Periodontal healing of replanted dog teeth stored in milk and egg albumen.
The type of storage medium used to store avulsed teeth prior to replantation has been shown to be a decisive factor in periodontal ligament (PDL) healing. The aim of the present study was to investigate the effect of storage medium on periodontal healing. Thirty teeth from three dogs were endodontically treated to prevent subsequent inflammatory root resorption. The teeth were atraumatically extracted and randomly stored in milk or egg albumen for 3, 6 and 10 h at 4 degrees C. All teeth were splinted for 1 weeks after replanting. After 2 months animals were sacrificed using vital perfusion-fixation and teeth were histologically prepared and evaluated following Andreasen's method. It was found that teeth stored in egg albumen for 6 and 10 h had significantly higher incident of PDL healing than those treated with milk for the same period (P < 0.05). . The highest incidence of PDL healing was observed in teeth stored in egg albumen for 6 h. The least surface resorption was also evident in this group (P < 0.05). The result of this study shows that egg albumen is an excellent storage media for up to 10 h considering its likely availability at most accident sites.


Split-Channel Ballistic Transport in an InSb Nanowire.
We report an experimental study of one-dimensional (1D) electronic transport in an InSb semiconducting nanowire. A total of three bottom gates are used to locally deplete the nanowire, creating a ballistic quantum point contact with only a few conducting channels. In a magnetic field, the Zeeman splitting of the corresponding 1D sub-bands is revealed by the emergence of conductance plateaus at multiples of e2/h, yet we find a quantized conductance pattern largely dependent on the configuration of voltages applied to the bottom gates. In particular, we can make the first plateau disappear, leaving a first conductance step of 2 e2/ h, which is indicative of a remarkable 2-fold sub-band degeneracy that can persist up to several tesla. For certain gate voltage settings, we also observe the presence of discrete resonant states producing conductance features that can resemble those expected from the opening of a helical gap in the sub-band structure. We explain our experimental findings through the formation of two spatially separated 1D conduction channels.


Dietary vitamin C and vitamin E interact to influence growth and tissue composition of juvenile hybrid striped bass (Morone chrysops (female) x M. saxatilis (male)) but have limited effects on immune responses.
Juvenile hybrid striped bass (initially 12.0 g) were fed diets containing deficient, adequate or excessive amounts of vitamin C and/or vitamin E in a factorial arrangement to investigate potential nutritional interaction and effects on immune responses. Nine semipurified diets were supplemented with 0, 25 or 2500 mg vitamin C/kg and 0, 30 or 300 mg vitamin E/kg and fed to fish in triplicate aquaria for 10 wk. Weight gain, feed efficiency, mortality and tissue vitamin levels were significantly (P < or = 0.05) affected by dietary vitamin levels. In addition, a significant interaction between vitamin C and vitamin E was observed. At inclusion levels of 25 and 2500 mg/kg, dietary vitamin C improved feed efficiency and protected fish fed vitamin E-deficient diets from growth depression and mortality. At inclusion levels of 30 and 300 mg/kg, vitamin E prevented mortality in fish fed vitamin C-deficient diets; however, 300 mg vitamin E/kg was necessary to prevent growth depression in vitamin C-deficient fish but was unable to improve feed efficiency. Lysozyme, bacterial killing ability, as well as plasma protein and total immunoglobulin levels of fish were not affected by dietary vitamin levels, whereas respiratory burst activity increased with vitamin E supplementation. Thus, interactions between vitamin C and vitamin E were observed in hybrid striped bass. These interactions may be due to the ability of vitamin C to regenerate vitamin E to its functional form but also suggest an ability of vitamin E to spare vitamin C.


Tremelimumab in Combination With Microwave Ablation in Patients With Refractory Biliary Tract Cancer.
Treatment options for patients with advanced biliary tract cancer are limited. Dysregulation of the immune system plays an important role in the pathogenesis of biliary tract cancer (BTC). This study aimed to investigate whether tremelimumab, an anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) inhibitor, could be combined safely with microwave ablation to enhance the effect of anti-CTLA4 treatment in patients with advanced BTC. Patients were enrolled to receive monthly tremelimumab (10 mg/kg, intravenously) for six doses, followed by infusions every 3 months until off-treatment criteria were met. Thirty-six days after the first tremelimumab dose, patients underwent subtotal microwave ablation. Interval imaging studies were performed every 8 weeks. Adverse events (AEs) were noted and managed. Tumor and peripheral blood samples were collected to perform immune monitoring and whole-exome sequencing (WES). Twenty patients with refractory BTC were enrolled (median age, 56.5 years). No dose-limiting toxicities were encountered. The common treatment-related AEs included lymphopenia, diarrhea, and elevated transaminases. Among 16 patients evaluable for efficacy analysis, 2 (12.5%) patients achieved a confirmed partial response (lasting for 8.0 and 18.1 months, respectively) and 5 patients (31.3%) achieved stable disease. Median progression free survival (PFS) and overall survival (OS) were 3.4 months (95% confidence interval [CI], 2.5-5.2) and 6.0 months (95% CI, 3.8-8.8), respectively. Peripheral blood immune cell subset profiling showed increased circulating activated human leukocyte antigen, DR isotype ([HLA-DR] positive) CD8+ T cells. T-cell receptor (TCR)β screening showed tremelimumab expanded TCR repertoire, but not reaching statistical significance (P = 0.057). Conclusion: Tremelimumab in combination with tumor ablation is a potential treatment strategy for patients with advanced BTC. Increased circulating activated CD8+ T cells and TCR repertoire expansion induced by tremelimumab may contribute to treatment benefit.


Three-dimensional structure of the L-threonine-O-3-phosphate decarboxylase (CobD) enzyme from Salmonella enterica.
The three-dimensional structure of the pyridoxal 5'-phosphate (PLP)-dependent L-threonine-O-3-phosphate decarboxylase (CobD) from Salmonella enterica is described here. This enzyme is responsible for synthesizing (R)-1-amino-2-propanol phosphate which is the precursor for the linkage between the nucleotide loop and the corrin ring in cobalamin. The molecule is a molecular dimer where each subunit consists of a large and small domain. Overall the protein is very similar to the members of the family of aspartate aminotransferases. Indeed, the arrangement of the ligands surrounding the cofactor and putative substrate binding site are remarkably close to that observed in histidinol phosphate aminotransferase, which suggests that this latter enzyme might have been its progenitor. The only significant differences in structure occur at the N-terminus, which is approximately 12 residues shorter in CobD and does not form the same type of interdomain interaction common to other aminotransferases. CobD is unusual since within the aspartate aminotransferase subfamily of PLP-dependent enzymes the chemical transformations are substantially conserved, where the only exceptions are 1-aminocyclopropane-1-carboxylate synthase and CobD. Although there are a large number of PLP-dependent amino acid decarboxylases, these are generally larger and structurally distinct from the members of the aspartate aminotransferase subfamily of enzymes. The structure of CobD suggests that the chemical fate of the external aldimine can be redirected by modifications at the N-terminus of the protein. This study provides insight into the evolutionary history of the cobalamin biosynthetic pathway and raises the question of why most PLP-dependent decarboxylases are considerably larger enzymes.


Inactivation of ompR promotes precocious swarming and flhDC expression in Xenorhabdus nematophila.
The response regulator OmpR is involved in numerous adaptive responses to environmental challenges. The role that OmpR plays in swarming behavior and swarm-cell differentiation in the symbiotic-pathogenic bacterium Xenorhabdus nematophila was examined in this study. Swarming began 4 h sooner in an ompR mutant strain than in wild-type cells. Precocious swarming was correlated with elevated expression of fliC, early flagellation, and cell elongation. The level of flhDC mRNA was elevated during the early period of swarming in the ompR strain relative to the level in the wild type. These findings show that OmpR is involved in the temporal regulation of flhDC expression and flagellum production and demonstrate that this response regulator plays a role in the swarming behavior of X. nematophila.


PODO/TERT256 - A promising human immortalized podocyte cell line and its potential use for in vitro research at different oxygen levels.
Podocytes are of key interest for the prediction of nephrotoxicity as they are especially sensitive to toxic insults due to their central role in the glomerular filtration apparatus. However, currently, prediction of nephrotoxicity in humans remains insufficiently reliable, thus highlighting the need for advanced in vitro model systems using human cells with improved prediction capacity. Recent approaches for refining in vitro model systems focus on closely replicating physiological conditions as observed under the in vivo situation typical of the respective nephron section of interest. PODO/TERT256, a human immortalized podocyte cell line, were employed in a semi-static transwell system to evaluate its potential use as a human podocyte in vitro system for modelling potential human glomerular toxicity. Furthermore, the impact of routinely employed excessive oxygen tension (21 % - AtmOx), when compared to the physiological oxygen tensions (10 % - PhysOx) observed in vivo, was analyzed. Generally, cultured PODO/TERT256 formed a stable, contact-inhibited monolayer with typical podocyte morphology (large cell body, apical microvilli, finger-like cytoplasmic projections (reminiscent of foot processes), and interdigitating cell-cell junctions) and developed a size-selective filtration barrier. PhysOx, however, induced a more pronounced in vivo like phenotype, comprised of significantly larger cell bodies, significantly enhanced filtration barrier size-selectivity, and a remarkable re-localization of nephrin to the cell membrane, thus suggesting an improved in vitro replication of in vivo characteristics. Preliminary toxicity characterization with the known glomerulotoxin doxorubicin (DOX) suggested an increasing change in filtration permeability, already at the lowest DOX concentrations tested (0.01 μM) under PhysOx, whereas obvious changes under AtmOx were observed as of 0.16 μM and higher with a near all or nothing effect. The latter findings suggested that PODO/TERT256 could serve as an in vitro human podocyte model for studying glomerulotoxicity, whereby culturing at PhyOx tension appeared critical for an improved in vivo-like phenotype and functionality. Moreover, PODO/TERT256 could be incorporated into advanced human glomerulus systems in vitro, recapitulating microfluidic conditions and multiple cell types (endothelial and mesenchymal cells) that can even better predict human glomerular toxicity.


Protective effects of gonadal hormones on spinal motoneurons following spinal cord injury.
Spinal cord injury (SCI) results in lesions that destroy tissue and disrupt spinal tracts, producing deficits in locomotor and autonomic function. The majority of treatment strategies after SCI have concentrated on the damaged spinal cord, for example working to reduce lesion size or spread, or encouraging regrowth of severed descending axonal projections through the lesion, hoping to re-establish synaptic connectivity with caudal targets. In our work, we have focused on a novel target for treatment after SCI, surviving spinal motoneurons and their target musculature, with the hope of developing effective treatments to preserve or restore lost function following SCI. We previously demonstrated that motoneurons, and the muscles they innervate, show pronounced atrophy after SCI. Importantly, SCI-induced atrophy of motoneuron dendrites can be attenuated by treatment with gonadal hormones, testosterone and its active metabolites, estradiol and dihydrotestosterone. Similarly, SCI-induced reductions in muscle fiber cross-sectional areas can be prevented by treatment with androgens. Together, these findings suggest that regressive changes in motoneuron and muscle morphology seen after SCI can be ameliorated by treatment with gonadal hormones, further supporting a role for steroid hormones as neurotherapeutic agents in the injured nervous system.


Does Wrist Arthrodesis With Structural Iliac Crest Bone Graft After Wide Resection of Distal Radius Giant Cell Tumor Result in Satisfactory Function and Local Control?
Many techniques have been described for reconstruction after distal radius resection for giant cell tumor with none being clearly superior. The favored technique at our institution is total wrist fusion with autogenous nonvascularized structural iliac crest bone graft because it is structurally robust, avoids the complications associated with obtaining autologous fibula graft, and is useful in areas where bone banks are not available. However, the success of arthrodesis and the functional outcomes with this approach, to our knowledge, have only been limitedly reported. (1) What is the success of union of these grafts and how long does it take? (2) How effective is the technique in achieving tumor control? (3) What complications occur with this type of arthrodesis? (4) What are the functional results of wrist arthrodesis by this technique for treating giant cell tumor of the distal radius? Between 2005 and 2013, 48 patients were treated for biopsy-confirmed Campanacci Grade III giant cell tumor of the distal radius. Of those, 39 (81% [39 of 48]) were treated with wrist arthrodesis using autogenous nonvascularized iliac crest bone graft. Of those, 27 (69% [27 of 39]) were available for followup at a minimum of 24 months (mean, 45 months; range, 24-103 months). During that period, the general indications for this approach were Campanacci Grade III and estimated resection length of 8 cm or less. Followup included clinical and radiographic assessment and functional assessment using the Disabilities of the Arm, Shoulder and Hand (DASH) score, the Musculoskeletal Tumor Society (MSTS) score, grip strength, and range of motion at every followup by the treating surgeon and his team. All functional results were from the latest followup of each patient. Union of the distal junction occurred at a mean of 4 months (± 2 months) and union of the proximal junction occurred at a mean of 9 months (± 5 months). Accounting for competing events, at 12 months, the rate of proximal junction union was 56% (95% confidence interval [CI], 35%-72%), whereas it was 67% (95% CI, 45%-82%) at 18 months. In total, 11 of the 27 patients (41%) underwent repeat surgery on the distal radius, including eight patients (30%) who had complications and three (11%) who had local recurrence. The mean DASH score was 9 (± 7) (value range, 0-100, with lower scores representing better function), and the mean MSTS 1987 score was 29 (± 1) (value range, 0-30, with higher scores representing better function) as well as 96% (± 4%) of mean MSTS 1993 score (value range, 0%-100%, with higher scores representing better function). The mean grip strength was 51% (± 23%) of the uninvolved side, whereas the mean arc of forearm rotation was 113° (± 49°). Reconstruction of defects after resection of giant cell tumor of the distal radius with autogenous structural iliac crest bone graft is a facile technique that can be used to achieve favorable functional results with complications and recurrences comparable to those of other reported techniques. We cannot show that this technique is superior to other options, but it seems to be a reasonable option to consider when other reconstruction options such as allografts are not available. Level IV, therapeutic study.


Bioactivity of nitrolinoleate: effects on adhesion molecules and CD40-CD40L system.
The vascular effects of nitrolinoleate (LNO2), an endogenous product of linoleic acid (LA) nitration by nitric oxide-derived species and a potential nitrosating agent, were investigated on rat endothelial-leukocyte interactions. Confocal microscopy analysis demonstrated that LNO2 was capable to deliver free radical nitric oxide (*NO) into cells, 5 min after its administration to cultured cells, with a peak of liberation at 30 min. THP-1 monocytes incubated with LNO2 for 5 min presented nitrosation of CD40, leading to its inactivation. Other anti-inflammatory actions of LNO2 were observed in vivo by intravital microscopy assays. LNO2 decreased the number of adhered leukocytes in postcapillary venules of the mesentery network. In addition to this, LNO2 reduced mRNA and protein expression of beta2-integrin in circulating leukocytes, as well as VCAM-1 in endothelial cells isolated from postcapillary venules, confirming its antiadhesive effects on both cell types. Moreover, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a nitric oxide scavenger, partially abolished the inhibitory action of LNO2 on leukocyte-endothelium interaction, suggesting that the antiadhesion effects of LNO2 involve a dual role in leukocyte adhesion, acting as a nitric oxide donor as well as through nitric oxide-independent mechanisms. In conclusion, LNO2 inhibited adhesion molecules expression and promoted *NO inactivation of the CD40-CD40L system, both important processes of the inflammatory response.


[Physician-patient rapport in practice and clinical research: what do medical students think?].
To investigate attitudes of medical students from the first, fourth and sixth year towards information of patients in clinical research and practice settings. A multiple-choice questionnaire was administered. Responses were registered on anonymous response-forms. The study was conducted at the two Schools of Medicine of Naples, in southern Italy. 773 students answered the questionnaire. Students believe that the quality of patient care is better within than outside a clinical trial, but anxiety and fear are the most frequent reactions to the idea of being offered the opportunity of participating, as patients, in a clinical trial. The patients' right to be informed of their participation in a clinical experiment is omitted by 30 to 50% of students. The majority of students believe that doctor's uncertainty should not be disclosed. About one-third believe that possible benefits of treatment should not be presented to patients and about one-fifth believe that information on possible drawbacks of treatment should be omitted. Many students believe that information on alternative types of treatment should be denied to patients entering a trial. Fourth year students consistently reported the highest percentage of negative responses. In clinical practice, as compared with clinical research, there is a higher tendency of students to give information to patients. The doctor's role is predominant when students indicate who should decide how much information to give to a patient entering into a clinical trial. Medical education should focus more closely on uncertainty and error analysis; principles of medical research and ethics should be covered throughout academic medical training.


[Mutagenic effect of the herbicide Titus in maize].
Mutagenic effect of the new herbicide titus has been studied by the tests of chromosome aberration and gene mutations in maize. It has been shown that the preparation in question possesses a definite mutagenic activity, which sometimes 5-7 times exceeded the level of spontaneous mutating. Therefore, when recommending it for application in agriculture it is necessary strict following recommended doses, because even slight excess may result in considerable genetic consequences. It is also of great importance to apply this herbicide during the recommended stage. The application of titus for maize in hybridization plots as well as in nurseries for reproduction of elite and super elite lines is not recommended.


Activation of N-methyl-D-aspartate receptors by glycine: role of an aspartate residue in the M3-M4 loop of the NR1 subunit.
Glutamate and glycine are coagonists that act at distinct sites to activate N-methyl-D-aspartate (NMDA) receptors. In the NR1 subunit of the NMDA receptor, mutation of D732 to glutamate (D732E), asparagine (D732N), alanine (D732A), or glycine (D732G) reduced the potency of glycine by > 4000-fold, but these mutations had no effect on sensitivity to glutamate. Mutations at NR1(D732) also changed sensitivity to the glycine-site agonists D-serine and D-alanine, reducing the potencies and, in some cases, the efficacies of these compounds. Thus, D-serine was a full agonist at the glycine site of receptors containing NR1(D732N) and NR1(D732A), a partial agonist at receptors containing NR1(D732G), and a competitive antagonist at receptors containing NR1(D732). Mutations at NR1(D732) had no effect or produced an increase in sensitivity to the glycine-site antagonists 6,7-dichloroquinoxaline-2,3-dione and 5,7-dichlorokynurenic acid. These mutations did not affect the reversal potential, voltage-dependent block by extracellular Mg2+, block by ifenprodil, or stimulation by spermine at NR1/NR2B receptors. NR2 subunits containing mutations at NR2A(D731) and NR2B(D732), which correspond to NR1(D732), did not produce functional receptors when coexpressed with NR1. Residue D732 in NR1 may be close to a glycine binding site on the NMDA receptor and may directly affect the properties of this site or be critical for coupling of glycine binding to channel activation.


Synthetic surfactant for respiratory distress syndrome in preterm infants.
This section is under preparation and will be included in the next issue. To assess the effect of intratracheal administration of synthetic surfactant in premature newborns with established respiratory distress syndrome (RDS). Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactants; limits: age groups, newborn infant; publication types, clinical trial), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language. Randomized controlled trials which compared the effect of synthetic surfactant treatment to routine management in the treatment of preterm infants with respiratory distress syndrome. Data regarding clinical outcome including the incidence of pneumothorax, pulmonary interstitial emphysema, pulmonary hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, apnea of prematurity, intraventricular hemorrhage (any grade, and severe intraventricular hemorrhage), bronchopulmonary dysplasia, neonatal mortality, bronchopulmonary dysplasia or death, retinopathy of prematurity (any retinopathy, and retinopathy greater than Stage 3), mortality at hospital discharge, mortality to one year of age, and cerebral palsy (any, and moderate/severe cerebral palsy) was excerpted from the report of the clinical trials by the reviewer. Data were analyzed according to the standards of the Cochrane Neonatal Review Group. Six randomized controlled trials of synthetic surfactant treatment of established respiratory distress syndrome were identified. Five of the studies used Exosurf Neonatal (a synthetic surfactant composed of dipalmitoylphosphatidylcholine, hexadecanol and tyloxapol); one small study utilized a mixture of dipalmitoylphosphatidylcholine (DPPC) and phosphatidylglycerol (PG). Treatment with intratracheal Exosurf Neonatal in premature infants with established respiratory distress syndrome improves pulmonary gas exchange and decreases the requirement for ventilatory support. In individual trials, the use of Exosurf Neonatal resulted in a statistically significant reduction in pneumothorax, patent ductus arteriosus, bronchopulmonary dysplasia (BPD), BPD or death at 28 days, and mortality. Similar results are seen when these large trials of Exosurf Neonatal are analyzed in conjunction with the smaller trial of dry powdered DPPC and phosphatidylglycerol (PG). The meta-analysis supports a decrease in the risk of pneumothorax (typical relative risk 0.64, 95% CI 0.55, 0.76, typical risk difference -0.09, 95% CI -0.12,-0.06), a decrease in the risk of pulmonary interstitial emphysema (typical relative risk 0.62, 95% CI 0.54, 0.71, typical risk difference -0.12, 95% CI -0.16, -0.09), a decrease in the risk of patent ductus arteriosus (typical relative risk 0.90, 95% CI 0.84, 0.97; typical risk difference -0.06 95% CI -0.10, -0.02), a decrease in the risk of intraventricular hemorrhage (typical relative risk 0.88, 95% CI 0.77, 0.99; typical risk difference -0.04, 95% CI -0.08, -0.00), a decrease in the risk of bronchopulmonary dysplasia (typical relative risk 0.75, 95% CI 0.61, 0.92; typical risk difference -0.04, 95% CI -0.06, -0.01), a decrease in the risk of neonatal mortality (typical relative risk 0. 73, 95% CI 0.61, 0.88; typical risk difference -0.05, 95% CI -0.07, -0.02), a decrease in the risk of bronchopulmonary dysplasia or death at 28 days (typical relative risk 0.73, 95% CI 0.65, 0.83; typical risk difference -0.06, 95% CI -0.11, -0.05), a decrease in the risk of mortality prior to hospital discharge (typical relative risk 0.79, 95% CI 0.68, 0.92; typical risk difference -0.05, 95% CI -0.07, -0.02) and a decrease in the risk of mortality during the first year of life (typical relative risk 0.80, 95% CI 0.69, 0.94; typical risk difference -0.04, 95% CI -0.07, -0.01). (ABS


A literature survey of the potentially adverse effects of the drugs commonly prescribed for the elderly.
Part I: Hard data concerning adverse drug reactions are notoriously difficult to obtain. Some of the problems arise because of: --patient variables including age, sex, genetic differences, and current illness. --multiple drug use, continuation of smoking, and use of alcohol. --variations in dose, duration of treatment, and route of administration. --some effects are not reported but many reported effects are not truly due to the drug indicated. Nevertheless, we need to be aware of potential adverse reactions. Our ability to recognize drug side effects will be improved if we have some idea which kinds of reaction may occur. Part I deals with the analgesics, sedatives, laxatives, antacids, antidiabetic agents, antihypertensives and cardiovascular drugs. Potential systemic and ocular adverse reactions are listed.


A 59-year-old woman gives birth to twins--when should a fertility specialist refuse treatment?
To review cases of infertility where despite extremely low odds of success and potential risks to the woman if she became pregnant or to the fetus, the couples elected to take a chance to fulfill their dreams of having a baby. Six cases are described: case 1, a 59-year-old woman with hyperstimulation and intramuscular fibroids compressing the uterine cavity who wanted to be a donor egg recipient; case 2, a 59-year-old woman desiring a second transfer of sibling frozen embryos who had previously conceived with donor eggs at age 57; case 3, a 33-year-old woman with a subseptated uterus and cervical abnormality from intrauterine diethilstibesterol exposure plus hemoaphilia trait, and only 25% of her liver remaining from a previous partial liver resection; case 4, a woman with an unicornuate uterus refusing reduction of her twins to a singleton; case 5, a 39-year-old woman willing to try again to have her first live born child with a history of a large macroprolactinoma that was resected but markedly enlarged in her previous pregnancy despite bromocryptine therapy; and, case 6, a woman willing to try a unique experimental therapy with extremely high thyroid stimulating immunoglobulins to inhibit severe intrauterine growth retardation and potential premature synostosis for her condition of Hashimoto's disease. Cases 2-5 all had successful outcomes. Case 1 was never given the chance for donor oocytes since she was rejected by a majority vote of our physicians because of the fear of a malpractice suit. If a couple understands the potential risks and the low odds of success, they should be given the opportunity to fulfill their dreams of having a baby. However, treating physicians are under no obligation to take malpractice risks.


Tailored microarray platform for the detection of marine toxins.
Currently, there are no fast in vitro broad spectrum screening bioassays for the detection of marine toxins. The aim of this study was to develop such an assay. In gene expression profiling experiments 17 marker genes were provisionally selected that were differentially regulated in human intestinal Caco-2 cells upon exposure to the lipophilic shellfish poisons azaspiracid-1 (AZA1) or dinophysis toxin-1 (DTX1). These 17 genes together with two control genes were the basis for the design of a tailored microarray platform for the detection of these marine toxins and potentially others. Five out of the 17 selected marker genes on this dedicated DNA microarray gave clear signals, whereby the resulting fingerprints could be used to detect these toxins. CEACAM1, DDIT4, and TUBB3 were up-regulated by both AZA1 and DTX1, TRIB3 was up-regulated by AZA1 only, and OSR2 by DTX1 only. Analysis by singleplex qRT-PCR revealed the up- and down-regulation of the selected RGS16 and NPPB marker genes by DTX1, that were not envisioned by the new developed dedicated array. The qRT-PCR targeting the DDIT4, RSG16 and NPPB genes thus already resulted in a specific pattern for AZA1 and DTX1 indicating that for this specific case qRT-PCR might a be more suitable approach than a dedicated array.


[Ischemic brain infarction after an air embolism. Case report].
Ischemic stroke due to embolic air is uncommon. There are few reports of patients with air embolic stroke as a complication of endoscopic procedures. The temporal relationship between the stroke and this procedure is the most important clue for the diagnosis. CT scan and MRI of the brain are confirmatory tests. The morbidity and mortality is high. Patients should be hospitalized in a critical care service and treated as soon as possible with oxygen in a pressure camera. We report a 52 years old woman with an ovarian cancer that, during an upper gastrointestinal endoscopy, had a severe alteration of consciousness that did not respond to the use of Flumazenil. A CT scan showed multiple areas of air embolism in the watershed area between anterior and middle right cerebral arteries. A conservative treatment was decided and the patients died 48 hours later.


Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein.
The three-dimensional structure of acetylcholinesterase from Torpedo californica electric organ has been determined by x-ray analysis to 2.8 angstrom resolution. The form crystallized is the glycolipid-anchored homodimer that was purified subsequent to solubilization with a bacterial phosphatidylinositol-specific phospholipase C. The enzyme monomer is an alpha/beta protein that contains 537 amino acids. It consists of a 12-stranded mixed beta sheet surrounded by 14 alpha helices and bears a striking resemblance to several hydrolase structures including dienelactone hydrolase, serine carboxypeptidase-II, three neutral lipases, and haloalkane dehalogenase. The active site is unusual because it contains Glu, not Asp, in the Ser-His-acid catalytic triad and because the relation of the triad to the rest of the protein approximates a mirror image of that seen in the serine proteases. Furthermore, the active site lies near the bottom of a deep and narrow gorge that reaches halfway into the protein. Modeling of acetylcholine binding to the enzyme suggests that the quaternary ammonium ion is bound not to a negatively charged "anionic" site, but rather to some of the 14 aromatic residues that line the gorge.


Nitric oxide metabolites and interleukin-6 in cerebrospinal fluid from multiple sclerosis patients.
Interleukin-6 (IL-6) and nitric oxide (NO) are implicated in the pathology of multiple sclerosis (MS). We have investigated the levels of these mediators in the cerebrospinal fluid (CSF) from 50 patients with MS and 23 control subjects. Mean CSF IL-6 level was higher in the total MS group in comparison with controls, but not significantly, whilst the difference between patients with stable MS and controls reached the level of statistical significance. Mean CSF nitrite/nitrate level was significantly higher in the total MS group compared with the control group, as well as in active MS patients versus controls. There was significant difference neither in the mean CSF IL-6 nor in nitrite/nitrate levels between active and stable MS patients. Interestingly, we observed a significant negative correlation between IL-6 and nitrite/nitrate levels in the CSF in the total MS group. Such a trend existed in both subgroups with active and stable MS, but without reaching the level of statistical significance. Our data further support the involvement of IL-6 and NO in ongoing pathological processes in MS, suggesting their potential interplay within the central nervous system in this disease.


Genetic polymorphism and toxicology--with emphasis on cytochrome p450.
Individual susceptibility to environmental, chemical, and drug toxicity is to some extent determined by polymorphism in drug-metabolizing enzymes, in particular the cytochromes P450 (CYPs). This polymorphism is in particular translated into risk differences concerning drugs metabolized by the highly polymorphic enzymes CYP2C9, CYP2C19, and CYP2D6, whereas CYP enzymes active in procarcinogen activation are relatively well conserved without important functional polymorphisms. Examples of drug toxicities that can be predicted by P450 polymorphism include those exerted by codeine, tramadol, warfarin, acenocoumarol, and clopidogrel. The polymorphic CYP2A6 has a role in nicotine metabolism and smoking behavior. Besides this genetic variation, genome-wide association studies now allow for the identification of an increasing number of predictive genetic biomarkers among, e.g., human leukocyte antigens and to some extent drug transporters that provide useful information regarding the choice of the drug and drug dosage in order to avoid toxicity. The translation of this information into the clinical practice has been slow; however, an increasing number of pharmacogenomic drug labels are assigned, where the predictive genotyping before drug treatment can be mandatory, recommended, or only for informational purposes. In this review, we provide an update of the field with emphasis on CYP polymorphism.


Cigarette smoking and alcohol consumption associated with gastro-oesophageal reflux disease in Japanese men.
Associations between lifestyle factors and gastro-oesophageal reflux disease (GORD) have been conflicting. We aimed to examine these associations in Japanese men. We performed a cross-sectional study of Japanese male workers who visit a clinic for a routine health check-up and asked them to fill out a self-report questionnaire. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for GORD, defined as heartburn and/or acid regurgitation at least twice weekly. Of the 4095 eligible subjects, 276 (6.7%) were diagnosed as having GORD. Current smoking was significantly associated with CORD compared with non-smoking (OR = 1.35, 95% CI, 1.01-1.82). Moderate drinking (16-37 mL/day) and heavy drinking (> or = 38 mL/day) were also associated with GORD, while age and body mass index were not. After adjustment for age, daily alcohol consumption and body mass index, an increase in number of pack-years of cigarette smoking was significantly associated with an increased OR of GORD (P for trend = 0.034), and the OR for persons whose number of pack-years of cigarette smoking was more than 20.1 was 1.45 (CI 1.04-2.04) compared with non-smokers. Cigarette smoking and alcohol consumption are associated with an increased odds ratio for GORD in Japanese men.


Comparison of subjective and objective assessments of outcome after traumatic brain injury using the International Classification of Functioning, Disability and Health (ICF).
The aim is to examine two aspects of outcome after traumatic brain injury (TBI). Functional outcome was assessed by the Glasgow Outcome Scale - Extended (GOSE) and by clinician ratings, while health-related quality of life (HRQoL) was assessed by the Quality of Life after Brain Injury (QOLIBRI). The GOSE and the QOLIBRI were linked to the International Classification of Functioning, Disability and Health (ICF) to analyse their content. Functional outcome on ICF categories was assessed by rehabilitation clinicians in 55 participants with TBI and was compared to the participants' own judgements of their HRQoL. The QOLIBRI was linked to 42 and the GOSE to 57 two-level ICF categories covering 78% of the categories on the ICF brief core set for TBI. The closest agreement in the views of the professionals and the participants was found on the Physical Problems and Cognition scales of the QOLIBRI. The problems encountered after TBI are well covered by the QOLIBRI and the GOSE. They capture important domains that are not traditionally sufficiently documented, especially in the domains of interpersonal relationships, social and leisure activities, self and the environment. The findings indicate that they are useful and complementary outcome measures for TBI. In rehabilitation, they can serve as tools in assessment, setting meaningful goals and creating therapeutic alliance.


Short-Term Outcome of Ischemic Stroke Patients With Systemic Malignancy.
Background and Purpose- Recent guidelines have suggested the potential benefit of intravenous thrombolysis in stroke patients with systemic malignancy who have a reasonable life expectancy of >6 months. However, it is difficult to determine which patients with cancer will have a life expectancy of >6 months. Therefore, we identified the factors associated with 6-month mortality in patients with acute ischemic stroke and systemic malignancy. Methods- Consecutive stroke patients with systemic malignancy were retrospectively analyzed. We classified the patients into 3 groups: the nonactive cancer, active nonmetastatic cancer, and metastatic cancer groups. We compared the baseline characteristics and 6-month survival rates. Results- Of the 468 ischemic stroke patients with systemic malignancy during an 8-year period, 223 patients had nonactive cancer, 105 patients had active nonmetastatic cancer, and 140 patients had metastasis. During the 6-month follow-up, 122 patients (26.1%) died (nonactive cancer group [7.2%, 16/223], active nonmetastatic cancer group [11.4%, 12/105], and metastatic cancer group [67.1%, 94/140]). Multivariate Cox regression analysis revealed that the presence of metastasis (hazard ratio, 4.527; 95% CI, 2.175-9.422) was independently associated with 6-month mortality. However, the active nonmetastatic cancer group exhibited similar 6-month mortality to the nonactive cancer group (hazard ratio, 0.711; 95% CI, 0.282-1.795). Gastric/esophageal cancer and pancreatic cancer were also independently associated with 6-month mortality (hazard ratio, 2.068 and 2.389, respectively). Conclusions- In stroke patients with active cancer, the presence of metastasis and the cancer type were crucial factors associated with 6-month mortality.


Prognostic value of proliferating cell nuclear antigen in gastric carcinoma.
A new monoclonal antibody to proliferating cell nuclear antigen (PCNA), PC10, which can be used on routinely processed tissue, was applied to 93 cases of gastric carcinoma. Significant intra-tumoural variation in staining occurred. In addition to a PCNA index (percentage of positive cells per 1000 tumour cells), a semiquantitative PCNA grading system was devised, based on estimates of less than or more than 50% of positive tumour cells in whole sections. Neither PCNA index nor PCNA grade showed any correlation with established histological variables, tumour stage, or the presence of lymph node metastases. No significant correlation was observed between PCNA index and S + G2M phase fraction measured by flow cytometric analysis. To analyse survival tumours with PCNA indices above and below the median level (41%) were compared. Those with a higher index tended to have a worse prognosis, but when PCNA grade was considered, it was found to have definite independent prognostic value, tumours of low grade surviving better than those of high grade. The ability of semiquantitative PCNA grading to allow for intra-tumoural variation suggests it may have advantages over absolute counting, which is prone to sampling error when tumour heterogeneity is a major factor. The prognostic value of PC10 staining in gastric carcinoma is therefore promising.


Quantification of Heavy Metals in Mining Affected Soil and Their Bioaccumulation in Native Plant Species.
Several anthropogenic and natural sources are considered as the primary sources of toxic metals in the environment. The current study investigates the level of heavy metals contamination in the flora associated with serpentine soil along the Mafic and Ultramafic rocks northern-Pakistan. Soil and wild native plant species were collected from chromites mining affected areas and analyzed for heavy metals (Cr, Ni, Fe, Mn, Co, Cu and Zn) using atomic absorption spectrometer (AAS-PEA-700). The heavy metal concentrations were significantly (p < 0.01) higher in mine affected soil as compared to reference soil, however Cr and Ni exceeded maximum allowable limit (250 and 60 mg kg(-1), respectively) set by SEPA for soil. Inter-metal correlations between soil, roots and shoots showed that the sources of contamination of heavy metals were mainly associated with chromites mining. All the plant species accumulated significantly higher concentrations of heavy metals as compared to reference plant. The open dumping of mine wastes can create serious problems (food crops and drinking water contamination with heavy metals) for local community of the study area. The native wild plant species (Nepeta cataria, Impatiens bicolor royle, Tegetis minuta) growing on mining affected sites may be used for soil reclamation contaminated with heavy metals.


[Effectiveness of the inhalatory administration of chlolincocin in experimental staphylococcal pneumonia].
Administration of chlolincocin (7-chlor-7-desoxylincomycin) in the form of inhalation aerosol to albino mice in a dose of 200 Units/mouse provided the drug therapeutic concentrations in the lung tissue. The antibiotic was well adsorbed and detected in the blood, liver, kidneys and other biological substrates. Penetration of chlolincocin and lincomycin from the lungs into the blood was better in healthy animals. In animals with experimental staphylococcal infection their blood levels were 1.5--2 times lower. Repeated inhalations of chlolincocin resulted in an increase resulted in its levels in the lung tissue up to 8--10 Units/ml, however, its blood levels increased insignificantly. When chlolincocin and lincomycin were administered intravenously, their concentrations in the lung tissue were lower and detected for a shorter period of time than after the inhalation administration. The aerosols of chlolincocin markedly inhibited the growth of Staph. aureus in the lungs. The drug was 3--5 times more active than lincomycin. Inhalation administration of chlolincocin aerosol is supposed to be expedient for the treatment of inflammatory diseases of the respiratory organs caused by lincomycin sensitive flora.


Investigating language lateralization during phonological and semantic fluency tasks using functional transcranial Doppler sonography.
Although there is consensus that the left hemisphere plays a critical role in language processing, some questions remain. Here we examine the influence of overt versus covert speech production on lateralization, the relationship between lateralization and behavioural measures of language performance and the strength of lateralization across the subcomponents of language. The present study used functional transcranial Doppler sonography (fTCD) to investigate lateralization of phonological and semantic fluency during both overt and covert word generation in right-handed adults. The laterality index (LI) was left lateralized in all conditions, and there was no difference in the strength of LI between overt and covert speech. This supports the validity of using overt speech in fTCD studies, another benefit of which is a reliable measure of speech production.


Fertilizability of ova ovulated and recovered from rabbit ovaries perfused in vitro.
Ovaries removed from New Zealand White rabbits were perfused and exposed to gonadotropin in vitro. The ova ovulated in vitro (N = 56) were recovered and cultured and then transferred to the oviducts of six previously mated Dutch Belted hosts. Twelve of the resulting 36 offspring (33.3 percent) were white. In control matings between 12 Dutch Belted females (six randomly selected and the six hosts) and New Zealand White males, only one of 80 (1.2 percent) offspring was white. These data indicate that ova ovulated in vitro can be transferred to the oviduct of a host rabbit where they may be fertilized and after implantation may develop into viable embryos.


Use of (all-blood) miniplegia versus crystalloid cardioplegia in an experimental model of acute myocardial ischemia.
Several methods of myocardial protection have been used. The use of all-blood solutions modified with glutamate and aspartate has increased. Its use in situations of acute ischemia provides improved contractile function, "resuscitating" the previously lesioned muscle. The dilution preconized by literature is around 25% of the hematocrit. The present study evaluates an all-blood cardioplegia solution with tepid 1% dilution, denominated miniplegia. Pigs of the Large-White breed were used with an isolated heart and perfused with blood of a support animal. Three groups (n = 7 per group) were designated with the following treatments: Control group (CO), St. Thomas solution (ST), continuous normothermic all-blood solutions (SG). After the stabilization period, systolic pressure (PS), diastolic pressure (PD), developed pressure (PD), stress of the wall, elastance, and passive stiffness were recorded. The hearts were submitted to 30 minutes of regional ischemia with the clamping of the anterior interventricular artery, and subsequently to 90 minutes of global ischemia with the use of the three different treatments during this period. At the beginning of global ischemia, the coronary clamp was removed. The hearts were again reperfused. Upon three minutes into reperfusion the hearts were defibrillated when necessary. Measurements were taken every 30 minutes to 90 minutes into reperfusion. The SG presented a better recovery of the ventricular function in several of the parameters recorded. The ST group was inferior to the SG group, which in turn was superior to the CO group in some of the parameters analyzed. A higher number of defibrillations were needed to reestablish coordinated heart beats in the ST and CO groups. There were no differences related to the percentage of wet weight between the SG and ST groups, and the percentage was higher in the CO group. The use of all-blood miniplegia provided superior protection when compared to global ischemia or crystalloid cardioplegia in acutely ischemic hearts. The model employed is very close to the clinical situation due to the use of blood as a perfusate.


[Study of 1,000 patients with disequilibrium].
We present a series of one thousand patients tested with electronystagmography (ENG) for evaluation of complaints of unstability. Personal data and electronystagmographic results are analysed.


Advances in endoscopic disc and spine surgery: foraminal approach.
Endoscopic spine surgery is evolving rapidly due to improvements in surgical technique, endoscope design, and instrumentation. The current technique expands on the basic features and principles of Kambin's access to the spine through the triangular zone. A standardized method for foraminal surgery, the Yeung Endoscopic Spine System (YESS) (Richard Wolf Surgical Instrument Company, Vernon Hills, Illinois, USA) technique is proposed: (1) A protocol for optimal instrument placement by identifying the skin window, annular window, anatomic disc center, and disc inclination plane through topographical coordinates calculated by lines drawn on the skin from the C-Arm image. Adjustments in the trajectory are made to accommodate individual anatomic considerations and the pathologic disorders to be accessed. (2) Evocative Chromo-Discography (Richard Wolf Surgical Instrument Company, Vernon Hills, Illinois, USA). (3) Selective Endoscopic Discectomy (Richard Wolf Surgical Instrument Company, Vernon Hills, Illinois, USA). (4) Thermal discoplasty and annuloplasty. (5) Endoscopic foraminoplasty. (6) Accessing the epidural space in the axilla between the traversing and exiting nerve root. (7) Partially resecting the posterior annulus to get beneath the herniated fragment, if needed. This technique allows access to the epidural space from the lumbar disc as far cephalad as the middle of the vertebral body or approximately 2-3 mm caudally. The foraminal approach is routinely accessible from T-10 to L4-5. L5-S1 can be accessed with special techniques that include foraminoplasty of the lateral facet. Surgical results continue to improve, consistent with refinement of indications and techniques for specific conditions treatable by this endoscopic method.


Construction of a 3-D atlas of corneal shape.
A methodology is proposed to build population-based average three dimensional (3-D) atlases or standards of the human cornea based on topographic data, along with variation maps. Also, methodologies for comparing populations or screening populations, based on these atlases are proposed. Topographies (Orbscan II; Bausch & Lomb, Rochester, NY) of 516 normal subjects were used. Methodology for the construction of a corneal atlas consisted of (1) data acquisition from both anterior and posterior corneal surfaces in the format of a 101 x 101 grid of z elevations evenly spaced (every 0.1 mm) along the x and y axes; (2) spatial normalization of the topographies on a unique average best-fit sphere to reduce the large variability in size and spatial location between corneas; (3) generation of the average 3-D model; and (4) statistics maps including average, median, and SD for each point of the grid. To demonstrate the informative potential of this methodology, examples of atlases were generated. Numerical corneal atlases allow (1) characterization of a population, (2) comparison of two or more populations, (3) comparison of an individual with a reference population, and (4) screening of a population for the detection of specific corneal shape abnormalities, such as keratoconus or previous refractive surgery. The concept of a 3-D corneal atlas was developed. The proposed technique was meant to be simple, accurate, reliable, and robust and can be extended easily to any type of topographer capable of providing tridimensional corneal maps.


EEG-Based Attention Tracking During Distracted Driving.
Distracted driving might lead to many catastrophic consequences. Developing a countermeasure to track drivers' focus of attention (FOA) and engagement of operators in dual (multi)-tasking conditions is thus imperative. Ten healthy volunteers participated in a dual-task experiment that comprised two tasks: a lane-keeping driving task and a mathematical problem-solving task (e.g., 24+15=37?) during which their electroencephalogram (EEG) and behaviors were concurrently recorded. Independent component analysis (ICA) was employed as a spatial filter to separate the contributions of independent sources from the recorded EEG data. The power spectra of six components (i.e., frontal, central, parietal, occipital, left motor, and right motor) extracted from single-task conditions were fed into support vector machine (SVM) based on the radial basis function (RBF) kernel to build an FOA assessment system. The system achieved 84.6±5.8% and 86.2±5.4% classification accuracies in detecting the participants' FOAs on the math versus driving tasks, respectively. This FOA assessment system was then applied to evaluate participants' FOAs during dual-task conditions. The detected FOAs revealed that participants' cognitive attention and strategies dynamically changed between tasks to optimize the overall performance, as attention was limited and competed. The empirical results of this study demonstrate the feasibility of a practical system to continuously estimating cognitive attention through EEG spectra.


Regulation of cell surface transferrin receptor-2 by iron-dependent cleavage and release of a soluble form.
Transferrin receptor-2 is a transmembrane protein whose expression is restricted to hepatocytes and erythroid cells. Transferrin receptor-2 has a regulatory function in iron homeostasis, since its inactivation causes systemic iron overload. Hepatic transferrin receptor-2 participates in iron sensing and is involved in hepcidin activation, although the mechanism remains unclear. Erythroid transferrin receptor-2 associates with and stabilizes erythropoietin receptors on the erythroblast surface and is essential to control erythrocyte production in iron deficiency. We identified a soluble form of transferrin receptor-2 in the media of transfected cells and showed that cultured human erythroid cells release an endogenous soluble form. Soluble transferrin receptor-2 originates from a cleavage of the cell surface protein, which is inhibited by diferric transferrin in a dose-dependent manner. Accordingly, the shedding of the transferrin receptor-2 variant G679A, mutated in the Arginine-Glycine-Aspartic acid motif and unable to bind diferric transferrin, is not modulated by the ligand. This observation links the process of transferrin receptor-2 removal from the plasma membrane to iron homeostasis. Soluble transferrin receptor-2 does not affect the binding of erythropoietin to erythropoietin receptor or the consequent signaling and partially inhibits hepcidin promoter activation only in vitro. Whether it is a component of the signals released by erythropoiesis in iron deficiency remains to be investigated. Our results indicate that membrane transferrin receptor-2, a sensor of circulating iron, is released from the cell membrane in iron deficiency.


Multivariate autoregressive models for classification of spontaneous electroencephalographic signals during mental tasks.
This article explores the use of scalar and multivariate autoregressive (AR) models to extract features from the human electroencephalogram (EEG) with which mental tasks can be discriminated. This is part of a larger project to investigate the feasibility of using EEG to allow paralyzed persons to control a device such as a wheelchair. EEG signals from four subjects were recorded while they performed two mental tasks. Quarter-second windows of six-channel EEG were transformed into four different representations: scalar AR model coefficients, multivariate AR coefficients, eigenvalues of a correlation matrix, and the Karhunen-Loève transform of the multivariate AR coefficients. Feature vectors defined by these representations were classified with a standard, feedforward neural network trained via the error backpropagation algorithm. The four representations produced similar results, with the multivariate AR coefficients performing slightly better and more consistently with an average classification accuracy of 91.4% on novel, untrained, EEG signals.


The impact of vitamin D status on the relative increase in fibroblast growth factor 23 and parathyroid hormone in chronic kidney disease.
Fibroblast growth factor (FGF) 23 is an important regulator of phosphaturia. Its serum level was found to increase before that of parathyroid hormone (PTH) in early chronic kidney disease (CKD) in some but not all previous studies. As vitamin D insufficiency is associated with elevated PTH, we determined the effect of vitamin D status on FGF23 and PTH levels in relation to glomerular filtration rate (GFR) in people with CKD stage 3. Serum intact FGF23, PTH, and 25(OH)vitamin D3 were measured in 1664 patients who were prospectively recruited from primary care. Mean or median values for key variables were an age of 73 years, estimated GFR (eGFR) of 53 ml/min per 1.73 m(2), PTH 46 pg/ml, FGF23 42 pg/ml, and 25(OH)vitamin D3 53 nmol/l. FGF23 and PTH concentrations were elevated in similar proportions of people with lower eGFR in the whole cohort. However, when 752 people with vitamin D insufficiency or deficiency were excluded, FGF23 was elevated in a greater proportion than PTH at all levels of eGFR. Conversely, among people with vitamin D insufficiency, PTH was elevated in a greater proportion than FGF23 at all GFR levels of ⩾40 ml/min per 1.73 m(2). In this cohort, we were able to triangulate the relationship between 25(OH)vitamin D3, PTH, and FGF23, showing that vitamin D status critically determines whether FGF23 or PTH becomes elevated first in the context of lower GFR. Future studies of FGF23 in people with CKD should routinely determine their vitamin D status.


Postoperative atrial fibrillation after cesarean delivery.
Atrial fibrillation (AF) is the most common arrhythmia seen clinically. Due to the lack of literature and guidelines on maternal AF as a postoperative complication following cesarean delivery (CD), we undertook a study to characterize parturients who developed AF following CD and to evaluate arrhythmia management and outcomes in this patient population. After receiving ethics committee approval, a retrospective chart review was performed to determine the incidence, possible risk factors, treatment, and outcome of women who developed AF following CD performed between 2003 and 2012 at New York Methodist Hospital in Brooklyn, New York. A total of 17,039 CDs were performed at New York Methodist Hospital from 2003 to 2012. Of these, seven parturients developed AF after CD. The incidence of AF following CD in this patient population was 1:2,434 (0.04%). The age range was 26-41 years, with a median of 33 years. All 7 parturients were at term or postterm. Two deliveries were elective and five were emergent. Two of the seven parturients had prior history of paroxysmal AF. One patient was identified as having mitral regurgitation. All seven had low levels of serum magnesium postoperatively. Out of the seven, two parturients had spontaneous conversion to normal sinus rhythm, one required electrical cardioversion and four required pharmacologic cardioversion. Postoperative AF (POAF) exists as a rare complication in women who undergo CD with an incidence of 0.04% in our patient population. All parturients in our study were noted to have hypomagnesemia in the postoperative period. Occurrence of AF increased length of hospital stay and utilization of hospital resources.


[Gut microbiota may influence childhood and adolescent onset obesity].
Childhood and adolescent onset obesity has reached epidemical proportions worldwide. Recent evidence suggests that obesity is associated with phylogenetic changes in the gut microbiota, which could potentially reveal new avenues for obesity prevention and treatment. A vast number of variables are influencing the gut microbial ecology and though many are proposed, the exact physiological processes behind the relationship are yet to be revealed. This review is focusing on recent advances addressing the potential role of the human gut microbiota in childhood and adolescent onset obesity.


Prenatal influences on bone health in children.
Optimising bone health might reduce the burden of both fractures in childhood and fragility fractures in later life. A number of maternal dietary and non-dietary factors have been identified that might influence offspring bone health and represent targets for intervention. This article will outline the accrual of bone mineral throughout the life course and how observational and intervention studies have shown that maternal diet, in particular maternal calcium and 25-hydroxyvitamin D [25(OH)D] status, and lifestyle are associated with offspring bone mineralization. Studies examining the effects of maternal micronutrient supplementation on offspring bone mineral density (BMD) will also be discussed. There is a wealth of observational evidence relating maternal diet to offspring BMD. However, high quality randomized controlled trials, such as the ongoing MAVIDOS study, are needed before these findings can be definitively translated into public health advice.


Subdeltoid lipoma causing shoulder impingement syndrome - a case report.
The impingement syndrome is defined by the compression of the rotator cuff tendons against the coracoacromial arch. Several factors contribute to this condition and they are classified as structural or functional factors. The former are changes in the coracoacromial arch, proximal humerus, bursa and rotator cuff, and the latter are related to the mechanism of the upper limb by means of synchronized activity and balanced between the rotator cuff and scapular girdle muscles. The authors report here a case of parosteal lipoma of the proximal humerus, located between the muscles deltoid, teres minor and infraspinatus causing clinical signs of impingement. It is a rare occurrence, characterized as a structural cause for the onset of this symptom.


Retrospective dose assessment for the population living in areas of local fallout from the Semipalatinsk Nuclear Test Site Part II: Internal exposure to thyroid.
A methodology to assess internal exposure to thyroid from radioiodines for the residents living in settlements located in the vicinity of the Semipalatinsk Nuclear Test Site is described that is the result of many years of research, primarily at the Moscow Institute of Biophysics. This methodology introduces two important concepts. First, the biologically active fraction, is defined as the fraction of the total activity on fallout particles with diameter less than 50 microns. That fraction is retained by vegetation and will ultimately result in contamination of dairy products. Second, the relative distance is derived as a dimensionless quantity from information on test yield, maximum height of cloud, and average wind velocity and describes how the biologically active fraction is distributed with distance from the site of the explosion. The parameter is derived in such a way that at locations with equal values of relative distance, the biologically active fraction will be the same for any test. The estimates of internal exposure to thyroid for the residents of Dolon and Kanonerka villages, for which the external exposure were assessed and given in a companion paper (Gordeev et al. 2006) in this conference, are presented. The main sources of uncertainty in the estimates are identified.


Managing Hypertension, Diabetes, and Cardiovascular Disease Risk via Short-Term Medical Trips: A Retrospective Longitudinal Study in Santo Domingo.
Short-term medical trips (STMTs) from high-resource countries frequently provide care in low and middle-income countries. Little existing literature objectively tracks the long-term outcomes of these interventions on the receiving populations over time to assess potential benefits and to ensure no harm is being done. The purpose of this study was to objectively analyze the outcomes of a biannual STMT to Santo Domingo, Dominican Republic on hypertension (HTN), diabetes mellitus type 2 (DM2), and cardiovascular disease (CVD) risk over a five-year period (2015-2019). Data from 1655 patients was extracted from the electronic medical record. In patients who received treatment and had more than one visit, a linear mixed model was used to analyze effects on systolic blood pressure (SBP) and hemoglobin A1C (HbA1C) values over time. In patients with high CVD risk based on a non-laboratory-based assessment, provider compliance with prescribing an aspirin and statin was calculated and tracked over time. In patients with HTN who received treatment, average SBP was 148.83 mmHg (SD = 23.96) at initial visit and demonstrated no change over time (Estimate: 0.68 mmHg/year increase, p = 0.46). HbA1C data was insufficient for analysis. Treatment for patients with high CVD risk with an aspirin and statin improved from 41.46% in 2015 to 70.51% in 2019. SBP in patients with HTN treated by this STMT demonstrated no significant change over time. Possible contributing factors included patient education, access and adherence to medications, and documentation of data. Provider compliance with appropriate prescribing was high for patients with HTN and DM2 and improved over time for patients with high CVD risk, serving as an indirect measure for potential long-term benefits on these populations. All STMTs should objectively track outcomes of their interventions to assess risks and benefits to the communities being served.


Care technologies to prevent and control hemorrhage in the third stage of labor: a systematic review.
to identify evidence concerning the contribution of health technologies used to prevent and control hemorrhaging in the third stage of labor. systematic review with database searches. First, two researchers independently selected the papers and, at a second point in time, held a reconciliation meeting. The Kappa coefficient was used to assess agreement, while the Grading of Recommendations, Assessment, Development and Evaluation was adopted to assess risk of bias and classify level of evidence. in this review, 42 papers were included, 34 of which addressed product technologies, most referred to pharmacological products, while two papers addressed the use of blood transparent plastic bags collector and the contribution of birth spacing and prenatal care. The eight papers addressing process technologies included the active management of the third stage of labor, controlled cord traction, uterine massage, and educational interventions. product and process technologies presented high and moderate evidence confirmed in 61.90% of the papers. The levels of evidence confirm the contribution of technologies to prevent and control hemorrhaging. Clinical nurses should provide scientific-based care and develop protocols addressing nursing care actions.


Temporary hearing threshold shift in a harbor porpoise (Phocoena phocoena) after exposure to multiple airgun sounds.
In seismic surveys, reflected sounds from airguns are used under water to detect gas and oil below the sea floor. The airguns produce broadband high-amplitude impulsive sounds, which may cause temporary or permanent threshold shifts (TTS or PTS) in cetaceans. The magnitude of the threshold shifts and the hearing frequencies at which they occur depend on factors such as the received cumulative sound exposure level (SELcum), the number of exposures, and the frequency content of the sounds. To quantify TTS caused by airgun exposure and the subsequent hearing recovery, the hearing of a harbor porpoise was tested by means of a psychophysical technique. TTS was observed after exposure to 10 and 20 consecutive shots fired from two airguns simultaneously (SELcum: 188 and 191 dB re 1 μPa2s) with mean shot intervals of around 17 s. Although most of the airgun sounds' energy was below 1 kHz, statistically significant initial TTS1-4 (1-4 min after sound exposure stopped) of ∼4.4 dB occurred only at the hearing frequency 4 kHz, and not at lower hearing frequencies tested (0.5, 1, and 2 kHz). Recovery occurred within 12 min post-exposure. The study indicates that frequency-weighted SELcum is a good predictor for the low levels of TTS observed.


Inhibitory effect of maple syrup on the cell growth and invasion of human colorectal cancer cells.
Maple syrup is a natural sweetener consumed by individuals of all ages throughout the world. Maple syrup contains not only carbohydrates such as sucrose but also various components such as organic acids, amino acids, vitamins and phenolic compounds. Recent studies have shown that these phenolic compounds in maple syrup may possess various activities such as decreasing the blood glucose level and an anticancer effect. In this study, we examined the effect of three types of maple syrup, classified by color, on the cell proliferation, migration and invasion of colorectal cancer (CRC) cells in order to investigate whether the maple syrup is suitable as a phytomedicine for cancer treatment. CRC cells that were administered maple syrup showed significantly lower growth rates than cells that were administered sucrose. In addition, administration of maple syrup to CRC cells caused inhibition of cell invasion, while there was no effect on cell migration. Administration of maple syrup clearly inhibited AKT phosphorylation, while there was no effect on ERK phosphorylation. These data suggest that maple syrup might inhibit cell proliferation and invasion through suppression of AKT activation and be suitable as a phytomedicine for CRC treatment, with fewer adverse effects than traditional chemotherapy.


Radiation induces acute alterations in neuronal function.
Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs) from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABA(A)Rs). These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study.


Probabilistic source separation for robust electrocardiography.
Blind source separation (BSS) techniques are widely used to extract signals of interest from a mixture with other signals. These methods, however, typically lack possibilities to incorporate any prior knowledge on the mixing of the source signals. Particularly for electrocardiographic signals, knowledge on the mixing is available based on the origin and propagation properties of these signals. In this paper, a novel source separation method is developed that combines the strengths and accuracy of BSS techniques with the robustness of an underlying physiological model of the electrocardiogram (ECG). The method is developed within a probabilistic framework and yields an iterative convergence of the separation matrix towards a maximum a posteriori estimation, where in each iteration the latest estimate of the separation matrix is corrected towards the physiological model. The method is evaluated by comparing its performance to that of FastICA on both simulated and real multi-channel ECG recordings, demonstrating that the developed method outperforms FastICA in terms of extracting the ECG source signals.


Unraveling the Interfacial Structure-Performance Correlation of Flexible Metal-Organic Framework Membranes on Polymeric Substrates.
Pure metal-organic framework (MOF) layers deposited on porous supports are important candidates for molecular sieving membranes, but their performance usually deviates from theoretical estimations. Here, we combine step-wise scanning electron microscopy imaging, time-resolved synchrotron X-ray scattering, terahertz infrared spectroscopy, and density functional theory calculation to investigate the ZIF-8 membrane formation on two types (polydopamine and TiO2) of functionalized porous supports. Though molecular sieving of ZIF-8 membranes for smaller gases (He, H2, and CO2) can be achieved with both types of functionalized supports, we unravel that the strong interaction between MOF and polydopamine can disrupt the formation of "perfect" MOF crystals at the interface, leading to a "contracted" MOF structure with partially uncoordinated imidazolate ligands. This further affects the low-frequency dynamical parameters of the framework and inhibits the effective seeded growth. Eventually, it leads to an unexpected loss of selectivity for the bulkier gases (N2 and CH4) for ZIF-8 on polydopamine-functionalized supports. This work links the dynamical aspects of MOFs with their gas transport behavior and highlights the importance of regulating the interfacial weak forces to preserve the ideal molecular sieving efficiency of MOF membranes, which also provides guidance for defect engineering of MOF film fabrication for sensing and electronic devices beyond membranes.


HDAC6-induced premature chromatin compaction in mouse oocytes and fertilised eggs.
Chromatin remodelling in the fertilised mouse egg is intimately linked to protein synthesis and degradation, to protamine by histone replacement and to specific histone modifications. The involvement of histone deacetylases (HDACs) in the beginning of development is poorly understood. HDACs are essential for cell proliferation and in the control of gene expression in a wide variety of mammalian systems. Here we focus on mHDAC6, a recently identified class II histone deacetylase, and we analyse its expression and localisation in oocytes and pronuclear zygotes. By indirect immunofluorescence we show that mHDAC6 is detected in the cytoplasm of germinal vesicle (GV) stage oocytes and 1-cell embryos. Ectopic expression of this enzyme after injection into germinal vesicles and pronuclei alters the nuclear structure and causes premature compaction of the chromatin. Our data suggest that the effect of condensation is linked to the ubiquitin-binding activity of mHDAC6, rather than to its function as a deacetylase.


A method for the purification of milligram quantities of stable human phosphatidylcholine-cholesterol acyltransferase.
A method for processing 3 litres of human plasma for the purification of phosphatidylcholine-cholesterol acyltransferase is described. The method involves (NH4)2SO4 fractionation, citric acid treatment, and DEAE-cellulose and hydroxyapatite chromatography. At this stage the enzyme preparation is purified approx. 8000-fold. This preparation appears to be free of lipoproteins as determined by immunoelectrophoresis against anti-human serum and is minimally contaminated with albumin (less than 30 mug/mg of enzyme protein) as determined by immunodiffusion. The activity of the enzyme was stable for 4 days, but most of its activity was lost after 20 days On electrophoresis on 5% polyacrylamide gel, a fast-moving band with enzyme activity and a slow-moving band with no enzyme activity was observed. A faint band of albumin was also present. Extracts of enzymically active bands cut from ten gels and then pooled and extracted with 0.15 M-NaC1/4mM-sodium phosphate, pH 7.0, showed a single band on re-electrophoresis on 5% polyacrylamide gel.


Rapid detection of rifampin resistance in Mycobacterium tuberculosis isolates from India and Mexico by a molecular beacon assay.
We assessed the performance of a rapid, single-well, real-time PCR assay for the detection of rifampin-resistant Mycobacterium tuberculosis by using clinical isolates from north India and Mexico, regions with a high incidence of tuberculosis. The assay uses five differently colored molecular beacons to determine if a short region of the M. tuberculosis rpoB gene contains mutations that predict rifampin resistance in most isolates. Until now, the assay had not been sufficiently tested on samples from countries with a high incidence of tuberculosis. In the present study, the assay detected mutations in 16 out of 16 rifampin-resistant isolates from north India (100%) and in 55 of 64 rifampin-resistant isolates from Mexico (86%) compared to results with standard susceptibility testing. The assay did not detect mutations (a finding predictive of rifampin susceptibility) in 37 out of 37 rifampin-susceptible isolates from India (100%) and 125 out of 126 rifampin-susceptible isolates from Mexico (99%). DNA sequencing revealed that none of the nine rifampin-resistant isolates from Mexico, which were misidentified as rifampin susceptible by the molecular beacon assay, contained a mutation in the region targeted by the molecular beacons. The one rifampin-susceptible isolate from Mexico that appeared to be rifampin resistant by the molecular beacon assay contained an S531W mutation, which is usually associated with rifampin resistance. Of the rifampin-resistant isolates that were correctly identified in the molecular beacon assay, one contained a novel L530A mutation and another contained a novel deletion between codons 511 and 514. Overall, the molecular beacon assay appears to have sufficient sensitivity (89%) and specificity (99%) for use in countries with a high prevalence of tuberculosis.


Putative channel components for the fast-rotating sodium-driven flagellar motor of a marine bacterium.
The polar flagellum of Vibrio alginolyticus rotates remarkably fast (up to 1,700 revolutions per second) by using a motor driven by sodium ions. Two genes, motX and motY, for the sodium-driven flagellar motor have been identified in marine bacteria, Vibrio parahaemolyticus and V. alginolyticus. They have no similarity to the genes for proton-driven motors, motA and motB, whose products constitute a proton channel. MotX was proposed to be a component of a sodium channel. Here we identified additional sodium motor genes, pomA and pomB, in V. alginolyticus. Unexpectedly, PomA and PomB have similarities to MotA and MotB, respectively, especially in the predicted transmembrane regions. These results suggest that PomA and PomB may be sodium-conducting channel components of the sodium-driven motor and that the motor part consists of the products of at least four genes, pomA, pomB, motX, and motY. Furthermore, swimming speed was controlled by the expression level of the pomA gene, suggesting that newly synthesized PomA proteins, which are components of a force-generating unit, were successively integrated into the defective motor complexes. These findings imply that Na+-driven flagellar motors may have similar structure and function as proton-driven motors, but with some interesting differences as well, and it is possible to compare and study the coupling mechanisms of the sodium and proton ion flux for the force generation.


Translation, Cultural Adaptation and Validation of the Hill Bone Compliance to High Blood Pressure Therapy Scale to Nepalese Language.
Control of high blood pressure and prevention of cardiovascular complications among hypertensive patients depends on patients' adherence to therapy. The Hill-Bone Compliance to High Blood Pressure Therapy Scale (HBCTS) is one of the most popular scale to assess hypertensive patients' adherence behaviour. Unfortunately, no questionnaire in the Nepalese language is available to date to assess adherence to anti-hypertensive therapy. To translate, culturally adapt and validate the English original version of the HBCTS into Nepalese language to measure treatment adherence of Nepalese hypertensive patients. The cross-sectional study was conducted to translate, culturally adapt and validate the HBCTS into Nepalese version. The standard translation process was followed and was evaluated among 282 hypertensive patients visiting selected primary healthcare centers (PHCCs) of Kathmandu district, Nepal. Cronbach's alpha was measured to assess the reliability of the tool. Exploratory factor analysis using principal component analysis with varimax rotation was used to evaluate structural validity. The mean±SD age of 282 participants was 58.49±12.44 years. Majority of participants were literate (75.2%), and consumed at least one anti-hypertensive medication per day (85.5%). Nearly half (42.2%) of the participants had a family history of hypertension, and almost half (48%) of them had comorbid conditions. Mean ±SD score for overall adherence was 17.85±3.87 while those of medication taking, reduced salt taking, and appointment keeping subscales were 10.63±2.55, 4.16±1.12 and 3.06±1.07, respectively. Kaiser Meyer Olkin (KMO) was found to be 0.877. Exploratory factor analysis revealed a three-component structure; however, the loading of components into medication adherence, reduced salt intake and appointment keeping constructs were not identical to the original tool. Cronbach's alpha score for the entire HBCTS scale was 0.846. The translated Nepali version of the HBCTS demonstrated acceptable reliability and validity to measure adherence to antihypertensive therapy among hypertensive patients in clinical and community settings in Nepal.


Genotyping of alpha-antitrypsin in ten Croatian families.
The aims of the study were to determine alpha-antitrypsin (AAT) genotype by a simple DNA-based method and to investigate the association of AAT genotype and serum AAT concentration in a group of ten families. AAT genotype was determined by PCR-RFLP and serum concentration by radial immunodiffusion in samples from each member of ten families (mother, father, and child/children). In the group of parents, five normal genotypes, Pi MM, with a normal serum AAT concentration, and fifteen Pi MZ genotypes, four of them with slightly decreased (43%-66% of the mean) AAT concentration were detected. In the group of children, particular genotypes followed the mode of inheritance. There were eight Pi MZ, three of them with slightly decreased (52%-60% of the mean) AAT concentration, and five Pi ZZ genotypes with considerably decreased (24%-45% of the mean) AAT concentration. PCR-RFLP is the method of choice for AAT genotyping. AAT concentration is not a reliable biochemical marker of AAT deficiency. Determination of AAT genotype in family studies allows the risk of deficient allele inheritance to be followed up and assessed. Early diagnosis of a deficient AAT genotype contributes to the success of currently widely available AAT replacement therapy.


Intravenous immunoglobulin for multifocal motor neuropathy.
Multifocal motor neuropathy is a rare, probably immune mediated disorder characterised by slowly progressive, asymmetric, distal weakness of one or more limbs with no objective loss of sensation. It may cause prolonged periods of disability. The treatment options for multifocal motor neuropathy are sparse. Patients with multifocal motor neuropathy do not usually respond to steroids or plasma exchange, and may even worsen with these treatments. Many uncontrolled studies have suggested a beneficial effect of intravenous immunoglobulin. To review systematically the evidence from randomised controlled trials concerning the efficacy and safety of intravenous immunoglobulin in multifocal motor neuropathy. We used the search strategy of the Cochrane Neuromuscular Disease Review Group to search the Disease Group register (searched September 2003), MEDLINE (January 1990 to September 2003), EMBASE (January 1990 to September 2003) and ISI (January 1990 to September 2003) databases for randomised controlled trials. Randomised controlled studies examining the effects of any dose of intravenous immunoglobulin versus placebo in patients with definite or probable multifocal motor neuropathy. Outcome measures had to include one of the following: disability, strength, or conduction block. Studies which reported the frequency of adverse effects were used to assess safety. Two authors reviewed literature searches to identify potentially relevant trials, scored their quality and extracted data independently. For dichotomous data, we calculated relative risks, and for continuous data, effect sizes and weighted pooled effect sizes. Statistical uncertainty was expressed with 95% confidence intervals. Four randomised controlled trials including a total of 34 patients were suitable for this systematic review. Strength improved in 78% of patients treated with intravenous immunoglobulin and only 4% of placebo-treated patients. Disability improved in 39% of patients after intravenous immunoglobulin treatment and in 11% after placebo (statistically not significantly different). Mild, transient side effects were reported in 71% of intravenous immunoglobulin treated patients. Serious side effects were not encountered. Limited evidence from randomised controlled trials shows that intravenous immunoglobulin has a beneficial effect on strength. There was a non-significant trend towards improvement in disability. More research is needed to discover whether intravenous immunoglobulin improves disability and is cost-effective.


Accelerometer- versus questionnaire-based assessment of physical activity and their changes over time in patients with COPD.
Physical activity (PA) is an important outcome parameter in patients with COPD regarding hospitalizations and mortality. Both objective assessment by accelerometers and self-evaluation by questionnaires were used in studies investigating PA in COPD. Whether self-reported questionnaires can adequately reflect PA and its changes over time compared to objective assessments has not been thoroughly investigated in COPD. In this COPD cohort study, we evaluated whether PA measured by accelerometer and its annual changes can also be assessed by self-reported questionnaires. In 178 COPD patients with at least two assessments of PA, the agreement between objectively measured and self-reported activity was analyzed by Bland-Altman plots. Daily PA was assessed by a triaxial activity monitor over 1 week and by the self-reported German PA questionnaire 50+. Comparison between the two methods of measurement revealed no convincing agreement with a mean difference and limits of agreement (±1.96 standard deviation [SD]) of time spent in at least moderate PA (>3 metabolic equivalent of task [MET]) of -77.6 (-340.3/185.2) min/day, indicating a self-reported overestimation of PA by the questionnaire. The mean difference and limits of agreement (±1.96SD) in the annual change of PA was 1.2 min/day (-208.2/282.6 min/day), showing also a poor agreement on an individual level. Evaluation of objectively measured and self-reported PA and their annual changes revealed no agreement in patients with COPD. Therefore, the evaluated questionnaire seems not helpful for measurement of PA and its changes over time.


Binding of [3H]batrachotoxinin A benzoate to specific sites on rat cardiac sodium channels.
Radiolabeled neurotoxins have been used to study the structure and function of sodium channels. We studied the binding of [3H] batrachotoxinin A 20 alpha-benzoate [( 3H]BTX-B) to specific sites on sodium channels on rat cardiac myocytes. Calcium-tolerant myocytes were prepared by collagenase dispersion of adult rat hearts and were 75-83% viable. As with the nerve channel, specific binding of [3H]BTX-B to its receptor site was seen only in the presence of sea anemone toxin (ATX). The affinity of ATX for its binding sites may be estimated from its concentration-dependent stimulatory effect on [3H]BTX-B binding. These results suggest that, in the presence of 5.4 mM KCl, the myocytes have two affinities for ATX with estimated dissociation constants of 0.52 microM and 12.9 microM. Depolarization of the myocytes with either 65 mM KCl or 0.1 mM BaCl2 results in the loss of the 0.52 microM component, suggesting that it is voltage sensitive. The 0.52 microM and 12.9 microM components have maximal binding capacities corresponding to 4 and 11 sites/micron 2 of myocyte surface area, respectively. Scatchard analysis of [3H]BTX-B binding in the presence of ATX demonstrates a single class of sites with a KD of 25-35 nM. These results demonstrate that [3H]BTX-B can be used as a radioligand probe of the adult rat sodium channel and will facilitate a biochemical approach to the study of the interaction between antiarrhythmic drugs and the sodium channel.


Deletions and single base pair changes in the yeast mating type locus that prevent homothallic mating type conversions.
Several cis-acting mutations that prevent homothallic mating type conversions in Saccharomyces cerevisiae have been examined. Deletions within the mating type (MAT) locus were obtained by selecting for survivors among homothallic MAT alpha cells carrying the rad52 mutation. The survivors were unable to switch mating type, even in RAD+ derivatives. The deletions varied in size from fewer than 50 to more than 750 base pairs. All of the deletions removed a Hha I site at the border between the alpha-specific sequences (Y alpha) and the adjacent Z region. We also examined several spontaneous inc mutations that prevent MAT switching. Two of these mutations were cloned in recombinant DNA plasmids and their sequences were determined. The MAT alpha-inc 3-7 mutation proved to have an altered Hha I site at the Y alpha/Z border, by virtue of a single base pair substitution G . C leads to A . T in the second base pair of the Z region (Z2). Restriction fragment analysis showed that two other independently isolated strains with MAT alpha-inc mutations had altered the same Hha I site. The MAT a-inc 4-28 mutation contains a single base pair substitution C . G leads to T . A at position Z6. A base pair difference at position Z11 in two MATa strains does not affect MATa conversions. We conclude that the region near the Y/Z border is essential for the efficient switching of MAT alleles and constitutes an enzyme recognition site for a specific nucleolytic cleavage of MAT DNA.


Cellulase activity screening using pure carboxymethylcellulose: application to soluble cellulolytic samples and to plant tissue prints.
Reliable, rapid and inexpensive detection of cellulolytic enzymes that can be used for a wide variety of biological and environmental samples are currently in high demand. Here, a new cellulase detection protocol is described that circumvents problems observed with popular agar-based methods by exploiting the ability of carboxymethylcellulose (CMC) to form gel-like surfaces on its own. These pure CMC-layers are sensitive to cellulolytic degradation and stainable by Gram's iodine without showing unwelcome reactions with other enzymes. The staining intensity negatively correlates with the enzyme activity and can be used for quantification. Cellulase activities are not obstructed by high sugar contents (e.g., in plant material) which limit the applicability of other quantification methods, making our new method particularly attractive for screening of plant extracts. A useful variant of this new method is its applicability to plant tissue prints for spatial mapping of the cellulolytic activity in a zymogram-like fashion.


Clues to the electrocardiographic diagnosis of subtle Wolff-Parkinson-White syndrome in children.
The electrocardiographic diagnosis of Wolff-Parkinson-White syndrome (WPW) may be missed because delta waves can be subtle in children, so we examined 66 electrocardiograms from patients with proven WPW, 24 from those with questionable WPW ("subtle WPW"), and 369 consecutive electrocardiograms from control patients to identify additional clues that WPW might be present. Three features were notable in WPW: no Q wave in left chest leads (88%), PR interval less than 100 milliseconds (80%), and left axis deviation (33%). In subtle WPW these findings were similar: 79%, 67%, and 46%, respectively. By comparison, 5% of control subjects had no Q wave, 16% had a PR interval of less than 100 milliseconds, and 4% had left axis deviation (all p less than 0.001). The coexistence of two of these features was common (74%) in WPW and subtle WPW (63%) but rare (2%) in control subjects (p less than 0.001). A PR interval of less than 100 milliseconds was less specific before 1 year of age, but 89% of patients with WPW had a QRS duration of greater than 80 milliseconds versus 2% of control subjects (p less than 0.001). Obvious WPW disappeared later in 11 patients; however, left axis deviation or lack of a Q wave persisted in eight (p less than 0.01). We conclude that the diagnosis of WPW in children, even when subtle, is suggested by the presence of these four changes. Preexcitation may persist in some patients in whom overt delta waves are no longer present.


Efficacy of abdominal acupuncture for neck pain: A randomized controlled trial.
This study aims to provide evidence regarding the clinical efficacy of abdominal acupuncture for neck pain. This randomized, patient and assessor-blind, sham-controlled trial was conducted at a Chinese medicine center in Hong Kong between November 2014 and March 2016. A total of 154 eligible participants (age range, 18-65 years) with neck pain were randomly assigned to receive abdominal (n = 77) or non-penetrating sham abdominal (sham group; n = 77) acupuncture. Each participant was administered treatment over six sessions by Registered Chinese Medicine Practitioners, in accordance with a standardized protocol. The primary outcome was mean improvement in neck pain disability scores evaluated by the Northwick Park Neck Pain Questionnaire (NPQ). Secondary outcomes included intensity of neck pain and health-related quality-of-life measures. The outcomes were assessed at baseline and at 2 and 6 weeks from baseline. Patients in the abdominal acupuncture group received additional follow-up evaluation at 14 weeks from baseline. Outcomes were evaluated by intention-to-treat analysis. All participants provided informed consent for treatment and follow-up evaluation. Patients who received abdominal acupuncture exhibited greater improvement in NPQ scores than those who received sham treatment at both 2 and 6 weeks from baseline (intergroup mean differences, -5.75; 95% confidence interval [CI], -9.48 to -2.03; P = 0.008 and -8.65; 95% CI, -12.13 to -5.16; P < 0.001, respectively). The improvement in NPQ scores in the abdominal acupuncture group was even more significant at 14 weeks from baseline. Patients in the abdominal acupuncture group also exhibited significantly greater improvements in intensity of neck pain and a few quality-of-life measures than those in the sham abdominal acupuncture group, without any serious adverse events. These findings suggest that abdominal acupuncture is an effective alternative treatment for neck pain. Chinese Clinical Trial Registry ChiCTR-TRC-14004932.


Intramural hematomas of the gastrointestinal system: a 5-year single center experience.
Although spontaneous intramural hematomas of the gastrointestinal tract are very rare, they may be observed with the use of oral anticoagulant, though less frequently in cases of hematological malignancy and other bleeding disorders. Cases diagnosed as spontaneous intramural hematoma have been assessed in our clinic. The cases, which were diagnosed as spontaneous intramural hematoma in the gastrointestinal tract (SIHGT) following anamnesis, physical examination, biochemical, radiological and endoscopic findings from July 2008 to July 2012, have been assessed retrospectively. Seven out of 13 cases were women and the mean age was 65.1 years (34 to 82 years). The most frequent complaint on admission was abdominal pain. The most frequent location of SIHGT was the ileum (n = 8). Oral anticoagulant use was the most common cause of etiology (n = 12). In 10 cases, International normalized ratio values were higher than treatment range (2 to 3, where mechanical valve replacement was 2.5 to 3.5) and mean value was 7.6 (1.70 to 23.13). While 12 cases were discharged without problems with medical treatment, one case with acute myeloid leukemia died in the intensive care unit following cerebrovascular attack. Spontaneus bleeding and hematomas that may arise in connection with bleeding diathesis may be fatal in cases with long-term oral anticoagulant treatment and insufficient follow-up. In management of these cases, it may be necessary to arrange conservative follow up and/or initialize low molecular weight heparin, and administer vitamin K as well as replace blood products and coagulation factors when indicated.


[State of microcirculation and cellular hemostasis in men with borderline arterial hypertension during thermoneutral "dry" water immersion].
Platelet hemostasis, microcirculation, blood viscosity and lipid metabolism were examined in 18 men with borderline hypertension and 8 healthy men before, during and after 7-day immersion. The exposure to thermoneutral dry water immersion produced hypercoagulopathic changes of platelet hemostasis in the healthy and hypertensive subjects. Platelet hemostasis returned to the pretest level in the healthy subjects 2 days and in the hypertensive subjects only 5 days after exposure. Prior to immersion the hypertensive subjects showed signs of capillarotrophic insufficiency which increased after exposure. On immersion day 3 the hypertensive subjects exhibited a higher blood viscosity and a larger content of total lipids and free fatty acids. All the parameters returned to normal 2 days after immersion.