POU-domain gene expression in the gastrointestinal tract.
The process of self-renewal which occurs in the gastrointestinal epithelium is greatly amplified and accelerated during the intestinal adaptation which occurs in the residual ileum after massive small bowel resection (MSBR). As with growth and development, these processes must involve the coordinated regulation of many genes. Several families of nuclear proteins are known to be involved in the control of gene expression during development including the POU-domain genes; their expression has not been characterized in the gastrointestinal tract during normal cellular renewal or adaptation, and POU-domain encoding cDNAs were cloned from ileal RNA. Three known genes were cloned: Oct-1, Brn-1 and Tst-1 but no novel members of this gene family were identified. The encoded sequence for rat Oct-1 differs from that previously reported. Oct-1 is relatively ubiquitously expressed with increased expression during both development and adaptation. Minimal expression of Tst-1 was observed. Brn-1 exhibits limited expression in the adult gastrointestinal tract but may play a role in the fetal gastrointestinal tract.


Benznidazole treatment of chagasic encephalitis in pregnant woman with AIDS.
We report a case of chagasic meningoencephalitis reactivation in a pregnant woman co-infected with Trypanosoma cruzi and HIV that was successfully managed with benznidazole and highly active antiretroviral therapy. Early diagnosis enabled rapid specific treatment that improved the health of the patient and her baby.


Loss of antigens from immunoblotting membranes.
Immunoblotting of PAGE-separated proteins is widely used. After electrophoretically transferring proteins from PAGE gels, sites on the membrane which are unoccupied are blocked or quenched with excess protein. The sensitivity of the immunoblotting technique is in part dependent on the amount of antigen associated with the membrane. We have investigated the loss of blotted proteins during blocking of various membranes with milk. Transblotted proteins are lost from nitrocellulose membranes (NC) (0.45 microns) in proportion to the amount of milk in the blocking solution and loss increases with time. When 5% milk was used as the blocking solution the amount lost was about 10% within 1 h and approached 25% at 24 h. This loss was nonselective and involved blotted antigens of a wide range of Mr. This time- and concentration-dependent relationship for the loss of transblotted proteins was tested with four immunoblotting membranes: Immobilon-P (Millipore), NitroPlus-2000 (MSI), and NC (0.2 microns and 0.45 microns pore size). NC (0.2 microns) gave the best results with the lowest percentage loss at 1 h (less than 5%). We recommend using NC (0.2 microns) and blocking with 0.5% milk for 30 min to minimize the loss of antigens from immunoblotting membranes.


Improving the biological activity, functional properties, and emulsion stability of soybean meal hydrolysate via covalent conjugation with polyphenol.
The use of by-products as functional components in food production is gaining popularity. This study investigated the structure, biological activity, interaction force, and emulsion stability of soybean meal hydrolysate (SMHs) after covalent conjugation with proanthocyanidin (PC), epigallocatechin (EGCG), gallic acid (GA), and caffeic acid (CA). SDS-PAGE confirmed the formation of SMHs-polyphenol conjugates. Structural analysis indicates unfolding and disordered-structure formation. This transformation directly influenced the antioxidant activity and emulsification of SMHs. The antioxidant and emulsifying properties of all covalent complexes were superior to SMHs, in order of SMHs-PC, SMHs-EGCG, SMHs-GA, and SMHs-CA. Among, SMHs-PC conjugates displayed the highest antioxidant activity (ABTS•+ and DPPH radical scavenging capacities of 89.33% and 52.71%, respectively), total polyphenol content (235.10 mg/g), and emulsification activity (EAI) and stability (ESI) values (109.27 m2/g and 135.05 min, respectively). Moreover, SMHs-PC emulsion showed the smallest particle size (467.20 nm), highest viscosity (520.19 Pa.s), highest protein adsorption (94.33%), and lowest release rate of free fatty acids (FFAs) (18.61%) after digestion. These results provided valuable information for the use of modified SMHs as emulsifiers, which is a promising approach for increasing the value of soybean meal.


A 3D-QSAR study on ginkgolides and their analogues with comparative molecular field analysis.
Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) paradigm was used to study the correlation between the physicochemical properties and the in vitro bioactivities of ginkgolide analogues. The correlation derived from CoMFA analysis has a good predictive capability. Based on the result of CoMFA analysis, we designed some compounds. Pharmacological assay indicated that three of these new designed compounds are 2 and 4 times more potent than that of ginkgolides.


In vivo confocal imaging of the retina in animal models using scanning laser ophthalmoscopy.
Scanning-laser ophthalmoscopy is a technique for confocal imaging of the eye in vivo. The use of lasers of different wavelengths allows to obtain information about specific tissues and layers due to their reflection and transmission characteristics. In addition, fluorescent dyes excitable in the blue and infrared range offer a unique access to the vascular structures associated with each layer. In animal models, a further enhancement in specificity can be obtained by GFP expression under control of tissue-specific promotors. Important fields of application are studies in retinal degenerations and the follow-up of therapeutic intervention.


Stress Exposure and Maternal Depression as Risk Factors for Symptoms of Anxiety and Depression in Adolescents.
Little research has explored the implications of stress inside and outside of the family as a risk factor for psychological symptoms in adolescents of depressed mothers. In a sample of 115 adolescents and their mothers with and without depression histories, adolescents' family and peer stress exposure was measured through the Responses to Stress Questionnaire, and adolescents' anxious/depressed symptoms were measured with the Youth Self Report and Child Behavior Checklist. Mothers reported their current depression symptoms on the Beck Depression Inventory-II. Results suggest that adolescents of mothers with depression histories and current depression symptoms experience more family and peer stress than adolescents of nondepressed mothers. In multiple linear regression analyses, current maternal depression symptoms moderated the relation between adolescent peer stress and adolescent anxious/depressed symptoms, such that peer stress was associated with anxious/depressed symptoms when maternal depression symptoms were average or high, but not when maternal depression symptoms were low.


Selective chromosomal damage and cytotoxicity of 125I-labeled monoclonal antibody 17-1a in human cancer cells.
A monoclonal antibody, 17-1a, which reacts with antigen expressed in human colon cancers was radiolabeled in high specific activity with 125I. The combination of the antibody and this radionuclide was observed to elicit specific cellular damage after being internalized into cells of the SW1116 human colon cancer cell line. The degree of internalization was quantitatively measured and found to increase over time to 49% after a 48-h incubation period. During this period, significant chromosome aberrations were observed in the SW1116 cell line due to the Auger electrons of 125I. This damage was not observed using Na125I, a nonimmunoreactive radiolabeled antibody, or cells which did not contain the requisite antigen. The number of chromosomal aberrations increased with increasing radioactive concentration of 125I-17-1a. The nuclear damage resulted in specific cellular cytotoxicity and decreased cell survival of SW1116 cells exposed to various concentrations of 125I-17-1a.


Changes in the metrial gland of the rat uterus following ovariectomy on day 10 of pregnancy.
Rats were subjected to ovariectomy or a control operation on day 10 of pregnancy and light and electron microscope studies carried out to examine the cells of the decidua basalis and the mesometrial triangle. Degeneration of the decidua basalis was rapid but proliferation in the mesometrial triangle and differentiation of the typical granulated cells continued for some time, and resulted in the formation of a metrial gland. The earliest effect noted in the metrial gland was the appearance of inclusions in the fibroblast-like stromal cells one day after ovariectomy. During the next four days many stromal cells became packed with a variety of inclusions and it is suggested that some of these may represent phagocytosed cellular debris. Some debris appeared to be in intercellular spaces and was probably derived from granulated cells. Some granulated cells appeared to develop apparently empty vacuoles and this may be a preliminary stage in degeneration. Although granulated cells decreased to become very few in number five days after ovariectomy, the precise mechanism of their loss and the relationship of this to the hormonal environment could not be established.


Homeostatic Regulation of the Duox-ROS Defense System: Revelations Based on the Diversity of Gut Bacteria in Silkworms (Bombyx mori).
The Duox-ROS defense system plays an important role in insect intestinal immunity. To investigate the role of intestinal microbiota in Duox-ROS regulation herein, 16S rRNA sequencing technology was utilized to compare the characteristics of bacterial populations in the midgut of silkworm after different time-periods of treatment with three feeding methods: 1-4 instars artificial diet (AD), 1-4 instars mulberry leaf (ML) and 1-3 instars artificial diet + 4 instar mulberry leaf (TM). The results revealed simple intestinal microbiota in the AD group whilst microbiota were abundant and variable in the ML and TM silkworms. By analyzing the relationship among intestinal pH, reactive oxygen species (ROS) content and microorganism composition, it was identified that an acidic intestinal environment inhibited the growth of intestinal microbiota of silkworms, observed concurrently with low ROS content and a high activity of antioxidant enzymes (SOD, TPX, CAT). Gene expression associated with the Duox-ROS defense system was detected using RT-qPCR and identified to be low in the AD group and significantly higher in the TM group of silkworms. This study provides a new reference for the future improvement of the artificial diet feeding of silkworm and a systematic indicator for the further study of the relationship between changes in the intestinal environment and intestinal microbiota balance caused by dietary alterations.


Correction to: Update on Devices for Diastolic Dysfunction: Options for a No Option Condition?
In the original publication, the author name "Amit Gupta" was incorrectly spelled as "Ahmit Gupta". The original article has been corrected.


The catalytic domains of Streptococcus mutans glucosyltransferases: a structural analysis.
Streptococcus mutans, found in the human oral cavity, is a significant contributor to the pathogenesis of dental caries. This bacterium expresses three genetically distinct types of glucosyltransferases named GtfB (GTF-I), GtfC (GTF-SI) and GtfD (GTF-S) that play critical roles in the development of dental plaque. The catalytic domains of GtfB, GtfC and GtfD contain conserved active-site residues for the overall enzymatic activity that relate to hydrolytic glycosidic cleavage of sucrose to glucose and fructose, release of fructose and generation of a glycosyl-enzyme intermediate in the reducing end. In a subsequent transglycosylation step, the glucosyl moiety is transferred to the nonreducing end of an acceptor to form a growing glucan polymer chain made up of glucose molecules. It has been proposed that both sucrose breakdown and glucan synthesis occur in the same active site of the catalytic domain, although the active site does not appear to be large enough to accommodate both functions. These three enzymes belong to glycoside hydrolase family 70 (GH70), which shows homology to glycoside hydrolase family 13 (GH13). GtfC synthesizes both soluble and insoluble glucans (α-1,3 and α-1,6 glycosidic linkages), while GtfB and GtfD synthesize only insoluble or soluble glucans, respectively. Here, crystal structures of the catalytic domains of GtfB and GtfD are reported. These structures are compared with previously determined structures of the catalytic domain of GtfC. With this work, apo structures and inhibitor-complex structures with acarbose are now available for the catalytic domains of GtfC and GtfB. The structure of GtfC with maltose allows further identification and comparison of active-site residues. A model of sucrose binding to GtfB is also included. The new structure of the catalytic domain of GtfD affords a structural comparison of the three S. mutans glycosyltransferases. Unfortunately, the catalytic domain of GtfD is not complete since crystallization resulted in the structure of a truncated protein lacking approximately 200 N-terminal residues of domain IV.


A case of COVID-19 with superficial thrombophlebitis caused by an indwelling peripheral venous catheter.
A local hypercoagulable state caused by SARS-CoV-2 and an indwelling peripheral venous catheter can lead to superficial thrombophlebitis. If the venous catheter is no longer needed during treatment for COVID-19 it should be removed promptly.


Congenital aortopulmonary artery fistulas combined with bilateral coronary artery fistulas.
We describe an extremely rare case of "congenital aorto-pulmonary artery fistulas" combined with bilateral coronary artery fistulas associated with clinically significant left-to-right shunt. A multi-detector row computed tomographic scan revealed that tortuous anomalous vessels arising from the aortic arch, left anterior descending coronary artery, diagonal branch, and right coronary artery were connected to the main pulmonary trunk. After surgical intervention, the systemic-to-pulmonary flow ratio nearly normalized from 2.02 to 1.05. We describe the case and speculate as to the embryological pathogenesis of these unique fistulas.


alpha-Crystallin A sequences of Alligator mississippiensis and the lizard Tupinambis teguixin: molecular evolution and reptilian phylogeny.
The amino acid sequences of the eye lens protein alpha-crystallin A from many mammalian and avian species, two frog species, and a dogfish have provided detailed information about the molecular evolution of this protein and allowed some useful inferences about phylogenetic relationships among these species. We now have isolated and sequenced the alpha-crystallins of the American alligator and the common tegu lizard. The reptilian alpha A chains appear to have evolved as slowly as those of other vertebrates, i.e., at two to three amino acid replacements per 100 residues in 100 Myr. The lack of charged replacements and the general types and distribution of replacements also are similar to those in other vertebrate alpha A chains. Maximum-parsimony analyses of the total data set of 67 vertebrate alpha A sequences support the monophyletic origin of alligator, tegu, and birds and favor the grouping of crocodilians and birds as surviving sister groups in the subclass Archosauria.


Enhancement of pipecolic acid production by the expression of multiple lysine cyclodeaminase in the Escherichia coli whole-cell system.
Pipecolic acid, a non-proteinogenic amino acid, is a metabolite in lysine metabolism and a key chiral precursor in local anesthesia and macrolide antibiotics. To replace the environmentally unfriendly chemical production or preparation procedure of pipecolic acid, many biological synthetic routes have been studied for a long time. Among them, synthesis by lysine cyclodeaminase (LCD), encoded by pipA, has several advantages, including stability of enzyme activity and NAD+ self-regeneration. Thus, we selected this enzyme for pipecolic acid biosynthesis in a whole-cell bioconversion. To construct a robust pipecolic acid production system, we investigated important conditions including expression vector, strain, culture conditions, and other reaction parameters. The most important factor was the introduction of multiple pipA genes into the whole-cell system. As a result, we produced 724 mM pipecolic acid (72.4 % conversion), and the productivity was 0.78 g/L/h from 1 M l-lysine after 5 days. This is the highest production reported to date.


Image guidance using two-dimensional illustrations and three-dimensional modeling of donor anatomy during living donor hepatectomy.
For living donor liver transplantation, preoperative imaging is required for the safety of both the donor and the recipient. We previously initiated our image-guidance program using two-dimensional illustrations and three-dimensional modeling in September 2018; herein, we analyzed the resultant changes in the clinical outcomes. Living donors and recipients who underwent liver transplantation between September 2017 and August 2019 were included. Cases with image guidance were compared to those without image guidance regarding the operative outcome, especially bile-duct opening in the graft as well as surgical complications. Among 200 living donor transplantation, 90 transplantations were completed with image guidance. The image-guidance group had a higher rate of laparoscopy (80.9% vs. 97.8%; p < .001) as compared with the group without image guidance. Although there was no difference in the type of bile duct (p = .144), more grafts with single bile-duct openings were found in the image-guidance group (52.7% vs. 80.0%; p = .001). Consequently, achievements in bile-duct openings were superior in the image-guidance group (p = .022). There were no differences in bile leakage, graft failure, or number of deaths during the first month post-transplantation. As we initiated our image-guidance program for living donor liver transplantation, clinical outcomes, especially bile-duct division, were improved relative to before implementation.


Reduced pain sensitivity of episodic pain syndrome model mice carrying a Nav1.9 mutation by ANP-230, a novel sodium channel blocker.
The sodium channel Nav1.9 is expressed in the sensory neurons of small diameter dorsal root ganglia that transmit pain signals, and gain-of-function Nav1.9 mutations have been associated with both painful and painless disorders. We initially determined that some Nav1.9 mutations are responsible for familial episodic pain syndrome observed in the Japanese population. We therefore generated model mice harboring one of the more painful Japanese mutations, R222S, and determined that dorsal root ganglia hyperexcitability was the cause of the associated pain. ANP-230 is a novel non-opioid drug with strong inhibitory effects on Nav1.7, 1.8 and 1.9, and is currently under clinical trials for patients suffering from familial episodic pain syndrome. However, little is known about its mechanism of action and effects on pain sensitivity. In this study, we therefore investigated the inhibitory effects of ANP-230 on the hypersensitivity of Nav1.9 p.R222S mutant model mouse to pain. In behavioral tests, ANP-230 reduced the pain response of the mice, particularly to heat or mechanical stimuli, in a concentration- and time-dependent manner. Furthermore, ANP-230 suppressed the repetitive firing of dorsal root ganglion neurons of these mutant mice. Our results clearly demonstrate that ANP-230 is an effective analgesic for familial episodic pain syndrome resulting from DRG neuron hyperexcitability, and that such analgesic effects are likely to be of clinical significance.


Seasonal characterization of the prokaryotic microbiota of full-scale anaerobic UASB reactors treating domestic sewage in southern Brazil.
Upflow Anaerobic Sludge Blanket (UASB) reactors are alternatives in the anaerobic treatment of sanitary sewage in different parts of the world; however, in temperate environments, they are subject to strong seasonal influence. Understanding the dynamics of the microbial community in these systems is essential to propose operational alternatives, improve projects and increase the quality of treated effluents. In this study, for one year, high-performance sequencing, associated with bioinformatics tools for taxonomic annotation and functional prediction was used to characterize the microbial community present in the sludge of biodigesters on full-scale, treating domestic sewage at ambient temperature. Among the most representative phyla stood out Desulfobacterota (20.21-28.64%), Proteobacteria (7.48-24.90%), Bacteroidota (10.05-18.37%), Caldisericota (9.49-17.20%), and Halobacterota (3.23-6.55%). By performing a Canonical Correspondence Analysis (CCA), Methanolinea was correlated to the efficiency in removing Chemical Oxygen Demand (COD), Bacteroidetes_VadinHA17 to the production of volatile fatty acids (VFAs), and CI75cm.2.12 at temperature. On the other hand, Desulfovibrio, Spirochaetaceae_uncultured, Methanosaeta, Lentimicrobiaceae_unclassified, and ADurb.Bin063-1 were relevant in shaping the microbial community in a co-occurrence network. Diversity analyses showed greater richness and evenness for the colder seasons, possibly, due to the lesser influence of dominant taxa. Among the principal metabolic functions associated with the community, the metabolism of proteins and amino acids stood out (7.74-8.00%), and the genes related to the synthesis of VFAs presented higher relative abundance for the autumn and winter. Despite the differences in diversity and taxonomic composition, no significant changes were observed in the efficiency of the biodigesters.


Cisplatin and carboplatin pharmacokinetics in a pediatric patient with hepatoblastoma receiving peritoneal dialysis.
Cisplatin and carboplatin are frequently used drugs in the treatment of pediatric hepatoblastoma. Dosing guidelines for these drugs in children requiring peritoneal dialysis are lacking. Here, we describe the case of a 3-year-old boy with pre-existing end-stage renal disease on peritoneal dialysis, requiring treatment with cisplatin and carboplatin for hepatoblastoma. Pharmacokinetic data were generated to support clinical dosing decisions, with the aim of adequate exposure and minimal toxicity. In the first chemotherapy cycle, 25% of the standard cisplatin dose and 75% of the carboplatin dose, calculated using the pediatric Calvert formula, were administered. Free platinum concentrations were determined in plasma ultrafiltrate and dialysate samples drawn after administration of cis- and carboplatin. Cisplatin was well tolerated and the observed AUC of cisplatin were 15.3 and 14.3 mg/L h in cycles 1 and 3, respectively. The calculated AUC of carboplatin in cycle 1 (9.8 mg/mL min) exceeded target AUC of 6.5 mg/mL min and toxicity was observed; therefore, the dose was reduced in cycles 2 and 3. The observed AUC in cycles 2 and 3 was 5.4 and 5.7 mg/mL min respectively. Platinum concentrations in the dialysate showed that 3-4% of the total dose of cisplatin and 10-12% of the total dose of carboplatin were excreted via peritoneal dialysis. Chemotherapy enabled extended hemihepatectomy and complete remission was achieved. This report shows that it is feasible to measure AUCs for both drugs and to individualize the dose of these drugs according to the PK results and clinical parameters. Our advice for future cases would be to calculate the starting dose of carboplatin using the (pediatric) Calvert formula, assuming a dialytic clearance of zero, and to adjust the dose if required, based on therapeutic drug monitoring.


Atomic-scale structure relaxation, chemistry and charge distribution of dislocation cores in SrTiO3.
By using the state-of-the-art microscopy and spectroscopy in aberration-corrected scanning transmission electron microscopes, we determine the atomic arrangements, occupancy, elemental distribution, and the electronic structures of dislocation cores in the 10° tilted SrTiO3 bicrystal. We identify that there are two different types of oxygen deficient dislocation cores, i.e., the SrO plane terminated Sr0.82Ti0.85O3-x (Ti3.67+, 0.48 ≤ x ≤ 0.91) and TiO2 plane terminated Sr0.63Ti0.90O3-y (Ti3.60+, 0.57 ≤ y ≤ 1). They have the same Burgers vector of a[100] but different atomic arrangements and chemical properties. Besides the oxygen vacancies, Sr vacancies and rocksalt-like titanium oxide reconstruction are also identified in the dislocation core with TiO2 plane termination. Our atomic-scale study reveals the true atomic structures and chemistry of individual dislocation cores, providing useful insights into understanding the properties of dislocations and grain boundaries.


Acidity-Triggered Transformable Polypeptide Self-Assembly to Initiate Tumor-Specific Biomineralization.
Biomineralization is a normal physiological process that includes nucleation, crystal growth, phase transformation, and orientation evolution. Notably, artificially induced biomineralization in the tumor tissue has emerged as an unconventional yet promising modality for malignancy therapy. However, the modest ion-chelating capabilities of carboxyl-containing biomineralization initiators lead to a deficient blockade, thus compromising antitumor efficacy. Herein, a biomineralization-inducing nanoparticle (BINP) is developed for blockade therapy of osteosarcoma. BINP is composed of dodecylamine-poly((γ-dodecyl-l-glutamate)-co-(l-histidine))-block-poly(l-glutamate-graft-alendronate) and combines a cytomembrane-insertion moiety, a tumor-microenvironment (TME)-responsive component, and an ion-chelating motif. After intravenous injection into osteosarcoma-bearing mice, BINP responds to the acidic TME to expose the dodecyl group on the surface of the expanded nanoparticles, facilitating their cytomembrane insertion. Subsequently, the protruding bisphosphonic acid group triggers continuous ion deposition to construct a mineralized barrier around the tumor, which blocks substance exchange between the tumor and surrounding normal tissues. The BINP-mediated blockade therapy displays tumor inhibition rates of 59.3% and 52.1% for subcutaneous and orthotopic osteosarcomas, respectively, compared with the Control group. In addition, the suppression of osteoclasts by the alendronate moiety alleviates bone dissolution and further inhibits pulmonary metastases. Hence, the BINP-initiated selective biomineralization provides a promising alternative for clinical osteosarcoma therapy.


Does a short cessation of HRT decrease mammographic density?
Hormone replacement therapy (HRT) is known to increase breast density, thus decreasing the sensitivity of cancer screening by mammography. Some authors recommend short cessation of HRT before mammography, but evidence showing the effect of such short cessation is limited. The purpose of this study is to examine whether a short cessation of HRT changes mammographic density. Forty-eight women taking HRT agreed to have mammograms taken before and after stopping HRT for 4 weeks. Mammographic density was measured by Wolfe's four-point classification, six-categorical visual scale and two different computer methods (interactive-thresholding and SMF). Density values of mammography before and after the cessation of HRT were compared using Wilcoxon signed-rank test for categorical variables and paired t-test for continuous variables. Changes in breast pain and tenderness during mammography, radiation dose, compression force, and breast thickness were also recorded. No significant changes in mammographic density were observed by either visual or computer methods. There were no significant changes in breast pain or in tenderness on mammograms before and after the month's cessation of HRT. Radiographic measurements were not significantly altered by the 4-week cessation of HRT. In this screening population, a 4-week cessation of HRT before mammograms did not significantly alter mammographic density.


Dioxin activation of CYP1A5 promoter/enhancer regions from two avian species, common cormorant (Phalacrocorax carbo) and chicken (Gallus gallus): association with aryl hydrocarbon receptor 1 and 2 isoforms.
The present study focuses on the molecular mechanism and interspecies differences in susceptibility of avian aryl hydrocarbon receptor (AHR)-cytochrome P4501A (CYP1A) signaling pathway. By the cloning of 5'-flanking regions of CYP1A5 gene from common cormorant (Phalacrocorax carbo) and chicken (Gallus gallus), seven putative xenobiotic response elements (XREs) were identified within 2.7 kb upstream region of common cormorant CYP1A5 (ccCYP1A5), and six XREs were found within 0.9 kb of chicken CYP1A5 (ckCYP1A5). Analysis of sequential deletion and mutagenesis of the binding sites in avian CYP1A5 genes by in vitro reporter gene assays revealed that two XREs at -613 bp and -1585 bp in ccCYP1A5, and one XRE at -262 bp in ckCYP1A5 conferred TCDD-responsiveness. The binding of AHR1 with AHR nuclear translocator 1 (ARNT1) to the functional XRE in a TCDD-dependent manner was verified with gel shift assays, suggesting that avian CYP1A5 is induced by TCDD through AHR1/ARNT1 signaling pathway as well as mammalian CYP1A1 but through a distinct pathway from mammalian CYP1A2, an ortholog of the CYP1A5. TCDD-EC(50) for the transcriptional activity in both cormorant AHR1- and AHR2-ccCYP1A5 reporter construct was 10-fold higher than that in chicken AHR1-ckCYP1A5 reporter construct. In contrast, chicken AHR2 showed no TCDD-dependent response. The TCDD-EC(50) for CYP1A5 transactivation was altered by switching AHR1 between the two avian species, irrespective of the species from which the regulatory region of CYP1A5 gene originates. Therefore, the structural difference in AHR, not the CYP1A5 regulatory region may be a major factor to account for the dioxin susceptibility in avian species.


Structure determination of a novel uronic acid residue isolated from the exopolysaccharide produced by a bacterium originating from deep sea hydrothermal vents.
The exopolysaccharide produced by the bacterium Alteromonas sp. strain 1644 originating from deep sea hydrothermal vents was shown to contain a novel glucuronic acid derivatives: 3-O-[(R)-1-carboxyethyl]-D-glucuronic acid. The structure of this compound was established on the basis of mass spectrometric data, methylation analysis, preparation of derivatives, and chemical synthesis of references compounds.


The Use of Cone-Beam Computed Tomography in Management of Patients Requiring Dental Implants: An American Academy of Periodontology Best Evidence Review.
Application of cone-beam computed tomography (CBCT) has grown exponentially across dentistry with a clear impact in implant dentistry. This review aims at providing the scientific context to understand if CBCT imaging should become the standard of care for patients requiring dental implants. A literature search for CBCT applications in implant dentistry was performed using the PubMed database that included studies published between January 1, 2000, and June 24, 2017. Of 559 citations identified and manually screened, 161 were selected as suitable for the purpose of the review. The selected studies belonged to three distinct categories: 1) diagnosis and treatment outcome assessment, 2) implant treatment planning, and 3) anatomic characterization. The current available literature reflects an increased optimization of emerging CBCT imaging protocols and further highlights its diverse applications for dental implant therapy. This technology continues to be considered an advanced point-of-care imaging modality and should be used selectively as an adjunct to two-dimensional dental radiography. As with other ionizing radiation imaging modalities, CBCT imaging should be used only when the potential benefits to the patient outweigh the risks. Dental health care professionals should consider CBCT imaging only when they expect the diagnostic information yielded will lead to better patient care, enhanced patient safety, and ultimately facilitate a more predictable, optimal treatment outcome.


Investigation of possible health effects of community exposure to fermenting wood chips.
We conducted a case-control study of emergency room (ER) patients to evaluate whether asthma is caused by living near a wood-chip fueled power plant that released wood-chip fermentation products. Only eight (29 per cent) of 28 asthma patients seen in the ER during an 11-week period lived within 1.5 miles of the plant compared with 18 (34 per cent) of 54 control patients matched for severity of diagnosis and seen during the same period (Mantel-Haenszel odds ratio controlling for age = 0.96).


Timing for orthotopic liver transplantation in children with biliary atresia: a single-center experience.
Biliary atresia is the most common indication for orthotopic liver transplantation (OLT) in childhood. The purpose of this study was to determine predictive prognostic factors for children with biliary atresia related to the timing for OLT within 15 months after hepatoportoenterostomy (HPE). We retrospectively analyzed the medical records of 25 children (7 boys and 18 girls) who underwent HPE because of biliary atresia between January 1990 and December 2005 at our center. Data examined included age and pathologic findings at HPE, Pediatric End-Stage Liver Disease score at first admission, whether phototherapy was given, liver function test results and total bilirubin level before and 30 days after HPE, and number of cholangitis events. Twelve children were alive with their native liver, 8 had undergone living donor OLT (all children alive), and 5 had died without OLT. Five- and 10-year survival rates without OLT after HPE were 47.4% and 26.3%, respectively. At univariate analysis, the predictive prognostic factors for children with biliary atresia were total bilirubin level at 30 days after HPE and Pediatric End-Stage Liver Disease score before HPE. At multivariate analysis, the only prognostic factor was total bilirubin level at 30 days after HPE. In this study, the predictive prognostic factor was total bilirubin level at 30 days after HPE. Orthotopic liver transplantation within 15 months after HPE is needed in children with biliary atresia with a high total bilirubin level at 30 days after HPE.


The effect of ornidazole on fertility and epididymal sperm function in rats.
A comprehensive study of male fertility and sperm production and function was performed in 20 control and 20 rats treated with ornidazole, a compound with trichomonacidal activity. Rats were treated for 4 weeks at dosages of 0 (control) and 400 mg/kg/day of ornidazole during which fertility was assessed by weekly matings. Testicular sperm production and epididymal sperm function were assessed in one-half of the rats while the reversibility of effects after a 2-week recovery period was assessed in the remaining half. Male rats treated with ornidazole were infertile during the second week of treatment. After 4 weeks of treatment, testicular and epididymal weights, testicular spermatid counts, epididymal sperm reserves, sperm morphology, and sperm viability were similar in treated and control rats. A quantitative assessment of epididymal sperm motility using a dark-field photomicroscope with a stroboscopic light source revealed that ornidazole markedly inhibited sperm motility. Although the percentage of nonmotile sperm was not substantially increased in treated rats, the vigor of tail movement was markedly decreased which resulted in decreased sperm velocity. Restoration of fertility and normal sperm motility and velocity were observed in the group of recovery rats assessed 2 weeks after the cessation of ornidazole treatment. It is concluded that ornidazole, at a high dosage of 400 mg/kg/day, produces infertility in male rats by inhibiting epididymal sperm motility in terms of decreased sperm velocity. These effects are rapidly reversible after the cessation of treatment.


Potential roles of bone morphogenetic protein-9 in glucose and lipid homeostasis.
Bone morphogenetic protein-9 (BMP-9) is a novel cytokine which is cloned from the fetal mouse liver cDNA library and belongs to the member of the transforming growth factor-β (TGF-β) superfamily. BMP-9 is mainly secreted by the liver and exerts a variety of physiological functions. In this review, we present the latest knowledge on the biochemistry of BMP-9 and its role in glucose metabolism and lipid homeostasis. We introduced the expression site, structure, synthesis, and secretion of BMP-9, as well as BMP-9 signaling pathway. We also discuss the effects of BMP-9 on glucose metabolism and lipid metabolism in different organs. BMP-9 can regulate glucose and lipid homeostasis in the body by inhibiting liver gluconeogenesis, transforming white adipose tissue to brown adipose tissue, promoting muscle glycogen synthesis, increasing the uptake and utilization of glucose by muscle tissue, increasing liver and adipose tissue insulin sensitivity, promoting insulin synthesis and secretion, inhibiting liver lipid deposition, and playing a leptin-like role. Finally, through the results of animal intervention studies and human clinical studies in the review, we deeply understand the association of BMP-9 with obesity, insulin resistance (IR), type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD), which provides new ideas for the prevention and treatment of diseases.


Effect of pretreatment with bronchodilator drugs on in vitro responsiveness of guinea pig lung adenylate cyclase.
Pretreatment of guinea pigs with 5 microgram/kg isoprenaline or 10 microgram/kg salbutamol s.c. thrice daily for 7 days reduced the responsiveness of lung slice and tracheal ring adenylate cyclase to isoprenaline, but not to prostaglandin E1. Pretreatment of guinea pigs with isoprenaline also reduced the sensitivity of tracheal smooth muscle strip adenylate cyclase to isoprenaline. Cross-tolerance developed to noradrenaline in lung slices obtained from guinea pigs pretreated with isoprenaline. Propranolol blocked the response of lung slice adenylate cyclase of control and isoprenaline-pretreated animals to approximately the same degree. The presence of phentolamine in the incubation medium did not affect the reduced sensitivity to isoprenaline. Possible mechanisms of development of tolerance to sympathomimetic bronchodilator drugs are discussed.


Use of albumin fusion technology to prolong the half-life of recombinant factor VIIa.
A significant proportion of patients with haemophilia A develop inhibitors to administered factor VIII (FVIII) and require therapy with bypassing agents such as activated factor VII (FVIIa) or activated prothrombin complex concentrates. NovoSeven is a commercially available recombinant FVIIa (rFVIIa) with a very short half-life of approximately 2.4 hours. As a result, patients generally require multiple, frequent infusions for the management of bleeding episodes. Thus, there is growing interest in extending the circulating half-life of coagulation factors through the use of innovative drug delivery and formulation technologies. One such approach uses albumin fusion technology in which human albumin is genetically fused to the C-terminus of rFVIIa via a flexible glycine serine linker. The properties of this rFVIIa fusion protein (rVIIa-FP) have recently been examined in pre-clinical studies. Results from these investigations demonstrate the feasibility of this approach, which successfully extended the half-life and biological activity of rFVIIa without compromising haemostatic efficacy. These data suggest that rVIIa-FP may be a promising therapy for the treatment of haemophilia patients with inhibitors and warrants further investigation in clinical trials.


Fibrinogen: agreement of experimental and calculated hydrodynamic data with electron-microscopic models.
There is no general agreement on the size and shape of the fibrinogen molecule. We have studied the diffusion of the fibrinogen in solution by means of dynamic light scattering, nanosecond fluorescence depolarization and analytical ultracentrifugation. The results obtained under physiological concentration, pH an ionic strength are DT = 2.0 X 10(7) cm2sec-1, DR perpendicular = 40'000 sec 1. Nanosecond fluorescence depolarization yielded DR parallel = 1.6 x 10(6) sec-1. Tentatively this value is interpreted as DR parallel, namely rotational diffusion about the major axis of the molecule. The sedimentation coefficient is 8.1 S. The hydrodynamic parameters derived from our measurements were compared with those calculated on the basis of the models proposed by Hall and Slayter, Hudry-Clergeon and Marguerie et al., Bachmann and Lederer, and Köppel. The agreement is poor even if the degree of hydration is varied within wide limits. However, satisfactory agreement can be achieved by assuming a flexible molecule of about 900 A length corresponding to two end-to-end bound trinodular structures of the Hall and Slayter type, with a nodule diameter of about 45 A. Experimental evidence indicates that the discrepancies between the different models might be due to different techniques of sample preparation leading to different conformations of the molecule.


Vasodilation increases the threshold for bupivacaine-induced convulsions in rats.
Bupivacaine affects the vascular resistance by peripheral and central nervous system (CNS) mechanisms. As vasoconstrictors increase the CNS toxicity of IV bupivacaine, vasodilators may decrease its CNS toxicity. We examined the hypothesis that vasodilators decrease the CNS toxicity of bupivacaine in awake, spontaneously breathing rats. Male Sprague-Dawley rats were randomly divided into control (C), nicardipine (N), and phentolamine (P) groups (n = 12 in each group). Racemic bupivacaine was administered IV at 1 mg/kg/min until tonic/clonic convulsions occurred. Saline, nicardipine (0.4 microg/min), and phentolamine (10 microg/min within 5 min, 50 microg/min thereafter) were simultaneously administered with bupivacaine in groups C, N, and P, respectively. Mean arterial blood pressure was significantly increased by infusion of bupivacaine in group C and was maintained at baseline levels before the onset of convulsions in groups N and P. The convulsive dose of bupivacaine in group C was 5.8 +/- 1.5 mg/kg, but was significantly larger in groups N and P (7.6 +/- 1.5 and 8.1 +/- 1.1 mg/kg, P = 0.02 and 0.001, respectively). However, there were no differences in total or protein-unbound plasma concentration of bupivacaine or in concentration of bupivacaine in the brain at the onset of convulsions among the 3 groups. We conclude that nicardipine and phentolamine increase the cumulative dose but do not affect the threshold plasma or brain concentrations required for bupivacaine-induced convulsions. Bupivacaine, a long-acting local anesthetic, induces central nervous system toxicity when its plasma concentration is increased. Nicardipine and phentolamine increased the cumulative dose but did not affect the threshold plasma concentrations, required for bupivacaine-induced convulsions, suggesting that both nicardipine and phentolamine inhibited the increase in the plasma concentration of bupivacaine by inducing peripheral vasodilation.


Patterned bruising indicating a complete renal artery transection in a fatal occupational accident.
Blunt renal artery injury (BRAI) is a rare finding with incidence ranging from 0.05% to 0.08% among blunt abdominal trauma patients. BRAI occurs in 1% to 4% of patients with renal injury, and the most common cause is motor vehicle accidents. An unusual case of BRAI in a 47-year-old man at work is reported. The victim accidentally fell from a scaffold (approximately 3 m in height). He was transported to the hospital where he was intubated, but he died after 30 min despite the cardio-pulmonary resuscitation. Surveillance cameras showed the man falling from the scaffold, but his impact with the ground was not captured. At autopsy, except for an oval bruise on the left hypochondrium, no external injury was found. The same mark was noticed on the shirt worn by the victim. Bilateral ribs fractures were found. The abdominal cavity was filled with 2 l of fresh blood and clots as a consequence of a complete transection of the left renal artery. Investigation of the workplace revealed a partial footprint on the external side of the scaffold, matching shoes worn by the victim. On the ground, a metallic pedestrian gate with a 1 m high post was found placed just below the scaffold. It was concluded that the man hit the gate's post as intermediate impact after the fall, which caused the oval bruise, ribs fractures, and the rupture of the left renal artery without injury of the internal organs.


High diversity of fungi may mitigate the impact of pollution on plant litter decomposition in streams.
We investigated how a community of microbial decomposers adapted to a reference site responds to a sudden decrease in the water quality. For that, we assessed the activity and diversity of fungi and bacteria on decomposing leaves that were transplanted from a reference (E1) to a polluted site (E2), and results were compared to those from decomposing leaves either at E1 or E2. The two sites had contrasting concentrations of organic and inorganic nutrients and heavy metals in the stream water. At E2, leaf decomposition rates, fungal biomass, and sporulation were reduced, while bacterial biomass was stimulated. Fungal diversity was four times lower at the polluted site. The structure of fungal community on leaves decomposing at E2 significantly differed from that decomposing at E1, as indicated by the principal response curves analysis. Articulospora tetracladia, Anguillospora filiformis, and Lunulospora curvula were dominant species on leaves decomposing at E1 and were the most negatively affected by the transfer to the polluted site. The transfer of leaves colonized at the reference site to the polluted site reduced fungal diversity and sporulation but not fungal biomass and leaf decomposition. Overall, results suggest that the high diversity on leaves from the upstream site might have mitigated the impact of anthropogenic stress on microbial decomposition of leaves transplanted to the polluted site.


Smooth muscle cell hypertrophy and hyperplasia in the rat detrusor after short-time infravesical outflow obstruction.
Infravesical outflow obstruction of a duration of 3 days, 10 days and 6 weeks was induced in female rats by a standardized degree of urethral obstruction. A striking ability of the detrusor to respond to an acute obstruction with both smooth muscle cell hypertrophy and hyperplasia leading to an approximately 10-fold increase of the total muscle mass of the bladder wall after 6 weeks of obstruction was found. The maximum relative growth rate was greatest in the bladders subjected to obstruction for only 3 days, and this was also reflected by the concentrations of ornithine decarboxylase and the polyamines spermidine and spermine. The total amount of DNA in the detrusor was already significantly increased after 3 days, while a 9-fold increase was observed in the group subjected to obstruction for 6 weeks. At this time the smooth muscle cell nucleus volume also showed a considerable increase, and a comparison of the nucleus density and the DNA concentration suggested an increased mean DNA content per muscle cell nucleus. The concentration of RNA in the detrusor had already increased significantly after 3 days and also remained so after 10 days and 6 weeks of obstruction, a finding that coincided with the abundant appearance of nucleoli seen at electron microscopic investigation. The previously reported decreased ability to pressure production at small volumes in the rat urinary bladder subjected to an acute infravesical outflow obstruction might thus, at least in part, be due to changed contractile properties of the hypertrophic cells, and/or to an inefficient incorporation of the newly formed smooth muscle cells.


An Unusual Presentation of Wegener's Granulomatosis with Otologic Symptoms and Unilateral Parotid Gland Enlargement.
Wegener's granulomatosis is an autoimmune disease affecting the lungs, kidneys and upper respiratory organs. Major salivary gland enlargement is a rare presenting symptom. We are reporting a rare case of Wegener's granulomatosis presenting with pain in right ear with moderate hearing loss and unilateral painless parotid gland enlargement.


PTEN augments staurosporine-induced apoptosis in PTEN-null Ishikawa cells by downregulating PI3K/Akt signaling pathway.
Staurosporine is a potent apoptosis inducer, but its mechanism remains to be clarified. We investigated the involvement of PTEN in staurosporine-induced apoptosis. Ishikawa cells, from an endometrial carcinoma cell line, expressed a high amount of PTEN mRNA but did not express the PTEN protein because of protein truncations. We isolated clones expressing the steady-state level of the PTEN protein from PTEN-null Ishikawa cells by transfection. The obtained clones showed reduced proliferative activity and reduced anchorage-independent cell growth with the augmented p27(Kip1). These cell lines were sensitized to apoptosis by staurosporine. A low concentration of UCN-01 did not affect apoptosis, but a high concentration augmented apoptosis in the PTEN-expressing clone. Alpha-sphingosine and H-7 did not affect apoptosis in these cell lines. PI3K inhibition augmented staurosporine-induced apoptosis in the parental cell line, but not in the PTEN-expressing clone. In the clone, phosho-Akt/PKB and phospho-Bad (Ser-136) were downregulated. Staurosporine reduced the levels of phospho-Akt/PKB and phospho-Bad (Ser-136) in all the cell lines, but the reduction was most significant in the PTEN-expressing clone. These results suggest that inhibition of the PI3K/Akt/PKB signaling pathway might be associated with staurosporine-induced apoptosis in Ishikawa cells.


Cell adhesion regulates melanoma specific differentiation and interactions with the 3' region of the tyrosinase gene.
Decreased attachment to substratum has now been found to increase melanosome formation and cell-cell interaction in B16 melanoma. Since melanosome formation involves tyrosinase gene expression, we assayed for differential RNA expression by hybridization with probes from the distal ends of this gene, detecting unequal reactivity only with the 3' end probe. The same DNA showed binding of 2 nuclear proteins of 50 and 60 kd in unanchored cells, in contrast with a decreased binding of the 60 kd species, in nuclear extracts from attached cells. No comparable differences were detected with a gamma-actin DNA of identical length, suggesting that the changes observed are sequence-specific. Our studies suggest that the adhesion-mediated modulation of pigmentation in B16 melanoma correlates with differential macromolecular interactions with the 3' end of the tyrosinase gene.


Environmental rhythms orchestrate neural activity at multiple stages of processing during memory encoding: Evidence from event-related potentials.
Accumulating evidence suggests that rhythmic temporal structures in the environment influence memory formation. For example, stimuli that appear in synchrony with the beat of background, environmental rhythms are better remembered than stimuli that appear out-of-synchrony with the beat. This rhythmic modulation of memory has been linked to entrained neural oscillations which are proposed to act as a mechanism of selective attention that prioritize processing of events that coincide with the beat. However, it is currently unclear whether rhythm influences memory formation by influencing early (sensory) or late (post-perceptual) processing of stimuli. The current study used stimulus-locked event-related potentials (ERPs) to investigate the locus of stimulus processing at which rhythm temporal cues operate in the service of memory formation. Participants viewed a series of visual objects that either appeared in-synchrony or out-of-synchrony with the beat of background music and made a semantic classification (living/non-living) for each object. Participants' memory for the objects was then tested (in silence). The timing of stimulus presentation during encoding (in-synchrony or out-of-synchrony with the background beat) influenced later ERPs associated with post-perceptual selection and orienting attention in time rather than earlier ERPs associated with sensory processing. The magnitude of post-perceptual ERPs also differed according to whether or not participants demonstrated a mnemonic benefit for in-synchrony compared to out-of-synchrony stimuli, and was related to the magnitude of the rhythmic modulation of memory performance across participants. These results support two prominent theories in the field, the Dynamic Attending Theory and the Oscillation Selection Hypothesis, which propose that neural responses to rhythm act as a core mechanism of selective attention that optimize processing at specific moments in time. Furthermore, they reveal that in addition to acting as a mechanism of early attentional selection, rhythm influences later, post-perceptual cognitive processes as events are transformed into memory.


Feasibility of Prehospital Rapid Sequence Intubation in the Cabin of an AW169 Helicopter.
Prehospital rapid sequence intubation (RSI) is an important aspect of prehospital care for helicopter emergency medical services (HEMS). This study examines the feasibility of in-aircraft (aircraft on the ground) RSI in different simulated settings. Using an AW169 aircraft cabin simulator at Air Ambulance Kent Surrey Sussex, 3 clinical scenarios were devised. All required RSI in a "can intubate, can ventilate" (easy variant) and a "can't intubate, can't ventilate" scenario (difficult variant). Doctor-paramedic HEMS teams were video recorded, and elapsed times for prespecified end points were analyzed. Endotracheal intubation (ETI) was achieved fastest outside the simulator for the easy variant (median = 231 seconds, interquartile range = 28 seconds). Time to ETI was not significantly longer for in-aircraft RSI compared with RSI outside the aircraft, both in the easy (p = .14) and difficult variant (p = .50). Wearing helmets with noise distraction did not impact the time to intubation when compared with standard in-aircraft RSI, both in the easy (p = .28) and difficult variant (p = .24). In-aircraft, on-the-ground RSI had no significant impact on the time to successful completion of ETI. Future studies should prospectively examine in-cabin RSI and explore the possibilities of in-flight RSI in civilian HEMS services.


Relationship between red blood cell aggregation and dextran molecular mass.
The aim of this study was to investigate the aggregation of red blood cells (RBCs) suspended in dextran solution at various levels of molecular mass. Dextran solutions at molecular mass 40, 70, 100 and 500 kDa at concentration from 2 to 5 g/dL were used to suspend the RBCs. The radius and velocity of sedimenting RBC aggregates were investigated using image analysis. The radius and sedimentation velocity of aggregates increased initially, then decreased after achieving maxima. The maximal velocity of RBC aggregates showed a bell-shaped dependence on dextran molecular mass and concentration, whereas maximal radius showed monotonic increase with both factors. Difference between aggregate and solution density was estimated using aggregate radius and sedimentation velocity and dextran solution viscosity, and was consistent across most molecular mass and concentration levels. This allowed to calculate the porosity of aggregates and to show that it monotonically decreased with the increase in the solution density, caused by the increase in the dextran concentration. The results provide insight into the RBC aggregation process in solutions of proteins of different size, reflecting various pathological conditions. The currently reported data can be potentially applied to specific pathophysiological conditions giving an interpretation that is not yet fully discussed in the literature.


Collaborative technology use by healthcare teams.
This paper reviews the literature on the use of collaborative technologies by healthcare teams between 1980 and 2003. Multiple databases were searched with explicit inclusion criteria that yielded 17 conceptual and empirical papers. The discussions of these literatures centered on the individual, team, and technological dimensions of collaborative technology use within healthcare teams. Results show that collaborative healthcare technologies can have positive effects on team work processes at both the individual and group level. The limited number of research studies accentuates the need for additional research in this area. Future research should focus on defining team tasks; determining which type of groupware works for a particular health setting; and exploring the effects of groupware on patient care delivery and the organization. Without research in these areas, it will be difficult to harness the full advantages of using groupware technologies by collaborative healthcare teams.


Serum Serotonin as a Biomarker of the Efficacy of PAP-Therapy in Sleep Apnea Syndrome.
Serum serotonin levels were determined by HPLC in 30 patients with diagnosed obstructive sleep apnea syndrome before and after 3-month course of PAP-therapy and in 14 subjects without obstructive sleep apnea symptoms. It was found that elimination of hypoxic conditions was associated with an increase in serotonin level. The results demonstrate the effectiveness of PAP-therapy during sleep and allow assessing the role of serotonin as a potential biomarker of intermittent hypoxia during sleep.


Detection of isolated protein-bound metal ions by single-particle cryo-STEM.
Metal ions play essential roles in many aspects of biological chemistry. Detecting their presence and location in proteins and cells is important for understanding biological function. Conventional structural methods such as X-ray crystallography and cryo-transmission electron microscopy can identify metal atoms on protein only if the protein structure is solved to atomic resolution. We demonstrate here the detection of isolated atoms of Zn and Fe on ferritin, using cryogenic annular dark-field scanning transmission electron microscopy (cryo-STEM) coupled with single-particle 3D reconstructions. Zn atoms are found in a pattern that matches precisely their location at the ferroxidase sites determined earlier by X-ray crystallography. By contrast, the Fe distribution is smeared along an arc corresponding to the proposed path from the ferroxidase sites to the mineral nucleation sites along the twofold axes. In this case the single-particle reconstruction is interpreted as a probability distribution function based on the average of individual locations. These results establish conditions for detection of isolated metal atoms in the broader context of electron cryo-microscopy and tomography.


Aquaporin-4 water channel oligomers are associated with the transverse tubules of skeletal myofibers.
Transverse (T) tubules comprise a tortuous network inside the skeletal myofibers enclosing a distinct osmotic environment. Here we have examined whether the T tubules contain aquaporin type 4 (AQP4) water channels to mediate rapid transmembrane water flow. Separation of T tubular and sarcolemmal membranes by sucrose density gradient centrifugation revealed that two main isoforms of AQP4, namely M23 and M1, were present in both membrane fractions. Compatible with this, expression of fluorescent Venus-AQP4.M23 in rat muscle showed the protein both in the T tubules and at the sarcolemma. Blue-Native polyacrylamide gel electrophoresis showed that higher order oligomers typical to the AQP4 water channel were present in both membrane compartments. Interestingly, α-syntrophin that mediates binding of AQP4 to the sarcolemmal dystrophin glycoprotein complex was also present in the T tubule fraction. Deletion of the syntrophin-binding sequence of AQP4 increased its mobile fraction at the sarcolemma but not in the T tubules. Taken together, our results strongly suggest that both the sarcolemma and the T tubules harbor higher order oligomers of the AQP4 water channel but the interactions with adjacent macromolecules are different.


Optimization of kVp and mAs for pediatric low-dose simulated abdominal CT: is it best to base parameter selection on object circumference?
The objective of our study was to determine the effect of mAs and kVp reduction on pediatric phantoms based on patient circumference to optimize dose reduction and maintain image quality for abdominal CT. Three polymethylmethacrylate right cylindric CT dose index (CTDI) phantoms with diameters of 10, 16, and 32 cm simulated the abdomen of an infant, child, and adolescent, respectively. Using a National Institute of Standards & Technology ion chamber and Victoreen 660 electrometer, doses at centerline were recorded on a 16-MDCT scanner. Measurements were obtained in incremental steps from 50 to 400 mAs and from 80 to 140 kVp. Noise was calibrated to clinical images through a calibration factor. For phantoms of all circumferences, doses increased linearly with an increase in mAs and by the power function of kVp(n) for increases in kVp. There was an associated decrease in noise for all circumferences and a sharp decrease at lower doses with a plateau at higher doses. Using a noise threshold of 20 HU and a dose threshold of 2.5 cGy, a range of imaging parameters was established for each circumference from which technique optimization curves were created to determine optimal mAs and kVp pairs. The mean measured dose was 2.435 ± 0.019 cGy. The mean measured noise was 29.35 ± 1.45 HU. For pediatric CT, the most accurate way to strike the balance between image quality and radiation dose is to adjust dose to abdominal circumference, not body weight or age. Our data support the use of technique optimization curves to optimize kVp and mAs.


Interplay between membrane curvature and the actin cytoskeleton.
An intimate interplay of the plasma membrane with curvature-sensing and curvature-inducing proteins would allow for defining specific sites or nanodomains of action at the plasma membrane, for example, for protrusion, invagination, and polarization. In addition, such connections are predestined to ensure spatial and temporal order and sequences. The combined forces of membrane shapers and the cortical actin cytoskeleton might hereby in particular be required to overcome the strong resistance against membrane rearrangements in case of high plasma membrane tension or cellular turgor. Interestingly, also the opposite might be necessary, the inhibition of both membrane shapers and cytoskeletal reinforcement structures to relieve membrane tension to protect cells from membrane damage and rupturing during mechanical stress. In this review article, we discuss recent conceptual advances enlightening the interplay of plasma membrane curvature and the cortical actin cytoskeleton during endocytosis, modulations of membrane tensions, and the shaping of entire cells.


Significance of new lung infiltrates in outpatients after lung and heart-lung transplantation.
Infection and rejection represent major complications following lung transplantation and are often associated with pulmonary infiltrates. The differential diagnosis of these infiltrates depends on their timing after transplantation. The aim of this study was to characterize lung transplant recipients (LTR) presenting with new pulmonary infiltrates. A retrospective analysis of all LTR and heart-lung transplant recipients attending outpatient follow-up at our institution between September 1, 2006 and October 14, 2011 was performed. All patients presenting with new pulmonary infiltrates on chest x-ray who underwent bronchoscopy were included. A total of 913 patients accounted for 13,156 attendances, with 3,912 bronchoscopies being performed. Seventy-eight patients (9%) exhibited new pulmonary infiltrates and proceeded to bronchoscopy. Infiltrates occurred at a median 15 (interquartile range [IQR] 5-39) months after transplantation. Forty-eight patients (62%) were male, and median patient age was 47 (IQR 29-57) years. Subsequent investigation revealed pneumonia to be the underlying cause in 63 patients (81%). In the remaining patients, chronic lung allograft dysfunction (CLAD) was responsible in 6 (8%), acute rejection in 5 (6%), and toxic pneumonitis in 4 (5%) patients. Overall 1-year survival in LTR presenting with new infiltrates was 97%, compared with 96% for all LTR attending our Outpatient Department. New pulmonary infiltrates occurring after the first month in LTR are most likely due to infection. Through prompt diagnosis and treatment, early mortality appears unaffected. Late mortality remains attributable to CLAD.


Proteomic approaches in circadian biology.
Circadian clocks are endogenous oscillators that drive the rhythmic expression of a broad array of genes that orchestrate metabolism and physiology. Recent evidence indicates that posttranscriptional and posttranslational mechanisms play essential roles in modulating circadian gene expression, particularly for the molecular mechanism of the clock. In contrast to genetic technologies that have long been used to study circadian biology, proteomic approaches have so far been limited and, if applied at all, have used two-dimensional gel electrophoresis (2-DE). Here, we review the proteomics approaches applied to date in the circadian field, and we also discuss the exciting potential of using cutting-edge proteomics technology in circadian biology. Large-scale, quantitative protein abundance measurements will help to understand to what extent the circadian clock drives system wide rhythms of protein abundance downstream of transcription regulation.


Intracranial pressure elevation after ischemic stroke in rats: cerebral edema is not the only cause, and short-duration mild hypothermia is a highly effective preventive therapy.
Correction to: Journal of Cerebral Blood Flow & Metabolism (2015) 35, 592–600; doi:10.1038/jcbfm.2014.230; published online 17 December 2014. Following the publication of this article, the authors noticed the following error: The Results section of the article contains a typographical error under subheading 'Study III-Effect of Mild Hypothermia, Hematoxylin and Eosin Edema'. . The edema volumes of '3.1±0.65 mm3 versus 27.9±6.5 mm3' should read '0.7±1.2 mm3 versus 6.5 ± 9.2 mm3.'


Expression of cathelicidin in recurrent throat infection.
Epithelial cells can be called the first line of a defense barrier to microorganisms by the innate immune system. The antimicrobial peptides are the major participants of this system. Cathelicidins are a family of peptides thought to provide an innate defensive barrier against a variety of potential microbial pathogens. To evaluate the expression of the cathelicidin in recurrent throat infection. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical staining were performed for 10 palatine tonsil tissues with hypertrophy and 10 palatine tonsil tissues with recurrent throat infection. Cathelicidin mRNA transcripts were detected in recurrent throat infection. The expression levels of cathelicidin mRNA in recurrent throat infection was significantly higher compared with those in hypertrophic tonsils. Cathelicidin protein was localized on the tonsillar surface epithelium and inflammatory cells in the tonsillar crypt of recurrent throat infection patients. These results suggest that cathelicidin is one of antimicrobial peptides in the human palatine tonsils, and that cathelicidin may also play an important role in innate host defense of human tonsils.


Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex.
The glial cell line-derived neurotrophic factor (GDNF) ligands (GDNF, Neurturin [NTN], and Persephin [PSP]) signal through a multicomponent receptor system composed of a high-affinity binding component (GFRalpha1-GFRalpha4) and a common signaling component (RET). Here, we report the identification of Artemin, a novel member of the GDNF family, and demonstrate that it is the ligand for the former orphan receptor GFRalpha3-RET. Artemin is a survival factor for sensory and sympathetic neurons in culture, and its expression pattern suggests that it also influences these neurons in vivo. Artemin can also activate the GFRalpha1-RET complex and supports the survival of dopaminergic midbrain neurons in culture, indicating that like GDNF (GFRalpha1-RET) and NTN (GFRalpha2-RET), Artemin has a preferred receptor (GFRalpha3-RET) but that alternative receptor interactions also occur.


Hb F in sickle cell anemia.
We have reviewed the methodology for an accurate quantitation of Hb F in the blood of patients with sickle cell anemia, values observed in hundreds of patients of different (racial or ethnic) backgrounds and with differences in severity of the disease, and the various factors that affect the level of Hb F. The latter include sex, age, genetic background or chromosomal haplotypes, variations in the sequences of the locus control region(s) 5' to the epsilon-globin gene, and the presence of an alpha chain deficiency or alpha-thalassemia. Finally, a few remarks about agents effective in increasing the in vivo Hb F synthesis are also included.


Calcium carbonate deposits and microbial assemblages on microplastics in oligotrophic freshwaters.
Microplastics are solid polymer particles with a wide variety of surface properties, found in most waterbodies, and known as carriers of distinct microbial communities affecting the fate of the particles in the environment. Little is known about the formation of mineral deposits on microplastics and how these deposits connect to microbial assemblages and affect the physicochemical properties of the particles. In addition, most of the available research on this topic is based on large microplastics with sizes between 100 μm and up to 5 mm, rather than the small microplastics often found in drinking water sources. To narrow this gap in our understanding of environmental effects on small microplastics, two types of small microplastics made of two distinct polymers, poly(methyl methacrylate) (PMMA) and poly(tetrafluoroethylene) (PTFE) with sizes ranging from 15 to 150 μm, were incubated for six months in unprocessed and processed drinking water with increasing ionic concentration to allow for the formation of mineral deposits and microbial assemblages. Spatially resolved analysis with fluorescent in situ hybridization and confocal Raman microscopic imaging revealed deposits of calcium carbonates and scattered microbial assemblages on all microplastics, with structure, extend, and microbial association with the carbonates depending on the respective microplastic. Notably, PTFE floatation was overcome after three months in unprocessed drinking water but remained unchanged in processed drinking water, whereas PMMA appeared unaffected, indicating that the fate of microplastics in the environment may depend on polymer type and the encountered aquatic conditions forming mineral and microbial attachments to the particle surface.


Inhibition of acetylcholine outflow from guinea-pig cerebral cortex following locus coeruleus stimulation.
Experiments were performed in unanaesthetized guinea-pigs in order to obtain direct evidence that the noradrenergic projections from locus coeruleus (L.C.) to cerebral cortex inhibit the acetylcholine (ACh) release. The animals were provided with left and right epidural cups, to collect outflowing ACh and with a stimulating electrode, positioned in the left L.C. The electrical stimulation of L.C. caused a significant reduction of ACh outflow from both parietal areas. This effect was abolished, reduced or prevented by phentolamine, phenoxybenzamine or reserpine plus alpha-mt pretreatment, hence showing to be alpha-mediated.


Ultraviolet-induced lenticular fluorescence: intraocular straylight affecting visual function.
Ultraviolet radiation (UVR) excitation of fluorophores within the crystalline lens results in intraocular straylight. These fluorescent emissions are known to increase with age. The visual effect of this increase in fluorescent straylight has not previously been published. In this study, the visual deficit associated with UV-induced lenticular fluorescence was measured for 61 normal subjects between the ages of 21 and 80 yr of age using the Regan visual acuity charts at varying levels of contrast. UVR was shown to decrease low contrast acuity and this loss increased linearly with age.


Implementing the international evidence-based guideline of assessment and management of polycystic ovary syndrome (PCOS): how to achieve weight loss in overweight and obese women with PCOS?
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. Many of these women are overweight or obese. A minor weight loss of 5%-10% can significantly reduce reproductive, metabolic and psychological symptoms of PCOS and is recommended as a first step in the treatment of overweight or obese women with PCOS. Many weight loss programs have been proposed, but optimal methods on how to achieve the recommend weight loss are lacking. The aim of this systematic review was to generate practical tools for health professionals to guide women with PCOS towards a sustainable healthier lifestyle. PRISMA guidelines were used to conduct the systematic review. Eleven randomized controlled trials were found eligible for inclusion. Lifestyle modification strategies consisted of a diet, physical exercise, behavioural coaching or combined interventions. Mean weight loss ranged from +0.5 to -10.6 % of the initial body weight. However, the majority of the studies reported considerable drop-out rates varying between 12% and 47%. The heterogeneity of the described interventions and the high drop-out rates impede extrapolation of these results to daily clinical care. Hence, none of the described interventions seems superior to another in achieving substantial weight loss. In conclusion, the need for obtaining a healthier weight in overweight and obese women with PCOS is now well accepted. However, achieving this goal remains a challenge for both patients and healthcare providers. More research focusing on the multidisciplinary approach of lifestyle modification advice in daily practice is needed.


Retracted: Comparative Analysis of Efficacy and Prognosis of Hemodialysis and Peritoneal Dialysis for End-Stage Renal Disease: A Meta-analysis.
[This retracts the article DOI: 10.1155/2022/6007698.].


Novel comparison of evaluation metrics for gene ontology classifiers reveals drastic performance differences.
Automated protein annotation using the Gene Ontology (GO) plays an important role in the biosciences. Evaluation has always been considered central to developing novel annotation methods, but little attention has been paid to the evaluation metrics themselves. Evaluation metrics define how well an annotation method performs and allows for them to be ranked against one another. Unfortunately, most of these metrics were adopted from the machine learning literature without establishing whether they were appropriate for GO annotations. We propose a novel approach for comparing GO evaluation metrics called Artificial Dilution Series (ADS). Our approach uses existing annotation data to generate a series of annotation sets with different levels of correctness (referred to as their signal level). We calculate the evaluation metric being tested for each annotation set in the series, allowing us to identify whether it can separate different signal levels. Finally, we contrast these results with several false positive annotation sets, which are designed to expose systematic weaknesses in GO assessment. We compared 37 evaluation metrics for GO annotation using ADS and identified drastic differences between metrics. We show that some metrics struggle to differentiate between different signal levels, while others give erroneously high scores to the false positive data sets. Based on our findings, we provide guidelines on which evaluation metrics perform well with the Gene Ontology and propose improvements to several well-known evaluation metrics. In general, we argue that evaluation metrics should be tested for their performance and we provide software for this purpose (https://bitbucket.org/plyusnin/ads/). ADS is applicable to other areas of science where the evaluation of prediction results is non-trivial.


Coronary Artery Bypass Grafting Transit Time Flow Measurement: Graft Patency and Clinical Outcomes.
This subanalysis of the Randomized On-Off Bypass (ROOBY) trial examined transit time flow measurement (TTFM) use and its impact on graft patency and long-term clinical outcomes after coronary artery bypass graft surgery. Use of TTFM for ROOBY centers and surgeons was assessed. Comparative patient outcomes based on TTFM use included 1-year graft patency and 1-year and 5-year major adverse cardiac events: all-cause mortality, nonfatal myocardial infarction, and revascularization (percutaneous coronary intervention or repeat coronary artery bypass graft surgery). Transit time flow measurement was used in 1067 patients (TTFM group) and not used in 501 patients (non-TTFM group); of the TTFM group, median percentage TTFM use was 79% (interquartile range, 41% to 98%) among 18 Veterans Affairs Medical Centers, and 74% (interquartile range, 13% to 98%) among 48 surgeons. Patients were comparable in age (63 ± 8.5 years TTFM vs 62 ± 8 years non-TTFM, P = .30) and estimated 30-day mortality risk (1.8 ± 1.7 TTFM vs 1.9 non-TTFM, P = .53). One-year FitzGibbon A patency was 83% (1600 of 1988 grafts) for TTFM assessed grafts and 78% (629 of 803) for non-TTFM assessed grafts (P < .01). Fewer TTFM patients had an occluded graft (29%, vs 38% non-TTFM; P = .01). Comparing TTFM patients with non-TTFM patients, 5-year major adverse cardiac event rates were 30% vs 25% (P = .06). Individual component rates were 14% vs 11% for death (P = .06), 12% vs 8.8% for myocardial infarction (P = .07), and 13% vs 12% for revascularization (P = .62). The association of TTFM use with graft patency and clinical outcome is uncertain. Future randomized studies that account for patient risk factors and practice variation would help address this knowledge gap.


Reported treatment of hypertension by family physicians in Sweden and Minnesota: a physician survey of practice habits.
To compare family physicians' reported practice habits on hypertension in Sweden and Minnesota, and to assess to what extent different national guidelines account for differences. Random samples of family physicians were selected for telephone interviews on their practice of hypertension. Primary care in southern Sweden and in Minnesota. Family medicine specialists. Participation rates were 236/264 (89%) in Sweden and 183/209 (88%) in Minnesota. Cut-off levels, and non-pharmacological and pharmacological treatment of hypertension, related to three case scenarios: a 48-year-old man, a 65-year-old man and a 65-year-old woman. Swedish physicians reported significantly higher levels of diastolic blood pressure than Minnesota physicians for the institution of treatment of hypertension for all case scenarios. In both countries, physicians adhered to the cut-off levels of their national guidelines in the case of the 48-year-old man. Minnesota physicians did not use age as a modifying factor for treatment cut-off levels, as did Swedish physicians. Swedish physicians emphasized alcohol, fat and stress reduction, and Minnesota physicians weight and salt reduction as non-pharmacological treatment. While Swedish physicians generally preferred beta-blockers, Minnesota physicians chose ACE inhibitors or calcium channel blockers as the first choice drug. Swedish and US guidelines on hypertension were identical except for higher cut-off level for drug treatment in Sweden. Minnesota physicians reported cut-off levels close to national guidelines. For 65-year-old patients, Swedish physicians reported applying a higher cut-off level than indicated by guidelines. Swedish physicians also reported preferring less expensive drugs. As a consequence of the differing national guidelines and the identified physicians' practice habits in the two medical communities, it is likely that the segments of the populations treated and the drug costs differ substantially.


Interferon-gamma is a target for binding and folding by both Escherichia coli chaperone model systems GroEL/GroES and DnaK/DnaJ/GrpE.
IFN-gamma can be physicochemically distinguished from interferons-alpha, -beta or -omega through the loss of its tertiary structure and biological activity upon exposure to acid or heat. This loss is due to the irreversible aggregation of an unfolded or partially folded state. The conformational instability of IFN-gamma is reflected by its impairment to fold properly when overexpressed in Escherichia coli, resulting in its accumulation in cytoplasmic inclusion bodies. Chaperones were originally identified as a heterogeneous group of proteins that mediate the folding and correct assembly of various polypeptide substrates, and protect thermolabile proteins against inactivation. In either of both cases, chaperones prevent irreversible misfolding by assisting the substrate protein along its pathway to a stable tertiary conformation. Among the best characterized chaperones are the Escherichia coli Hsp60 and Hsp70 heat shock protein complexes, i.e., GroEL/GroES and DnaK/DnaJ/GrpE. They exhibit entirely different reaction mechanisms, which, however, both depend on hydrolysis of ATP. The unfolding of recombinant IFN-gamma by acid or heat can be used as a tool to assess its in vitro interaction with each of both chaperone systems at physiological temperature (35 degrees C). Using such an experimental set-up, both the DnaK and GroEL chaperone systems appeared to form complexes with IFN-gamma from which correctly folded protein was released in an ATP-dependent manner. In addition to the biotechnological implication of these observations, the relevance to de novo folding of IFN-gamma is discussed.


Prevalence and predictive factors of dental anxiety in Brazilian adolescents.
The purpose of this study was to determine the prevalence and predicitve factors of dental anxiety among Brazilian adolescents. This was a cross-sectional study of a random sample of 340 Brazilian adolescents, done between 2005 and 2010. Corah's Dental Anxiety Scale and an objective questionnaire were used to determine the degree of dental anxiety. The prevalence of moderate to severe dental anxiety was approximately 18%. Dental anxiety was correlated with the following factors: gender (P<.05), age group (P<.001), degree of schooling (P<.001), access to newspapers and/or the Internet (P<02), oral hygiene frequency (P=.005), visits to the dentist (P<.02), reason for last visit to the dentist (P<.001), and experience with dental pain (P=.002). Dental fear and anxiety in Brazilian adolescents are associated with lack of economic resources, negligence of oral health, low educational level, female gender, and younger age.


Clinical, pathological, imaging, and genetic characterization in a Taiwanese cohort with limb-girdle muscular dystrophy.
Limb-girdle muscular dystrophy (LGMD) is a genetically heterogeneous, hereditary disease characterized by limb-girdle weakness and histologically dystrophic changes. The prevalence of each subtype of LGMD varies among different ethnic populations. This study for the first time analyzed the phenotypes and genotypes in Taiwanese patients with LGMD in a referral center for neuromuscular diseases (NMDs). We enrolled 102 patients clinically suspected of having LGMD who underwent muscle biopsy with subsequent genetic analysis in the previous 10 years. On the basis of different pathological categories, we performed sequencing of target genes or panel for NMDs and then identified patients with type 1B, 1E, 2A, 2B, 2D, 2I, 2G, 2 N, and 2Q. The 1B patients with LMNA mutation presented with mild limb-girdle weakness but no conduction defect at the time. All 1E patients with DES mutation exhibited predominantly proximal weakness along with distal weakness. In our cohort, 2B and 2I were the most frequent forms of LGMD; several common or founder mutations were identified, including c.1097_1099delACA (p.Asn366del) in DES, homozygous c.101G > T (p.Arg34Leu) in SGCA, homozygous c.26_33dup (p.Glu12Argfs*20) in TCAP, c.545A > G (p.Tyr182Cys), and c.948delC (p.Cys317Alafs*111) in FKRP. Clinically, the prevalence of dilated cardiomyopathy in our patients with LGMD2I aged > 18 years was 100%, much higher than that in European cohorts. The only patient with LGMD2Q with PLEC mutation did not exhibit skin lesions or gastrointestinal abnormalities but had mild facial weakness. Muscle imaging of LGMD1E and 2G revealed a more uniform involvement than did other LGMD types. Our study revealed that detailed clinical manifestation together with muscle pathology and imaging remain critical in guiding further molecular analyses and are crucial for establishing genotype-phenotype correlations. We also determined the common mutations and prevalence for different subtypes of LGMD in our cohort, which could be useful when providing specific care and personalized therapy to patients with LGMD.


Carcinogenesis in rats by cyclic N-nitrosamines containing sulphur.
The effects of chronic exposure to three sulphur-containing heterocyclic N-nitrosamines were determined after repeated oral administration to female Fischer 344 rats. Nitrosothiazolidine did not significantly affect the survival of the rats or the incidence of tumours at a total dose of 3.5 mmol. Nitrosodithiazine, an analogue of nitrosothiazolidine which contains an extra sulphur atom inserted between the carbons of its CH2-CH2 moiety, produced only three tumours (two of the nasal mucosa) in a group of 20 rats at a total dose of 1.75 mmol/rat. Nitrosothialdine, the all-cis 2,4,6-trimethyl analogue of nitrosodithiazine, was a potent carcinogen that significantly shortened the lifespan and produced oesophageal tumours in 70% of treated rats as well as numerous tumours of the tongue and liver; this outcome was unexpected because alpha-methyl substitution in other heterocyclic nitrosamines usually reduces or eliminates tumorigenicity. The results extend the data base on the carcinogenic activity of molecules containing both divalent sulphur and the nitrosamino function. The lack of significant carcinogenicity of nitrosothiazolidine in this study suggests that its presence in the human food supply presents a relatively minor risk.


Urethral diverticula in women.
Female urethral diverticula are rare, benign epithelium-lined outpouchings of the female urethra. Patients can present with a multitude of symptoms, most commonly urinary incontinence, recurrent UTIs and dyspareunia. These presenting symptoms are often confused with other diagnoses leading to delayed diagnosis or misdiagnosis. Diagnosis and preoperative assessment of bladder function is most accurate using a combination of clinical examination, T2-weighted postvoid MRI and videocystometrography. Best treatment is by vaginal excision, a procedure with a very low recurrence rate and high patient acceptability. Excision also results in high cure rates for associated dyspareunia, UTI and voiding dysfunction. Pre-existing urodynamically proven stress urinary incontinence (USUI) resolves in 50% of patients after excision of the diverticulum with Martius labial fat pad interposition without the need for further treatment. Potential adverse effects after surgery are new-onset USUI, urethrovaginal fistula and urethral stricture. The rate of onset of these potential adverse effects is low and related to the preoperative appearance of the diverticulum on an MRI scan and the complexity of the diverticulum.


Cerebrospinal fluid purinomics as a biomarker approach to predict outcome after severe traumatic brain injury.
Severe traumatic brain injury (TBI) is associated with high rates of mortality and long-term disability linked to neurochemical abnormalities. Although purine derivatives play important roles in TBI pathogenesis in preclinical models, little is known about potential changes in purine levels and their implications in human TBI. We assessed cerebrospinal fluid (CSF) levels of purines in severe TBI patients as potential biomarkers that predict mortality and long-term dysfunction. This was a cross-sectional study performed in 17 severe TBI patients (Glasgow Coma Scale <8) and 51 controls. Two to 4 h after admission to ICU, patients were submitted to ventricular drainage and CSF collection for quantification of adenine and guanine purine derivatives by HPLC. TBI patients' survival was followed up to 3 days from admission. A neurofunctional assessment was performed through the modified Rankin Scale (mRS) 2 years after ICU admission. Purine levels were compared between control and TBI patients, and between surviving and non-surviving patients. Relative to controls, TBI patients presented increased CSF levels of GDP, guanosine, adenosine, inosine, hypoxanthine, and xanthine. Further, GTP, GDP, IMP, and xanthine levels were different between surviving and non-surviving patients. Among the purines, guanosine was associated with improved mRS (p = 0.042; r = -0.506). Remarkably, GTP displayed predictive value (AUC = 0.841, p = 0.024) for discriminating survival versus non-survival patients up to 3 days from admission. These results support TBI-specific purine signatures, suggesting GTP as a promising biomarker of mortality and guanosine as an indicator of long-term functional disability.


Anaesthesia for facial rhytidectomy.
Observations on anaesthesia for facial rhytidectomy in 200 patients, without tracheal intubation or artificial ventilation, are reported in this survey.


Cultured marrow stromal cells express common acute lymphoblastic leukaemia antigen (CALLA): implications for marrow transplantation.
This study demonstrates the presence of an antigenic determinant associated with the common acute lymphoblastic leukaemia antigen (CALLA), and presumably CALLA itself, on stromal cells in normal human long-term marrow cultures by using two monoclonal anti-CALLA antibodies, J-5 and 24.1. Treatment of cultured stromal cells with antibody and complement resulted in the loss of most flat angulated cells and many of the fat-containing cells. However, long-term cultures were generated with cytotoxic antibody-treated marrow buffy coat cells, and the stromal cells in these cultures were also CALLA-positive. We conclude that CALLA-bearing stromal cells arise from CALLA-negative progenitors. CALLA therefore could be either a differentiation antigen acquired on mature marrow stromal cells or may arise as a proliferation-dependent antigen. These studies suggest that the generation of long-term cultures from cytotoxic antibody-treated marrow may be an appropriate in vitro model for the functional assessment of such marrow prior to its use in autologous transplantation.


Accuracy of dynamic navigation compared to static surgical guide for dental implant placement.
To compare the accuracy of dynamic navigation (DN) with a static surgical guide (SSG) for dental implant placement and the influence factors such as the experience of the surgeon and the implant sites. A total of 38 implants, which underwent the dynamic navigation, and 57 implants which underwent a static surgical guide were enrolled in the retrospective study. Coronal deviation, apical deviation, and angular deviation were compared between the DN and SSG groups, along with the different experience level of surgeons and implant sites in the DN group. There were no statistically significant differences between the DN and SSG groups, and the experience level of the surgeons and implant sites in the DN group. However, the apical deviation of the DN was slightly higher than the SSG group in the anterior teeth (P = 0.028), and the angular deviation of DN was smaller than the SSG group in the molar. Dynamic navigation can achieve accurate implant placement as well as the static surgical guide. Additionally, the experience level of the surgeon and implant site do not influence the accuracy of dynamic navigation, while the accuracy of DN seems higher than the SSG in molar.


Significance of IFN-ɤ/IL-2 Ratio as a Circulating Diagnostic Biomarker in Extrapulmonary Tuberculosis.
Extrapulmonary tuberculosis (EPTB) remains a challenging diagnosis both for clinicians and microbiologists. We hypothesized that the profile of IFN-ɤ/IL-2 ratio in clinically diagnosed cases of EPTB would be distinct from that of age- and sex-matched healthy controls. Therefore, in our study, we have assessed the ratio of serum levels of IFN-ɤ and IL-2 in clinically diagnosed cases of EPTB to assess their potential role as diagnostic biomarkers. Sixty-nine (69) clinically confirmed EPTB cases and 69 age- and sex-matched healthy controls were included in the study. All the extrapulmonary specimens were subjected to Ziehl-Neelsen staining for acid-fast bacilli and culture on Lowenstein-Jensen (LJ) medium. Detection of serum levels of IFN-ɤ and IL-2 was carried out using commercially available ELISA kits following manufacturers' instructions. The ratio of serum levels of IFN-ɤ and IFN-ɤ/IL-2 was discriminative for the diagnosis of EPTB cases (p < 0.001), although the same was not observed with IL-2 (p > 0.05). Distribution of all biomarkers significantly differed between culture-positive and culture-negative cases (p < 0.05). Among the smear-positive and smear-negative ones, only IFN-ɤ and IFN-ɤ/IL-2 ratio could significantly differentiate (p < 0.05). Ratio of IFN-ɤ and IL-2 rather than the individual levels was the best discriminatory biomarker with the highest area under the ROC curve. Although IFN-ɤ and IFN-ɤ/ IL-2 ratio could aid in the diagnosis of EPTB, IL-2 has a limited utility in the diagnosis of EPTB. Further elaborate studies to validate these results are required.


Minimally invasive percutaneous plate osteosynthesis (MIPPO) technique applied in the treatment of humeral shaft distal fractures through a lateral approach.
The minimally invasive percutaneous plate osteosynthesis (MIPPO) technique through the anterior approach has been successfully used in the treatment of humeral shaft fractures and has gained satisfactory clinical outcome. An anatomical study and a preliminary clinic report were performed to evaluate the feasibility of applying the MIPPO technique in the treatment of humeral shaft distal fractures through the lateral approach. This study was done on 14 arms from seven fresh cadavers. The results of this study showed that it is possible to treat humeral shaft distal fractures by using the MIPPO technique through the lateral approach. The results of using the MIPPO technique through the lateral approach in the treatment of humeral shaft fractures in 22 patients were also reviewed.


Beyond Kt/V: redefining adequacy of dialysis in the 21st century.
I presume that every dialysis patient needs a minimal amount of dialysis, since less dialysis will lead to death. Until we come up with a better index, for hemodialysis, I propose that we should return to Scribner's 1974 recommendation on adequacy of dialysis and concentrate on the homeostatic function of the kidney, as indicated in Table 1. For those who still want to measure dialysis dose by Kt/V, the optimal dose for HD is a Kt/V of 1.2/treatment and for PD 1.7/week. None of these would be adequate without good UF and control of patients' fluid status. Frequent (4, 5, 6 or 7 days/week) and prolonged dialyses (5-8 hours) should be the norm and I believe that the Hemodialysis Product should be used as a guide, pending confirmation by prospective studies. A high hemodialysis product reflects much more closely the function of the normal kidneys than 3-4 hours of dialysis three times a week with a Kt/V of 1.2 per session. Peritoneal dialysis that is already continuous needs to improve its efficiency. For PD patients, I believe that the total daily volume (Kt) might be a better index of adequacy, especially if it is combined with a good ultrafiltration (at least of 1 L/day) and blood pressure control. Of course, this has to be confirmed in the future. In the anuric patients, the daily volume can be kept to 8 L/day if the patient is free of symptoms, but should be increased to 10-12 L/day for CAPD and 15-20 L/day for APD patients if they develop symptoms of underdialysis and fluid overload.


Thiol-catalyzed formation of lactate and glycerate from glyceraldehyde.
The formation of lactate from glyceraldehyde is catalyzed by the thiol, N-acetylcysteine, at ambient temperature in aqueous sodium phosphate (pH 7.0). The rate of lactate formation is more rapid at higher concentrations of sodium phosphate and is essentially the same in the presence and absence of oxygen. The formation of lactate is efficient, but proceeds slowly with an 8.8% yield of lactate after 16 days from 10 mM glyceraldehyde in the presence of 12.5 mM N-acetylcysteine and 500 mM sodium phosphate (pH 7.0). The formation of glycerate from glyceraldehyde, that occurs in the presence of oxygen and to a small extent when oxygen has been removed, is also catalyzed by the thiol, N-acetylcysteine, under the same conditions. The dramatic increase in the rate of glycerate formation that is brought about by the thiol, N-acetylcysteine, is accompanied by an equally dramatic decrease in the rates of production of glycolate and formate. Presumably, the thiol-dependent formation of lactate and glycerate occurs via their respective thioesters. The significance of these reactions to molecular evolution is discussed.


Uxoricide by a schizophrenic patient with delusional misidentification syndromes: A case report.
Delusional misidentification syndromes in psychiatric disorders might result in dangerous behavior leading sometimes to homicide. An early diagnosis and thorough follow up is important to avoid such consequences.