training was matched between groups during the treatment phase. Subjects completed a graded treadmill running test until volitional exhaustion prior to each 10 km race. MAV was determined as the minimal velocity eliciting maximal oxygen consumption (VO2max). Both groups significantly improved their 10 km time (35 minutes 29 seconds ± 1 minutes 41 seconds vs 34 minutes 53 seconds ± 1 minutes 55 seconds, P < 0.01 for HIT; 35 minutes 27 seconds ± 1 minutes 40 seconds vs 34 minutes 53 seconds ± 1 minutes 18 seconds P < 0.01 for RP). VO2max increased after HIT (69 ± 3.6 vs 71.5 ± 4.2 ml.Kg(-1).min(-1), P < 0.05); while it didn't for RP (68.4 ± 6 vs 69.8 ± 3 ml.Kg(-1).min(-1), p>0.05). In contrast, running economy decreased significantly after HIT (210 ± 6 ml.Kg(-1).km(-1) vs 218 ± 9, P < 0.05). A 6 week period of training at either 105% of MAV or 90% of MAV yielded similar performance gains in a 10km race performed at ~90% MAV. Therefore, the physiological impact of HIT training seems to be positive for VO2max but negative for running economy.


Captive Breeding and Trichomonas gallinae Alter the Oral Microbiome of Bonelli's Eagle Chicks.
Bonelli's eagle (Aquila fasciata) is an endangered raptor species in Europe, and trichomonosis is one of the menaces affecting chicks at nest. In this paper, we attempt to describe the oral microbiome of Bonelli's eagle nestlings and evaluate the influence of several factors, such as captivity breeding, Trichomonas gallinae infection, and the presence of lesions at the oropharynx. The core oral microbiome of Bonelli's eagle is composed of Firmicutes, Bacteroidota, Fusobacteria and Proteobacteria as the most abundant phyla, and Megamonas and Bacteroides as the most abundant genera. None of the factors analysed showed a significant influence on alfa diversity, but beta diversity was affected for some of them. Captivity breeding exerted a high influence on the composition of the oral microbiome, with significant differences in the four most abundant phyla, with a relative increase of Proteobacteria and a decrease of the other three phyla in comparison with chicks bred at nest. Some genera were more abundant in captivity bred chicks, such as Escherichia-Shigella, Enterococcus, Lactobacillus, Corynebacterium, Clostridium and Staphylococcus, while Bacteroides, Oceanivirga, Peptostreptococcus, Gemella, Veillonella, Mycoplasma, Suttonella, Alloscardovia, Varibaculum and Campylobacter were more abundant in nest raised chicks. T. gallinae infection slightly influenced the composition of the microbiome, but chicks displaying trichomonosis lesions had a higher relative abundance of Bacteroides and Gemella, being the last one an opportunistic pathogen of abscess complications in humans. Raptor's microbiomes are scarcely studied. This is the first study on the factors that influence the oral microbiome of Bonelli's eagle.


Immunohistochemical localization of corticotropin-releasing factor (CRF)-containing neurons in the hypothalamus of the Japanese quail, Coturnix coturnix.
Immunohistochemical localization of corticotropin-releasing factor (CRF)-like immunoreactivity in the brain of the Japanese quail was studied by means of the peroxidase anti-peroxidase (PAP) method. CRF-immunopositive perikarya of parvocellular neurons were observed mainly in the nucleus praeopticus medialis and nucleus paraventricularis. Additional perikarya were also detected in the nucleus hypothalamicus posterior medialis in the hypothalamus and in the non-hypothalamic nucleus accumbens, nucleus septalis lateralis and nucleus dorsomedialis and dorsolateralis thalami. No CRF immunoreaction was found to coexist with the vasotocin (Vt)-containing system in comparative examination of consecutive sections treated with anti-vasopressin (Vp) serum. The CRF-immunoreactive fibers were detected mainly in the external layer of the anterior median eminence but not in its posterior division. Unilateral adrenalectomy induced the marked reduction in number of the CRF immunopositive fibers in the anterior median eminence.


Draft Genome Sequence of a Mycobacterium Strain Isolated from a Clinical Wound Sample.
We report the draft genome sequence of an unusual Mycobacterium isolate recovered from a patient's arm tissue. The 4,025,753-bp draft genome exhibits a GC content of 71.02%, and a 16S rRNA gene analysis found that the closest relative was Mycobacterium grossiae.


Impact of the COVID-19 Pandemic on Ophthalmology Residency Training in Portugal.
The purpose of this study was to provide objective and real-life data concerning the impact of the COVID-19 pandemicon ophthalmology residency training in Portugal. Descriptive survey-based study applied to current Portuguese ophthalmology residents (n = 80 eligible). Seventy-five residents participated (94% response rate). All except one (99%) admitted a change in their routine clinical practice during the pandemic, and most (89%) continued to be engaged in ophthalmology department duties. Twenty-five percent were deployed to COVID-19 units, which was combined with ophthalmological activities in about half of them (47%). A significant proportion of participants stated that they were enrolled in the following ophthalmological activities: emergency/inpatient care (87%), outpatient visits (73%; general 70% vs subspecialty 29%), and surgical procedures (64%). Twenty-five percent did not assist in any outpatient visits and 36% did not participate in any surgical procedures. On a scale from 1 (no impact) to 5 (maximum impact), most participants classified their perceived negative impact of the pandemic on the training program as 3 (24%), 4 (40%), or 5 (27%). Participants highly agreed with the extension of the residency program (80%) in order to to make up for training disruption. Most trainees provided ophthalmological care during the pandemic. However, those clinical activities were essentially related to general and emergency care. Surgical experience was significantly curtailed. As such, strategies are needed to guarantee a high-quality learning process. Further studies are required to develop an international perspective on how ophthalmology training programs have been affected so that educational organizations can make recommendations regarding standardized adjustments to training programs. The COVID-19 pandemic has significantly impacted the training of ophthalmology residents nationwide.


RETINAL DEPOSITS OF TRIAMCINOLONE-MOXIFLOXACIN AFTER DROPLESS CATARACT SURGERY.
To report a case of epiretinal crystalline deposits observed on fundus examination and optical coherence tomography 2 years after transzonular intravitreal injection of triamcinolone-moxifloxacin (TriMoxi) during "dropless" cataract surgery. Observational case report with literature review of toxic effects of intravitreal triamcinolone and differential diagnosis of retinal crystalline deposits. A 37-year-old asymptomatic pseudophakic man presented with refractile crystalline retinal deposits that had prompted an extensive systemic embolic workup. The systemic evaluation for emboli was negative. OCT imaging revealed that the crystalline deposits were confined to the anterior surface of the internal limiting membrane. Further historical inquiry determined that transzonular intravitreal triamcinolone-moxifloxacin injection had been performed at the time of cataract surgery 2 years earlier. Transzonular triamcinolone acetonide delivered during cataract surgery can deposit on the retinal surface for long periods. These epiretinal crystalline deposits are benign and generally do not interfere with visual acuity. Nevertheless, clinicians should be aware of this differential diagnosis because clinical misdiagnosis can lead to unwarranted evaluation and treatment.


Ex-vivo assessment and non-invasive in vivo imaging of internal hemorrhages in Aga2/+ mutant mice.
Mutations in type I collagen genes (COL1A1/2) typically lead to Osteogenesis imperfecta, the most common heritable cause of skeletal fractures and bone deformation in humans. Heterozygous Col1a1(Aga2/+), animals with a dominant mutation in the terminal C-propeptide domain of type I collagen develop typical skeletal hallmarks and internal hemorrhages starting from 6 day after birth. The disease progression for Aga2/+ mice, however, is not uniform differing between severe phenotype lethal at the 6-11th day of life, and moderate-to-severe one with survival to adulthood. Herein we investigated whether a new modality that combines X-ray computer tomography with fluorescence tomography in one hybrid system can be employed to study internal bleedings in relation to bone fractures and obtain insights into disease progression. The disease phenotype was characterized on Aga2/+ vs. wild type mice between 6 and 9 days postnatal. Anatomical and functional findings obtained in-vivo were contrasted to the ex-vivo appearance of the same tissues under cryo-slicing.


Altered intestinal functions and increased local inflammation in insulin-resistant obese subjects: a gene-expression profile analysis.
Metabolic alterations relevant to postprandial dyslipidemia were previously identified in the intestine of obese insulin-resistant subjects. The aim of the study was to identify the genes deregulated by systemic insulin resistance in the intestine of severely obese subjects. Transcripts from duodenal samples of insulin-sensitive (HOMA-IR < 3, n = 9) and insulin-resistant (HOMA-IR > 7, n = 9) obese subjects were assayed by microarray (Illumina HumanHT-12). A total of 195 annotated genes were identified as differentially expressed between these two groups (Fold change > 1.2). Of these genes, 36 were found to be directly involved in known intestinal functions, including digestion, extracellular matrix, endocrine system, immunity and cholesterol metabolism. Interestingly, all differentially expressed genes (n = 8) implicated in inflammation and oxidative stress were found to be upregulated in the intestine of insulin-resistant compared to insulin-sensitive subjects. Metabolic pathway analysis revealed that several signaling pathways involved in immunity and inflammation were significantly enriched in differently expressed genes and were predicted to be activated in the intestine of insulin-resistant subjects. Using stringent criteria (Fold change > 1.5; FDR < 0.05), three genes were found to be significantly and differently expressed in the intestine of insulin-resistant compared to insulin-sensitive subjects: the transcripts of the insulinotropic glucose-dependant peptide (GIP) and of the β-microseminoprotein (MSMB) were significantly reduced, but that of the humanin like-1 (MTRNR2L1) was significantly increased. These results underline that systemic insulin resistance is associated with remodeling of key intestinal functions. Moreover, these data indicate that small intestine metabolic dysfunction is accompanied with a local amplification of low-grade inflammatory process implicating several pathways. Genes identified in this study are potentially triggered throughout the development of intestinal metabolic abnormalities, which could contribute to dyslipidemia, a component of metabolic syndrome and diabetes.


Investigating the implant position reproducibility of optical impressions obtained using an intraoral scanner and 3D-printed models fabricated using an intraoral scanner.
This study aims to examine the effect of the size of the intraoral scanning area on implant position reproducibility and compare the implant position reproducibility of plaster models fabricated using the silicone impression technique, the digital model of an intraoral scanner, and three-dimensional (3D)-printed models fabricated using an intraoral scanner. Scanbodies were attached to an edentulous model with six implants (master model) and were scanned using a dental laboratory scanner to obtain basic data. The plaster model was fabricated using the open-tray method (IMPM; n = 5). The master model was then scanned in various implant areas using an intraoral scanner to obtain data (IOSM; n = 5); the scanning data of six scanbodies were used to fabricate the 3D-printed models (3DPM; n = 5) using a 3D printer. Scanbodies were attached to the implant analogs of the IMPM and 3DPM models and data were obtained using a dental laboratory scanner. The basic data and IMPM, IOSM, and 3DPM data were superimposed to calculate the concordance rate of the scanbodies. The concordance rate of intraoral scanning decreased as the number of scanbodies increased. Significant differences were observed between the IMPM and IOSM data, and between the IOSM and 3DPM data; however, the IMPM and 3DPM data did not differ significantly. The implant position reproducibility of the intraoral scanner decreased with an increase in the scanning area. However, ISOM and 3DPM may provide higher implant position reproducibility than plaster models fabricated using IMPM.


The island pedicled anterolateral thigh (pALT) flap via the lateral subcutaneous tunnel for recurrent ischial ulcers.
Chronic recurrent ischial sores are an important cause of morbidity in paraplegics and geriatric patients. Compared to sacral and trochanteric ulcers, ischial sores are the most difficult to treat, with a low success rate following conservative therapy and a high recurrence rate after surgical treatment. We report the use of the pedicled anterolateral thigh (pALT) flap for reconstruction of a chronic ischial sore. The free ALT flap has an established role in reconstruction in the head and neck and extremities. However, there are few reports concerning its clinical applications for regional reconstruction. As a pedicled flap, it has been used in the primary reconstruction of the perineum, groin, anterior abdominal wall, thigh and ischium. We present the first reported case of a paraplegic man with a recurrent ischial sore treated successfully with an island pALT flap inset via a lateral subcutaneous approach. We discuss the indications and its role as a simple and reliable secondary reconstructive option in the treatment of recurrent ischial ulcers after first-line loco-regional surgical options have been exhausted.


Plasma metabolomics analysis of the effects of drinking soda water on hyperglycemia mice using ultrahigh-pressure liquid chromatography-quadrupole-time of flight-mass spectrometry.
The aim of this study was to evaluate the effects of a natural soda water [Shi Han Quan (SHQ)] on hyperglycemia and plasma metabolic profiling and explore the mechanism using metabolomics techniques. Kun-Ming mice weighing 26 ± 2 g were used for the hyperglycemia animal model with alloxan and divided into control, hyperglycemia (HG), and HG + SHQ soda water (SHQ) groups. The experiment lasted for 30 days. The plasma metabolomic profiling of mice was determined using ultrahigh-pressure liquid chromatography-quadrupole-time of flight-mass spectrometry. After the mice drank SHQ soda water, the levels of insulin and blood glucose were significantly lower in the SHQ group compared with the control group, and the level of insulin sensitivity [insulin sensitivity index (ISI)] was significantly higher in the SHQ group compared with the HG group. The mice in the different groups after SHQ intervention could be separated into distinct clusters, and nine major plasma metabolites with significant differences between groups were found closely associated with blood glucose and ISI. The metabolic pathway analysis of these metabolites involved abnormal fatty acid oxidation and phospholipid, acylcarnitine, and corticoid metabolism. The results suggested the metabolic changes and possible mechanism of SHQ improving the alloxan-induced HG, and the findings provided insights into the prevention and control of HG and diabetes.


Angiotensin II increases nerve-evoked contractions in mouse tail artery by a T-type Ca(2+) channel-dependent mechanism.
Angiotensin II (Ang II) increases sympathetic nerve-evoked contractions of arterial vessels. Here the mechanisms underlying this effect were investigated in mouse tail artery. Isometrically mounted segments of mouse distal tail artery were used to investigate the effects of endothelium denudation, blocking Ca(2+) channels and inhibiting superoxide signalling on Ang II-induced facilitation of nerve-evoked contractions. In addition, in situ amperometry was used to assess effects of Ang II on noradrenaline release. Ang II (0.1-1nM) increased nerve-evoked contractions but did not change noradrenaline release. Losartan (Ang II type 1 receptor antagonist), but not PD 123319 (Ang II type 2 receptor antagonist), blocked the facilitatory effect of Ang II on nerve-evoked contractions. Ang II increased vascular muscle reactivity to phenylephrine and UK-14304 (α1- and α2-adrenoceptor agonists, respectively). Endothelial denudation increased nerve-evoked contractions and reduced the facilitatory effect of Ang II on these responses. Efonidipine (L- and T-type Ca(2+) channel blocker) and NNC 55-0396 (T-type Ca(2+) channel blocker) also attenuated this effect of Ang II, while nifedipine (L-type Ca(2+) channel blocker) did not. Blockers of superoxide generation/signalling did not change the facilitatory effect of Ang II on nerve-evoked contractions. The findings indicate that Ang II increases the contribution of T-type Ca(2+) channels to neural activation of the vascular muscle. In addition, Ang II appears to reduce the inhibitory influence of the endothelium on nerve-evoked contractions.


Magnetic resonance imaging for the assessment of lingual thyroid.
A 43-year-old woman was evaluated because of a round tumor at the base of the tongue. Scintigraphy with 131I showed radionuclide uptake over the posterior part of the tongue but no uptake at all at the usual pretracheal location. Magnetic resonance imaging revealed a well defined round mass of high signal intensity, which was clearly delineated from adjacent muscular tissue.


The effects of 2,2-diethylallylacetamide on hepatic cytochromes in rats and in vitro.
The application of 0.15 and 0.3% of diethylallylacetamide (DA) in the drinking water to rats during 10 days increased the relative liver weight, the yield of hepatic microsomes, and cytochromes P-450 and b5. Single s.c. doses of 400 mg DA per kg reduced cytochrome P-450 concentrations in the hepatic endoplasmic reticulum of rats. This effect was considerably more pronounced in rats pretreated with phenobarbital. The activity of 5-aminolaevulinic acid synthesis in liver mitochondria, and total liver porphyrins increased. In incubations of metabolizing hepatic microsomes from rabbits pretreated with phenobarbital 75% of 0.1 mM DA was degraded after 1 h. The aerobic incubation of 0.1 mM DA with rabbit hepatic microsomes in the presence of NADPH produced 50% destruction of cytochrome P-450 within 1 h. Addition of EDTA revealed that a part of this destruction cannot be explained by accelerated lipid peroxidation.


Discrepancies between selected Pareto optimal plans and final deliverable plans in radiotherapy multi-criteria optimization.
Multi-criteria optimization provides decision makers with a range of clinical choices through Pareto plans that can be explored during real time navigation and then converted into deliverable plans. Our study shows that dosimetric differences can arise between the two steps, which could compromise the clinical choices made during navigation.


Vaginal photoplethysmography: methodological considerations.
Methodological considerations related to the use of vaginal photoplethysmography in the experimental investigation of physiological sexual arousal in women are discussed. Specific topics covered include the operation and use of the device, methods of data reduction and analysis, and the role of vaginal photoplethysmography in the study of female sexual arousal. A review of the literature focusing on methodological issues is also included.


Eye lens regeneration and the crystallins in the adult newt, Notophthalmus viridescens.
Upon lens removal, the adult Eastern Spotted newt, Notophthalmus viridescens, has the capacity to regenerate an ocular lens. Crystallins, proteins characteristic of the vertebrate lens, were studied from normal and 3-month regenerated adult newt lenses. When separated by high-performance liquid chromatography (HPLC) or Sephadex G-200SF column chromatography, the crystallins from normal and regenerated lenses were fractionated into what appear to be the classical four groups: alpha, beta High, beta Low, and gamma. Upon further examination by immunoelectrophoresis, the first peak contains both alpha and beta crystallins. This study provides evidence that most of the crystallins from the regenerated lenses share biochemical properties with those of the normal lens crystallins based on their native molecular weight, isoelectric point, and the molecular wt of their constituent polypeptides, indicating that the fidelity of gene expression in reactivated iris tissue is high. Some differences are found between normal and regenerated lens crystallins and are most obvious in the beta-crystallin region: the proportion of beta crystallins is decreased in regenerated lenses when the total proteins are fractionated by column chromatography and some of the beta-crystallin polypeptide chains found in normal lenses are missing from regenerated lenses. Iris epithelial cells are normally withdrawn from the cell cycle and are synthesizing a tissue-specific product, melanin. After lentectomy these cells dedifferentiate, redifferentiate into lens cells, and their progeny then synthesize different tissue-specific proteins, crystallins. Little is known about the specific mechanism(s) for the activation of gene expression in eukaryotes, but the regenerating lens suggests itself as a good model in which to study this biological problem.


One-Pot Solvothermal Synthesis of Bi4V2O11 as A New Solar Water Oxidation Photocatalyst.
Bi4V2O11 was prepared via a one-pot solvothermal method and characterized via XRD, Raman, XPS, Electrochemical impedance spectroscopy. The as-prepared Bi4V2O11 sample displays excellent photocatalytic activity towards oxygen evolution under light irradiation. The hierarchical structure is in favour of the spatial separation of photogenerated electrons and holes. Furthermore, the internal polar field also plays a role in improving the charge separation. Both of the two results are responsible for excellent activity of O2 evolution. The resulting hierarchical Bi4V2O11 sample should be very promising photocatalyst for the application of photocatalytic O2 evolution in the future.


The semiology of psychogenic nonepileptic seizures revisited: Can video alone predict the diagnosis? Preliminary data from a prospective feasibility study.
To investigate if, when, and to what extent visual information contained in a video-recorded event allows experienced epileptologists to predict the diagnosis of psychogenic nonepileptic seizures (PNES) without the aid of electroencephalography (EEG). Five neurologists actively practicing in epilepsy centers in Italy and the United States were asked to review 23 videos capturing representative events of 21 unselected consecutive patients admitted for long-term video-EEG monitoring (VEM). Four raters were blind to EEG and clinical information; one rater was not. They were requested to (1) rate the videos for quality and content; (2) choose among four diagnoses: (a) epileptic seizures (ES); (b) PNES; (c) Other nonepileptic seizures (NES; (syncope, movement disorder, migraine, etc.); (d) "Cannot Say"; and (3) explain in their own words the main reasons leading to the diagnosis of choice. All raters predicted the diagnosis correctly in 7 of 23 videos (all ES or PNES) (30.4%), whereas all raters failed in 5 of 23 cases (three Other NES, one PNES, one Cannot Say) (21.7%). The conditions that facilitate, and those that interfere with, a confident diagnosis were predictable. Degree of accuracy among raters was not uniform and was consistently better in three raters. Two among the four blind raters were as accurate as the rater who was not blinded. Interrater agreement was "moderate" (k = 0.52) for the overall group; "moderate" for ES (k = 0.53); "substantial" for PNES (k = 0.63); "fair" for Other NES (k = 0.21)-similar to the results obtained in a previous study evaluating the reliability of combined video-EEG. In about one third of cases, a confident diagnosis of PNES/ES can be established on clinical grounds based on video data alone. Our results benefit all affected patients, particularly those with no access to video-EEG monitoring units.


Preconceived notions about biosimilars-a French experience.
Since the arrival of the first biosimilar monoclonal antibodies into the market, many information has been circulating, leading to preconceived notions for patients and healthcare professionals. In a pressing economic context and faced with a growing number of available biosimilars, we (clinician, patient association, biologist, pharmacists, health economists) propose to take stock by trying to distinguish facts from misconceptions.


Quiescent optical solitons with complex Ginzburg-Landau equation having a dozen forms of self-phase modulation.
The current study focuses on the recovery of quiescent optical solitons through the use of the complex Ginzburg-Landau equation when the chromatic dispersion is rendered to be nonlinear. A dozen forms of self-phase modulation structures are taken into consideration. The utilization of the enhanced Kudryashov's scheme has led to the emergence of singular, dark, and bright soliton solutions. The existence of such solitons is subject to certain parametric restrictions, which are also discussed in this paper.


Characterisation and toxicological activity of three different Pseudo-nitzschia species from the northern Adriatic Sea (Croatia).
Diatoms of the genus Pseudo-nitzschia are cosmopolitans spread in seas and oceans worldwide, with more than 50 described species, dozens of which have been confirmed to produce domoic acid (DA). Here, we characterized and investigated the toxicological activity of secondary metabolites excreted into the growth media of different Pseudo-nitzschia species sampled at various locations in the northern Adriatic Sea (Croatia) using human blood cells under in vitro conditions. The results revealed that three investigated species of the genus Pseudo-nitzschia were capable of producing DA indicating their toxic potential. Moreover, toxicological data suggested all three Pseudo-nitzschia species can excrete toxic secondary metabolites into the surrounding media in addition to the intracellular pools of DA, raising concerns regarding their toxicity and environmental impact. In addition, all three Pseudo-nitzchia species triggered oxidative stress, one of the mechanisms of action likely responsible for the DNA damage observed in human blood cells. In line with the above stated, our results are of great interest to environmental toxicologists, the public and policy makers, especially in light of today's climate change, which favours harmful algal blooms and the growth of DA producers with a presumed negative impact on the public health of coastal residents.


Health care decision making in Southern County.
We combine two standard approaches to analyze power and influence in health policy formulation within a moderately large county in the south. Intrinsic methodologic weaknesses are discussed and several conclusions are drawn regarding power in the health care sector of that community. The most significant finding is the shift in power over time, away from the individuals to committees and health care organizations. The ignorance of most physicians about the broader health care issues that affect the community was reflected in their lack of recognition by others in the community as influential decision makers. The insular relationship of the university to the rest of the community was also noted. Past racial politics had a continuing effect on later health policy formulation. These findings are discussed in light of current and past issues. Because we had promised confidentiality to the persons we interviewed, fictitious names were given to the county, the institutions, and the interviewees.


Ultrasound imaging for the rheumatologist. XIII. New trends. Three-dimensional ultrasonography.
Despite its indubitable potential, ultrasonography still has limited diffusion in rheumatology related principally to the image acquisition process due to at least five main factors: the steep learning curve, lack of standardisation of the technique, intra- and inter-observer variability, time consumption and the high initial cost of top quality sonographic equipment. Of all these barriers, the first four are undoubtedly the most difficult to overcome. This review discusses the available evidence supporting the potential of three-dimensional ultrasound with high-frequency volumetric probe to overcome the first four barriers. The challenge to three-dimensional ultrasound is to prove itself to be a method that requires no particular skills that can be mastered in just a few minutes and is not operator-dependant [corrected]


Combined effects of agrochemical contamination and forest loss on anuran diversity in agroecosystems of east-central Argentina.
Agricultural expansion and intensification has led globally to a rapid landscape structure change and high agrochemical use resulting in habitat loss and degraded environmental quality. Co-occurrence of landscape change and agrochemical contamination threatens biodiversity and might have interactive effects especially for organisms with complex life-cycles such as amphibians. We evaluated effects of landscape structure and agrochemical contamination at different spatial scales on anurans in Entre Rios, Argentina. We selected 35 independent stream headwaters along an agricultural expansion and intensification gradient. We conducted anuran call surveys from spring 2012 to summer 2013 and obtained detection-non detection data to estimate mean richness and focal species occupancy. We quantified forest area and riparian forest width at two spatial scales (sub-basin and local reach scale). We measured nutrients and pesticides in water and sediment. We evaluated anuran response to landscape and contamination variables using GLMs for richness and single season single-species occupancy models for focal species. Anuran diversity increased with forest area and riparian forest width, and decreased at sites with herbicide and nutrient contamination, particularly glyphosate; 2,4-D and nitrates. Also, most focal frog species responded mainly to basin forest and 2,4-D. Negative effects of agrochemical contamination on anuran diversity was mitigated in areas with larger basin forest cover. Agricultural management should ensure the reduction of herbicide and fertilizer use, the sparing of adequate forested habitat within drainage areas, and preservation of riparian forests around anuran breeding habitat to reduce and mitigate the negative effects of agrochemical contamination on anurans diversity in agroecosystems.


Promotion of oxidative stress by L-tryptophan in cerebral cortex of rats.
Despite the significant brain abnormalities, the neurotoxic mechanisms of brain injury in hypertryptophanemia are virtually unknown. In this work, it was investigated the in vitro effect of l-tryptophan on various parameters of oxidative stress, namely spontaneous chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR) and glutathione (GSH) levels in cerebral cortex from 30-day-old rats. Tryptophan significantly increased chemiluminescence and TBA-RS measurements indicating that this amino acid induced lipid peroxidation in vitro. We also observed that tryptophan significantly decreased the brain antioxidant defenses by reducing the values of TRAP, TAR and GSH, reflecting that the overall content of antioxidants was reduced by tryptophan. Furthermore, the tryptophan-induced increase of TBA-RS was fully prevented by GSH and by combination of catalase plus superoxide dismutase, but not by the inhibitor of nitric oxide synthase N(omega)-nitro-L-arginine methyl ester (L-NAME). In case these findings also occur in human hypertryptophanemia or in other neurodegenerative diseases in which tryptophan accumulates, it is feasible that oxidative stress may be involved in the mechanism leading to the brain injury observed in patients affected by these disorders.


Increased melatonin levels in aqueous humor of patients with proliferative retinopathy in type 2 diabetes mellitus.
To report the association between melatonin levels in aqueous humor and serum, and diabetic retinopathy (DR) grade in type 2 diabetic patients. Aqueous humor and plasma samples from 26 patients with DR (in nonproliferative and proliferative stages) and 14 control subjects were collected during cataract surgery after 6 p.m. Melatonin concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). Melatonin levels were significantly higher in the aqueous humor of patients with proliferative diabetic retinopathy (PDR) [18.57±2.67 pg/mL (range 15.20-23.06) vs 13.63±2.71 pg/mL (range 10.20-20.20), P=0.0001], but not in those with nonproliferative retinopathy (NPDR) [13.79±2.56 pg/mL (range 9.80-20.10) vs 13.63±2.71 pg/mL (range 10.20-20.20), P=0.961] compared to controls. There was decrement in the plasma melatonin level of patients with PDR, but no significant differences between the plasma melatonin levels of the study groups [5.37±1.74 pg/mL (range 2.85-8.65) vs 6.11±1.90 pg/mL (range 3.13-9.41), P=0.293], or between control and DR groups [NPDR 6.11±1.90 pg/mL (range 3.13-9.41) vs control 6.15±1.91 pg/mL (range 2.18-9.86); PDR (5.37±1.74 pg/mL (range 2.85-8.65) vs control 6.15±1.91 pg/mL (range 2.18-9.86), P=0.808, P=0.264]. Elevated melatonin levels in aqueous humor in PDR may indicate the level to be associated with DR severity.


Control of interferon mRNA levels and interferon yields in butyrate and 5'-bromodeoxyuridine-treated Namalwa cells.
Treatment of Namalwa cells with butyrate or 5'-bromodeoxyuridine (BrdUrd) before induction with Sendai virus caused an increase in the production of both interferon (IFN) and interferon mRNA (IFN mRNA). However, the increase in IFN mRNA did not completely account for the increase in IFN yield. The treatments did not affect the time course of IFN mRNA transcription and translation, or the association of IFN mRNA with polysomes. Likewise, the treatments did not alter the post-translational fate of the IFN produced. We conclude that butyrate and BrdUrd affect IFN production at the level of transcription or processing of IFN mRNA and suggest that increased efficiency of translation provides an additional level of control.


Mindset matters: how mindset affects the ability of staff to anticipate and adapt to Artificial Intelligence (AI) future scenarios in organisational settings.
Any first step in organisational adaptation starts with individuals' responses and willingness (or otherwise) to change an aspect of themselves given the transcontextual settings in which they are operating (Bateson in Small arcs of larger circles: framing through other patterns, Triarchy Press, Axminster, 2018). This research explores the implications for organisational adaptation strategies when Artificial Intelligence (AI) is being embedded into the ecology of the organisation, and when employees have a dominant fixed or growth mindset (Dweck in Mindset: changing the way you think to fulfil your potential. Robinson, London, 2017). Research participants were supplied with a single scenario based in 2030, where-as a result of Artificial Intelligence technology implementation-employees were going to be displaced. Using Torbert's (Organizational wisdom and executive courage, New Lexington Press, San Francisco, 1998) 'first, second and third person' research theory, participants were asked to independently review their thoughts, sense, and image of the future from a fixed mindset position (considered to be the worst case), then from a growth mindset perspective (best case), and then do the same collectively. Five key findings are outlined which support the principle that having a growth mindset is a key component of adaptive capacity and futures literacy. The five key findings conclude that AI adaptation processes need to include compassion and authenticity, embodiment, fundamental needs and motivations, mutual learning and considering what lies beyond the edges of the organisation (Bateson in Small arcs of larger circles: framing through other patterns, Triarchy Press, Axminster, 2018).


Clinical impact of cerebrospinal fluid Gram stain and culture testing: A retrospective cohort study.
Stewardship of microbiological tests can improve laboratory efficiency. One indicator of appropriate test stewardship is test impact on patient management decisions. We sought to assess the impact of cerebrospinal fluid (CSF) Gram stain and culture results on treatment decisions. Our hypothesis was that CSF Gram stain and culture have low impact on patient management. CSF specimens received at a tertiary microbiology laboratory between January 1, 2013, and December 31, 2013, were included. Clinical information and data on antibiotic treatment before CSF collection, antibiotic treatment after CSF Gram stain results, and antibiotic treatment after CSF culture results were collected. Ethics approval for secondary use of data was obtained. We received 242 CSF specimens for Gram stain and culture during the study period; 120 were excluded (84 from children, 2 from indwelling ventricular drains, 12 collected at outside hospitals, 21 data missing, 1 duplicate). No Gram stains or cultures were positive among patients not already treated empirically. The number needed to test to influence treatment was 17 for Gram stain (11 for abnormal cytochemistry, 29 for normal cytochemistry) and 6 for culture (3 for abnormal cytochemistry, 6 for normal cytochemistry). CSF Gram stain and culture are rarely positive and are being performed on inappropriate specimens. CSF results never prompt physicians to start treatment, so results are affecting not outcome but antibiotic stewardship. Negative CSF culture often leads to discontinuation of antibiotics. Labs could consider rejecting CSF Gram stain if cytochemistry is normal.


Strong, tough, rapid-recovery, and fatigue-resistant hydrogels made of picot peptide fibres.
Hydrogels are promising soft materials as tissue engineering scaffolds, stretchable sensors, and soft robotics. Yet, it remains challenging to develop synthetic hydrogels with mechanical stability and durability similar to those of the connective tissues. Many of the necessary mechanical properties, such as high strength, high toughness, rapid recovery, and high fatigue resistance, generally cannot be established together using conventional polymer networks. Here we present a type of hydrogels comprising hierarchical structures of picot fibres made of copper-bound self-assembling peptide strands with zipped flexible hidden length. The redundant hidden lengths allow the fibres to be extended to dissipate mechanical load without reducing network connectivity, making the hydrogels robust against damage. The hydrogels possess high strength, good toughness, high fatigue threshold, and rapid recovery, comparable to or even outperforming those of articular cartilage. Our study highlights the unique possibility of tailoring hydrogel network structures at the molecular level to improve their mechanical performance.


Ulotaront: review of preliminary evidence for the efficacy and safety of a TAAR1 agonist in schizophrenia.
Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist in Phase 3 clinical development for the treatment of schizophrenia. Ulotaront was discovered through a unique, target-agnostic approach optimized to identify drug candidates lacking D2 and 5-HT2A receptor antagonism, while demonstrating an antipsychotic-like phenotypic profile in vivo. The mechanism of action (MOA) of ulotaront is thought to be mediated by agonism at TAAR1 and serotonin 5-HT1A receptors. Ulotaront has completed two Phase 2 trials (4-week acute study and 26-week open-label extension) which led to Breakthrough Therapy Designation from the US Food and Drug Administration for the treatment of schizophrenia. In the double-blind, placebo-controlled, acute study, ulotaront was associated with significant (p < 0.001) improvement in Positive and Negative Syndrome Scale (PANSS) total score (effect size [ES]: 0.45), with improvements vs. placebo also observed across secondary endpoints. Post-hoc analyses of the acute trial revealed additional evidence to support the effect of ulotaront on negative symptoms. In the 4-week study, ulotaront was well-tolerated, with an incidence of adverse events (AEs) numerically lower compared to placebo (45.8% vs. 50.4%; with a number needed to harm [NNH] for individual ulotaront AEs all > 40). The open-label extension demonstrated further improvement across schizophrenia symptoms and confirmed the tolerability of ulotaront, with a 6-month completion rate of 67%. Based on current data, ulotaront shows potential to be a first-in-class TAAR1 agonist for the treatment of schizophrenia with a safety and efficacy profile distinct from current antipsychotics.


Parents' views on medical decisions related to life and death for their ageing child with profound intellectual and multiple disabilities: A qualitative study.
The increased life expectancy of persons with profound intellectual and multiple disabilities (PIMD) raises questions regarding the medical decisions related to life and death, made on their behalf during their later lives. However, little is known about how parents make such decisions for their ageing child. Explore parents' views on medical decisions related to life and death for their ageing child with PIMD. We interviewed 27 parents of persons with PIMD (≥ 15 years) and analyzed the data thematically. Parents who were convinced that their ageing child's quality of life (QoL) was good, stated that their child "deserved the same treatment as any other person". Others rejected life-prolonging treatments for their child because they believed such treatment would diminish their child's QoL. Some of the parents who thought their child's QoL was poor, mentioned that withholding treatment is only an option in a crisis situation and contemplated other options to shorten their child's life. Parents feel equipped to take on a central role in medical decisions related to life and death for their ageing child with PIMD, and desire understanding from medical professionals for their views on their child's interests, which sometimes includes physician-assisted death.


The complete mitochondrial genome of Eulaelaps huzhuensis (Mesostigmata: Haemogamasidae).
Some mites of the family Haemogamasidae can transmit a variety of zoonotic diseases and have important public health and safety implications. Currently, however, little attention has been paid to molecular data of Haemogamasidae species, limiting our understanding of their evolutionary and phylogenetic relationships. In this study, the complete mitochondrial genome of Eulaelaps huzhuensis was determined for the first time, and its genomic information was analyzed in detail. The mitochondrial genome of E. huzhuensis is 14,872 bp in length with 37 genes and two control regions. The base composition showed a distinct AT preference. Twelve protein-coding genes have a typical ATN as the start codon, and three protein-coding genes have incomplete stop codons. During the folding of tRNA genes, a total of 30 mismatches occurred, and three tRNA genes had an atypical cloverleaf secondary structure. The order of the E. huzhuensis mitochondrial genome arrangement is a new type of rearrangement in Mesostigmata. The phylogenetic analysis confirmed that the family Haemogamasidae is a monophyletic branch and does not belong to a subfamily of the Laelapidae. Our results lay the foundation for subsequent studies on the phylogeny and evolutionary history of the family Haemogamasidae.


Influence of hypodermic needle dimensions on subcutaneous injection delivery--a pig study of injection deposition evaluated by CT scanning, histology, and backflow.
Thinner and shorter needles for subcutaneous administration are continuously developed. Previous studies have shown that a thinner needle causes fewer occurrences of painful needle insertions and that a shorter needle decreases the occurrence of painful intramuscular injections. However, little is known about local drug delivery in relation to needle length and thickness. This study aimed to compare deposition depth and backflow from three hypodermic needles of 3 mm 34G (0.19 mm), 5 mm 32G (0.23 mm), and 8 mm 30G (0.30 mm) in length and thickness. Ex vivo experiments were carried out on pigs, in neck tissue comparable to human skin at typical injection sites. Six pigs were included and a total of 72 randomized injections were given, i.e. 24 subcutaneous injections given with each needle type. Accordingly, 400 μL was injected including 70% NovoRapid(®) (Novo Nordisk A/S, Bagsvμrd, Denmark) and 30% Xenetix(®) (Guerbet, Villepinte, France) contrast including 1 mg/mL Alcian blue. Surgical biopsies of injection sites were sampled and computer topographic (CT)-scanned in 3D to assess deposition and local distribution. Biopsies were prepared and stained to evaluate deposition in comparison to the CT-scanning findings. The backflow of each injection was collected with filter paper. The blue stains of filter paper were digitized and volume estimated by software calculation vs. control staining. CT-scanning (n = 57) and histology (n = 10) showed that, regardless of injection depth, the bulk of the injection was in the subcutaneous tissue and did not propagate from subcutis into dermis. With the 8 mm 30G needle all injections apart from one intramuscular injection were located in the subcutaneous layer. The volume depositions peaked in 4-5 mm depth for the 3 mm 34G needle, in 5-6 mm depth for the 5 mm 32G needle, and in 9-10 mm depth for the 8 mm 30G needle. In general, injection depositions evaluated by histology and CT-scans compared well for the individual biopsies. The amount of backflow (n = 69) from the 3 mm 34G needle was smaller (P < 0.05) as compared to the 5 mm 32G and the 8 mm 30G needles. Analysis showed a correlation between backflow and the needle's outer dimension with the needle diameter being the pivotal parameter. Furthermore, CT-scanning and histology confirmed that local propagation of the injection and final distribution followed a route of less mechanical resistance as determined by connective tissue barriers preset in the site of injection. Needles as short as 3 mm efficiently delivered injections into the subcutaneous target. The amount of backflow was smaller with thinner needles. Local distribution was variable and determined by mechanical barriers preset in the tissue. CT-scans and histology were concordant.


Iron-sulfur cluster sensor-regulators.
Regulatory proteins that contain an iron-sulfur cluster cofactor constitute a group that is growing both in number and importance, with a range of functions that include sensing of molecular oxygen, stress response, and iron regulation. In all cases, the cluster plays a central role, as a sensory module, in controlling the activity of the regulator. In some cases, the cluster is required for the protein to attain its regulatory form, while in others the active form requires loss or modification of the cluster. In this way, nature has exploited the inherent reactivity of iron-sulfur clusters. Here, we focus on recent advances that provide new insight into the remarkable chemistries exhibited by these regulators, and how they achieve the required levels of sensitivity and specificity.


Repair of tricuspid valve insufficiency in patients undergoing double (aortic and mitral) valve replacement. Perioperative mortality and long-term (1 to 20 years) follow-up in 109 patients.
Between 1965 and 1984, 109 patients underwent simultaneous aortic and mitral valve replacement and tricuspid valve repair at the Mayo Clinic, with a perioperative mortality of 21%. The only variable predictive of perioperative mortality on multiple regression analysis was New York Heart Association class IV disability. The median follow-up was 5.6 years (range 1 to 20 years). Cumulative 5-, 10-, and 15-year survival rates in patients discharged from the hospital were 70% +/- 5%, 42% +/- 6%, and 33% +/- 7%. Multivariate analysis identified advanced age and class IV disability as significant predictors of poor survival. Five-year survival rates were similar in patients undergoing operation between 1965 and 1974 and after 1975, despite an increase in age and in the severity of preoperative symptoms in the recent group. Late mortality was due to sudden death in 38% of the patients, heart failure in 21%, reoperation in 5%, endocarditis in 2%, and thromboembolism and bleeding in 4%. Late complications included systemic emboli in 22% (embolism rate 4.5 events/100 patient-years), bleeding in 17%, reoperation in 14%, myocardial infarction in 8%, permanent pacemaker implantation in 5%, and infective endocarditis in 3%. Of 43% of the patients still alive, 79% are in class I or II.


Influence of TEMPO-oxidized cellulose nanofibril length on film properties.
Various mechanical disintegration conditions in water were applied to 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized cellulose to prepare TEMPO-oxidized cellulose nanofibrils (TOCNs) of uniform widths ∼4 nm but with three different average lengths, 200, 680, and 1100 nm. The viscosity average degrees of polymerization of the TOCNs were 250, 350, and 400, respectively. Self-standing TOCN and TOCN-coated poly(ethylene terephthalate) (PET) and poly(lactic acid) (PLA) films were prepared, and the optical, mechanical and gas-barrier properties of the films were evaluated in terms of nanofibril length. Only small differences in density, water content, and elastic modulus of the films were observed but TOCN films prepared from longer nanofibrils clearly showed higher tensile strengths, elongations at break and crystallinity indices. The oxygen barrier properties of the TOCN-coated PET and PLA films increased with increasing nanofibril length. In contrast, nanofibril length had almost no influence on water vapor-barrier properties.


An asymmetric bulging of the chest as a leading sign of a cardiac fibroma in a child.
A 17-month-old child with an asymmetrical bulging of the chest due to an intramural fibroma of the heart is described. The clinical symptoms that may be caused by cardiac tumours are discussed. To detect these tumours several investigations can be performed, of which echocardiography is the most specific. Surgical resection of these tumours should be attempted, even if a complete resection is not possible.


Unique problems for the design of the first trials of transplanting porcine kidneys into humans.
Over the past year, 3 scientific teams conducted experiments of genetically edited porcine organs into human recipients, 3 of whom were deceased and 1 living. In this editorial, we describe challenges for the design of initial xenotransplantation clinical trials and focus on patient selection, consent, and requisite post-transplant follow-up. Given the uncertain clinical benefit of xenotransplantation, we propose that patient selection criteria might include novel elements, such as approaching patients who have a low quality of life and a strong aversion to continued dialysis therapy. We set expectations related to the importance of informing and protecting family members and medical teams who could be exposed to zoonotic viral infection from the donor organ and/or receive unwanted publicity. Meeting these challenges in trial design and oversight will require multidisciplinary expertise, a conceptual model that extends beyond the individual patient, and creative collaboration between scientists and regulatory agencies.


Struggles between the body and machine: the paradox of living with a home haemodialysis machine.
This study explored the life-world of individuals being treated for end stage renal disease with a home haemodialysis machine (HHDM). A phenomenological framework was employed to gain an understanding of the lived-body in relation to the HHDM in order to assist in the planning of future social work interventions. A purposive sample of three participants who had each experienced various lengths of HHDT, were interviewed using two semi-structured in-depth interviews, one week apart. Interviews were conducted at a place of the participant's choice. Participants were asked to speak about their experience of HHDT and how it related to their bodily experience. The findings were interpreted using interpretive phenomenological analytic methods. The central theme that arose from the data was "Struggles between the body and machine". This theme spoke to paradoxical dilemma of living with a life saving machine that you have no control over. Implications suggest that the machine's tendency to be personified, means that it be considered as family member in social assessment. Emotional support to patients should acknowledge the machines dehumanizing tendencies and as well as the issue of its personification. Finally, a patients unmet needs may turn to subversion if not addressed by staff, suggesting that a systematic process to empower patients be established.


Acute renal failure.
Acute renal failure is divided into its classic parts: prerenal azotemia, postrenal azotemia (obstruction), and renal azotemia (including acute tubular necrosis). The division of acute tubular necrosis into the ischemic and toxic varieties is supplemented by an analysis of toxic varieties into those caused by antibiotics, radiologic contrast agents, chemotherapeutic-immunosuppressive agents, heavy metals, organic solvents, etc. Acute tubular necrosis caused by hemoglobin and myoglobin is described in detail. The importance of urinalysis and the urinary indices in distinguishing prerenal azotemia from acute tubular necrosis is stressed. Finally, current prognosis and treatment are reviewed.


Understanding the Difference Between Healthcare Informatics and Healthcare Data Analytics in the Present State of Health Care Management.
The purpose of this article is to perform a scientific analysis of the definitions associated with healthcare informatics and healthcare data analytics. Additionally, the authors attempt to redefine the scientific pursuit of healthcare informatics and healthcare data analytics. This commentary can assist the thinking of informaticians and data analysts working in healthcare management and practice. The authors also provide a brief insight on the possible future direction of informatics and analytics associated with healthcare.


Metabolic engineering of Saccharomyces cerevisiae for linalool production.
To engineer the yeast Saccharomyces cerevisiae for the heterologous production of linalool. Expression of linalool synthase gene from Lavandula angustifolia enabled heterologous production of linalool in S. cerevisiae. Downregulation of ERG9 gene, that encodes squalene synthase, by replacing its native promoter with the repressible MET3 promoter in the presence of methionine resulted in accumulation of 78 µg linalool l(-1) in the culture medium. This was more than twice that produced by the control strain. The highest linalool titer was obtained by combined repression of ERG9 and overexpression of tHMG1. The yeast strain harboring both modifications produced 95 μg linalool l(-1). Although overexpression of tHMG1 and downregulation of ERG9 enhanced linalool titers threefold in the engineered yeast strain, alleviating linalool toxicity is necessary for further improvement of linalool biosynthesis in yeast.


Pressurized liquid extraction as a novel sample pre-treatment for trace element leaching from biological material.
Pressurized liquid extraction (PLE), commonly used for organic compounds extraction, has been applied for trace element leaching from marine biological material in order to determine major and trace elements (Al, As, Cd, Co, Cu, Fe, Hg, Li, Mn, Pb, Se, Sr, V and Zn). The released elements by formic acid PLE have been evaluated by inductively coupled plasma-optical emission spectrometry (ICP-OES). Different variables, such as formic acid concentration, extraction temperature, static time, extraction steps, pressure, mean particle size and diatomaceous earth (DE) mass/sample mass ratio were simultaneously studied by applying an experimental design approach (Plackett-Burman design (PBD) and central composite design (CCD)). Results showed that the extraction temperature was statistically significant (confidence interval of 95%) for most of the elements (high metal releasing was achieved at high temperatures). In addition, formic acid concentration was also statistically significant (confidence interval of 95%) for metals such as Cd and Cu. Most of the metals can be extracted using the same PLE operating conditions (formic acid concentration of 1.0 M, extraction temperature at 125 degrees C, static time of 5 min, one extraction step, extraction pressure at 500 psi and DE mass/sample mass ratio of 2). Taking in mind PLE requirements at the optimised operating conditions (125 degrees C), a time of 6 min is needed to pre-heat the cell. Therefore, the PLE assisted multi-element leaching is completed after 12 min. Analytical performances, such as limits of detection and quantification, repeatability of the over-all procedure and accuracy, by analysing GBW-08571, DORM-2, DOLT-3 and TORT-2 certified reference materials, were finally assessed.


Editorial Commentary: Risks Versus Benefits.
As orthopaedic surgeons, we are constantly weighing the risks versus benefits of the procedures we may perform in our patients. The study by Werner et al. can be used to better inform our patients of the risk of undergoing arthroscopy of the elbow, allowing the orthopaedic surgeon to better weigh the risks versus benefits of the procedure.


Lymphomatoid granulomatosis: report of a case without pulmonary lesions and with ischemic colitis, probably a sequel to granulomatosis.
This article describes a case of lymphomatoid granulomatosis without active pulmonary involvement of stigmata of healed granulomatous lesions in the lungs. The patient had ischemic segmental colitis due to mesenteric arterial intimal fibrosis, which we interpreted as spontaneously regressed granulomatous involvement of the mesentery. The report deals with the lack of pulmonary involvement and regression of lesions in lymphomatoid granulomatosis.


Stimulation of lymphocyte proliferation and inhibition of nitric oxide production by aqueous Urtica dioica extract.
The immunomodulatory and antiinflammatory activities of aqueous Urtica dioica extract were investigated for their effect on the mitogenic response of murine splenocytes and nitric oxide production by murine peritoneal macrophages in vitro. It was found that this extract stimulated the proliferation of T-lymphocytes and suppressed NO production in lipopolysaccharide-stimulated macrophages without affecting cell viability.


Brief exposure to hyperoxia depletes the glial progenitor pool and impairs functional recovery after hypoxic-ischemic brain injury.
Patterns of hypoxic-ischemic brain injury in infants and children suggest vulnerability in regions of white matter development, and injured patients develop defects in myelination resulting in cerebral palsy and motor deficits. Reperfusion exacerbates the oxidative stress that occurs after such injuries and may impair recovery. Resuscitation after hypoxic-ischemic injury is routinely performed using 100% oxygen, and this practice may increase the oxidative stress that occurs during reperfusion and further damage an already compromised brain. We show that brief exposure (30 mins) to 100% oxygen during reperfusion worsens the histologic injury in young mice after unilateral brain hypoxia-ischemia, causes an accumulation of the oxidative metabolite nitrotyrosine, and depletes preoligodendrocyte glial progenitors present in the cortex. This damage can be reversed with administration of the antioxidant ebselen, a glutathione peroxidase mimetic. Moreover, mice recovered in 100% oxygen have a more disrupted pattern of myelination and develop a static motor deficit that mimics cerebral palsy and manifests itself by significantly worse performance on wire hang and rotorod motor testing. We conclude that exposure to 100% oxygen during reperfusion after hypoxic-ischemic brain injury increases secondary neural injury, depletes developing glial progenitors, interferes with myelination, and ultimately impairs functional recovery.


Mutagenicity of instant coffee and its interaction with dimethylnitrosamine in the micronucleus test.
The mutagenicity of instant coffee and its interaction with dimethylnitrosamine (DMN) were examined in mice using the micronucleus test. Although neither a single nor multiple administration of instant coffee by gavage induced a significant rise in micronucleated cells over the dose range tested (100-2500 mg/kg), there was a tendency for the number of micronucleated cells to increase in a dose-related fashion. When coffee was administered with DMN, the difference in the frequency of micronucleated cells was small in comparison to a single treatment with DMN alone, thus indicating a lack of synergism between coffee and DMN.


Administrative costs in health care-A scoping review.
Administrative costs (AC) are a relevant spending category in health care, and several approaches exist on how to define and measure them. Based on available AC studies, this paper aims to provide a map for this multifaceted research topic. A scoping review was conducted using the databases MEDLINE, EconLit, and Business Source Premier. Literature was screened focussing on the research question: What is known about the methodology of AC research from scientific publications? Definition concepts mostly rely on national cost documentations. The international cost reporting framework of the Systems of Health Accounts was a critical reference point in six studies. Indications on how to operationalise AC independently from periodical cost reports were suggested by ten publications. In this context, time and full time equivalents are the most common cost measurements. The results indicate a lack of evidence regarding patients' perceptions of administrative issues in health care. Also, research on administrative impact on working conditions for health care employees beyond hospitals and physicians' offices is underrepresented. A systematic approach to reporting AC studies is needed. Reporting should include the appointment of entities actually empowered to change administrative resource usage. This would help to promote principles of a balanced administration.


A new species of Ituglanis Costa & Bockmann, 1993 (Siluriformes: Trichomycteridae) endemic to the Tramandaí-Mampituba ecoregion, southern Brazil.
Ituglanis boitata, new species, is described from the rio Tramandaí system and rio Mampituba and Araranguá basins, southern Brazil. This new species is distinguished from congeners with the exception of I. bambui, I. boticario, I. paraguassuensis and I. proops by the supraorbital canal of the cephalic laterosensory system interrupted between nasal and frontal sections and the presence of pore s2 (vs. supraorbital canal uninterrupted and pore s2 absent). Ituglanis boitata differs from these species in osteological characters, measurements and body coloration. Ituglanis boitata presents a noticeable endemism in the Tramandaí-Mampituba freshwater ecoregion, a recognized biogeographic unit for freshwater fishes including other 22 endemic species. A discussion about the intraspecific variation in the cephalic laterosensory system within Trichomycterinae is also provided.


Endoscopic treatment of bronchopleural fistula using ethyl-2-cyanoacrylate: A report of two cases.
Bronchopleural fistula (BPF) is a serious complication after lung resection or chronic empyema. BPF often causes severe pneumonia or fatal airway bleeding due to bronchoarterial fistula. Although BPF often requires surgical treatment, another, more conservative treatment option is endoscopic bronchial occlusion for non-operable patients. Many endoscopic treatments have been reported. We report here two patients with BPF who underwent endoscopic bronchial occlusion. Patient 1 had postoperative BPF with empyema and Patient 2 had BPF due to chronic empyema. Because the BPF in Patient 1 was small, it could be successfully treated by endobronchial occlusion using only ethyl-2-cyanoacrylate. In contrast, because the BPF in Patient 2 was large, it could not be treated by endobronchial occlusion using ethyl-2-cyanoacrylate alone; it was successfully treated by endobronchial occlusion using the combination of ethyl-2-cyanoacrylate and a silicone spigot (endobronchial Watanabe spigot, EWS). When we attempt endoscopic bronchial occlusion with BPF for non-operable patients, ethyl-2-cyanoacrylate may be an option for small fistulas, while the combination of EWS and ethyl-2-cyanoacrylate may be suitable for large fistulas.