Subjective effects as predictors of substance use disorders in a clinical sample: A longitudinal study.
The literature on the association between subjective effects (SEs; i.e., how an individual perceives their physiological and psychological reactions to a drug) and substance use disorders (SUDs) is largely limited to community samples. The present study addressed the following aims in a clinical sample: whether SEs predict general versus substance-specific SUD in adolescence and adulthood after controlling for conduct disorder symptoms (CDsymp); whether SEs predict SUDs across drug classes; whether SEs predict change in SUD from adolescence to adulthood; and whether there are racial/ethnic differences in associations. Longitudinal analyses were conducted using data from a sample of 744 clinical probands recruited from residential and outpatient SUD treatment facilities in CO during adolescence (Mage = 16.26) and re-assessed twice in adulthood (Mages = 22.56 and 28.96), approximately seven and twelve years after first assessment. SEs and CDsymp were assessed in adolescence. SUD severity was assessed at adolescence and twice during adulthood. SEs assessed in adolescence robustly predicted general SUD for legal and illegal substances in adolescence and adulthood, whereas CDsymp predicted SUD primarily in adolescence. Higher positive and negative SEs in adolescence were associated with greater SUD severity after controlling for CDsymp, with similar magnitudes. Results indicated cross-substance effects of SEs on SUD. We found no evidence for racial/ethnic differences in associations. We investigated the progression of SUD in a high-risk sample with greater odds of sustained SUD. In contrast to CDsymp, both positive and negative SEs consistently predicted general SUD across substances in adolescence and adulthood.


Sequential Y90 liver radioembolization and portal vein embolization: an additional strategy to downstage liver tumors and to enhance liver hypertrophy before major hepatectomies.
Yttrium (Y)90 liver radioembolization (TARE) induces both tumor downsizing and contralateral liver hypertrophy. In this study, we report the preliminary results of a sequential strategy combining Y90 radioembolization and portal vein embolization (PVE) before major right liver resections. We retrospectively reviewed clinical, radiological, and biological data of 5 consecutive patients undergoing Y90 TARE-PVE before major right liver resections. Comparison was made with patients undergoing PVE alone or liver venous deprivation (LVD) during the same period. Between January 2019 and September 2022, five patients underwent sequential TARE-PVE. Type of resection included the following: right hepatectomy (n = 1), right hepatectomy + 1 (n = 2), and right hepatectomy + 1 + 4 (n = 2) with no postoperative mortality. Volumetric data showed a mean hypertrophy ratio of 30.4% after TARE and an additional 37.4% after sequential PVE. Patients undergoing sequential TARE-PVE had higher hypertrophy ratio (p = 0.02; p = 0.004), hypertrophy degree (p = 0.02; p < 0.0001), shorter time to normalize bilirubin (p = 0.04), and prothrombin time (p = 0.003; p < 0.0001) compared with patients receiving LVD or PVE. Time from diagnosis to surgery was statistically significant longer in patients undergoing sequential TARE-PVE compared with LVD or PVE (293.4 ± 169.1 vs 54.18 ±18.26 vs 58.62±13.15; p = 0.0008; p = <0.0001). This preliminary report suggests that sequential PVE and TARE can represent a safe and an alternative strategy to downstage liver tumors and to enhance liver hypertrophy before major hepatectomies. When compared with PVE and LVD, sequential TARE/PVE takes longer times but achieves some advantages which warrant further evaluation in a larger setting.


Lumbosacral epidural magnesium prolongs ketamine analgesia in conscious sheep.
To determine the analgesic, motor, sedation and systemic effects of lumbosacral epidural magnesium sulphate added to ketamine in the sheep. Six healthy adult male mixed-breed sheep; weighing 43 ± 5 kg and aged 20-36 months. Each sheep underwent three treatments, at least 2 weeks apart, via epidural injection: (1) ketamine (KE; 2.5 mg/kg), (2) magnesium sulphate (MG; 100 mg), and (3) KE + MG (KEMG; 2.5 mg/kg + 100 mg, respectively). Epidural injections were administered through the lumbosacral space. Analgesia, motor block, sedation, cardiovascular effects, respiratory rate, skin temperature, and rectal temperature were evaluated before (baseline) and after drug administration as needed. The duration of analgesia with the lumbosacral epidural KEMG combination was 115 ± 17 min (mean ± SD), that is, more than twice that obtained with KE (41 ± 7 min) or MG (29 ± 5 min) alone. KE and KEMG used in this experiment induced severe ataxia. The heart rate and arterial blood pressures changes were no statistical difference in these clinically health sheep. The dose of magnesium sulphate to lumbosacral epidural ketamine in sheep is feasible, and can be used in procedures analgesics in sheep.


A new PCR-based approach for the specific amplification of DNA from different Schistosoma species applicable to human urine samples.
Currently available methods for the diagnosis of human schistosomiasis often lack enough sensitivity and specificity. Recently, several authors have developed more specific and sensitive diagnostic methods, mainly based on the polymerase chain reaction (PCR) technique. Nevertheless, these have been only applied for the diagnosis of 1 out of 4 Schistosoma species affecting man (S. mansoni). Additionally, application of specific PCR has been exclusively used for blood or faecal patients' samples. Here, we develop a new, high sensitive PCR approach that allows the genus- and species-specific amplification of the main 4 Schistosoma species causing disease in man plus S. bovis. We further successfully apply this technique for the detection of parasite DNA in easy-to-handle urine samples from patients with schistosomiasis. With these samples, we have found 94.4% sensitivity and 99.9% specificity when applying a genus-specific (Schistosoma spp.) primer pair, and 100% sensitivity and 98.9% specificity in a species-specific (S. mansoni) PCR.


CompLement C5 Antibodies for decreasing brain injury after aneurysmal Subarachnoid Haemorrhage (CLASH): study protocol for a randomised controlled phase II clinical trial.
The inflammatory response after aneurysmal subarachnoid haemorrhage (aSAH) has been associated with early brain injury, delayed cerebral ischaemia, poor functional outcome, and case fatality. In experimental SAH studies, complement C5 antibodies administered shortly after SAH reduced brain injury with approximately 40%. Complement component C5 may be a new therapeutic target to reduce brain injury and hereby improve the outcome after aSAH. We aim to investigate the pharmacodynamic efficacy and safety of eculizumab (complement C5 antibody) in patients with aSAH. A randomised, controlled, open-label, phase II clinical trial with blinded outcome assessment. Eculizumab (1200 mg) is administered intravenously < 12 h, on day 3 and on day 7 after ictus. Patients in the intervention group receive prophylactic antibiotics for 4 weeks, and those with a central line or an external ventricular shunt and a positive fungal or yeast culture also receive prophylactic antifungal therapy for 4 weeks. The primary outcome is C5a concentration in the cerebrospinal fluid (CSF) on day 3 after ictus. Secondary outcomes include the occurrence of adverse events, inflammatory parameters in the blood and CSF, cerebral infarction on magnetic resonance imaging, and clinical and cognitive outcomes. We aim to evaluate 26 patients with CSF assessments, 13 in the intervention group and 13 in the comparator group. To compensate for early case fatality and inability to obtain CSF, we will include 20 patients per group. The CLASH trial is the first trial to investigate the pharmacodynamic efficacy and safety of eculizumab in the early phase after aSAH. Netherlands Trial Register NTR6752 . Registered on 27 October 2017 European Clinical Trials Database (EudraCT) 2017-004307-51.


The mercury-sensitive residue at cysteine 189 in the CHIP28 water channel.
Water channels provide the plasma membranes of red cells and renal proximal tubules with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. Molecular identification of CHIP28 protein as the membrane water channel was first accomplished by measurement of osmotic swelling of Xenopus oocytes injected with CHIP28 RNA (Preston, G.M., Carroll, T.P., Guggino, W.B., and Agre, P. (1992) Science 256, 385-387). Since water channels are pharmacologically inhibited by submillimolar concentrations of Hg2+, site-directed mutagenesis was undertaken to demonstrate which of the 4 cysteines (87, 102, 152, or 189) is the Hg(2+)-sensitive residue in the CHIP28 molecule. Each cysteine was individually replaced by serine, and oocytes expressing each of the four mutants exhibited osmotic water permeability (Pf) equivalent to wild-type CHIP28. After incubation in HgCl2, all were significantly inhibited, except C189S exists as a multisubunit complex in the native membrane; however, although oocytes injected with mixed CHIP28 and C189S RNAs exhibited Pf corresponding to the sum of their individual activities, exposure to Hg2+ only reduced the Pf to the level of the C189S mutant. Of the six substitutions at residue 189, only the serine and alanine mutants exhibited increased Pf and had glycosylation patterns resembling wild-type CHIP28 on immunoblots. These studies demonstrated: (i) CHIP28 water channel activity is retained despite substitution of individual cysteines with serine; (ii) cysteine 189 is the Hg(2+)-sensitive residue; (iii) the subunits of the CHIP28 complex are individually active water pores; (iv) residue 189 is critical to proper processing of the CHIP28 protein.


Molecular characterization of diapause hormone and pheromone biosynthesis activating neuropeptide from the black-back prominent moth, Clostera anastomosis (L.) (Lepidoptera, Notodontidae).
Using a strategy of rapid amplification of cDNA ends, the cDNA of diapause hormone (DH) and pheromone biosynthesis activating neuropeptide (PBAN) was cloned from the head of Clostera anastomosis (L.). The Cloan-DH-PBAN cDNA contains an open reading frame encoding a 196-amino acid preprohormone, from which five putative FXPRL peptides, DH, PBAN, alpha-SGNP(SGNP, suboesophageal ganglion neuropeptide), beta-SGNP and gamma-SGNP, are released. Comparing the deduced amino acid sequences from cDNAs of these five FXPRL peptides to those known from other insects, Cloan-DH shows highest similarity of 93.1% to that from Agrotis ipsilon, Cloan-PBAN 93.9% to those from Helicoverpa armigera, Helicoverpa zea and Helicoverpa assulta, which show the highest similarity to species of Noctuidae. Phylogenetic analysis revealed that the Cloan-DH-PBAN gene is relatively closely related to those from Noctuoidea, but distant from those from Tortricoidea, Yponomeutoidea and Bombycoidea species. The DNA sequence encoding Cloan-DH-PBAN was cloned by PCR, which is 3698bp in size and comprises six exons interspersed by five introns. Developmental expression of the DH-PBAN transcripts in the head was also showed by a semi-quantitative RT-PCR method, which was relatively low in larvae and remained low in pupae of both sexes, increased sharply in adults of both sexes.


Behavioral interactions between nicotine and caffeine.
Nicotine (0.01-1.0 mg/kg) was administered alone and together with three doses of caffeine (3.0, 10.0 and 30.0 mg/kg) to rats responding on a fixed-interval 2-min schedule of food reinforcement. The effects on overall response rate depended on dose: with the 3.0 mg/kg dose of caffeine response rate was increased by an amount approximately equal to the effect of the caffeine alone, while 10.0 mg/kg of caffeine reduced and 30.0 mg/kg completely abolished the increases in response rate produced by nicotine. The within-interval pattern of responding was affected in a similar, dose-related manner by both nicotine and caffeine alone. These effects added to produce large changes in the pattern when high doses of the two drugs were co-administered. The changes comprised increases in lower response rates in the early and middle parts of the interval and proportionally smaller increases or decreases in the higher rates occurring later in the interval. The interaction between nicotine and caffeine cannot be characterized simply, but depends on the particular aspect of behavior under examination.


Photonic response and temperature evolution of SiO2/TiO2 multilayers.
The microstructural and optical reflectivity response of photonic SiO2/TiO2 nanomultilayers have been investigated as a function of temperature and up to the material system's melting point. The nanomultilayers exhibit high, broadband reflectivities up to 1350 °C with values that exceed 75% for a 1 μm broad wavelength range (600-1600 nm). The optimized nanometer sized, dielectric multilayers undergo phase transformations from anatase TiO2 and amorphous SiO2 to the thermodynamically stable phases, rutile and cristobalite, respectively, that alter their structural morphology from the initial multilayers to that of a scatterer. Nonetheless, they retain their photonic characteristics, when characterized on top of selected substrate foils. The thermal behavior of the nanometer sized multilayers has been investigated by differential thermal analysis (DTA) and compared to that of commercially available, mm-sized, annealed powders. The same melting reactions were observed, but the temperatures were lower for the nm-sized samples. The samples were characterized using X-ray powder diffraction before DTA and after annealing at temperatures of 1350 and 1700 °C. The microstructural evolution and phase compositions were investigated by scanning electron microscopy and energy-dispersive X-ray spectroscopy measurements. The limited mutual solubility of one material to another, in combination with the preservation of their optical reflectivity response even after annealing, makes them an interesting material system for high-temperature, photonic coatings, such as photovoltaics, aerospace re-entry and gas turbines, where ultra-high temperatures and intense thermal radiation are present. The online version contains supplementary material available at 10.1007/s10853-021-06557-y.


Ultrastructural detection of DNA fragmentation in myonuclei of fatal reducing body myopathy.
Muscle biopsy specimens of two patients with fatal reducing body myopathy showed few necrotic or regenerating fibers. On the other hand, enlarged densely stained myonuclei, in addition to the presence of many reducing bodies, were striking on light microscopy, and chromatin condensation was seen on electron microscopy. To confirm the involvement of apoptosis, we performed the TUNEL method at the electron microscopic level on muscles of the two patients and five age-matched controls. The density of DNA fragments in myonuclei showing chromatin condensation was significantly higher in reducing body myopathy compared to that in control muscles. In addition, the myonuclei surrounded by many reducing bodies tended to show more intense chromatin condensation and a higher density of DNA fragments than those distant from the reducing bodies. These results suggest that apoptosis takes part in muscle fiber degeneration in fatal reducing body myopathy, although the precise relationship between reducing bodies and apoptosis is uncertain.


Lay person use of automatic external defibrillation.
The ability of lay persons to learn and retain defibrillation skills using an automatic external defibrillator (AED) was assessed. Thirty-four family members of cardiac arrest survivors were trained in CPR techniques and defibrillation, and evaluated for performance of skills immediately following training and at six-week and three-month follow-ups. All but two were successfully trained to complete three cycles of CPR interspersed with three defibrillatory shocks in an average of four minutes with the first shock delivered in an average of two minutes. Although there were decrements in the speed and quality of performance at each follow-up period (P less than .01), we conclude that most lay persons can learn to operate an AED safely and under simulated conditions provide defibrillatory shocks an average of eight minutes faster than typical response times of emergency medical technicians. These results suggest that AEDs can be placed in many homes of patients at high risk for cardiac arrest.


A Comparison of EIS and QCM NanoMIP-Based Sensors for Morphine.
In this work we have compared two different sensing platforms for the detection of morphine as an example of a low molecular weight target analyte. For this, molecularly imprinted polymer nanoparticles (NanoMIP), synthesized with an affinity towards morphine, were attached to an electrochemical impedance spectroscopy (EIS) and a quartz crystal microbalance (QCM) sensor. Assay design, sensors fabrication, analyte sensitivity and specificity were performed using similar methods. The results showed that the EIS sensor achieved a limit of detection (LOD) of 0.11 ng·mL-1, which is three orders of magnitude lower than the 0.19 µg·mL-1 achieved using the QCM sensor. Both the EIS and the QCM sensors were found to be able to specifically detect morphine in a direct assay format. However, the QCM method required conjugation of gold nanoparticles (AuNPs) to the small analyte (morphine) to amplify the signal and achieve a LOD in the µg·mL-1 range. Conversely, the EIS sensor method was labor-intensive and required extensive data handling and processing, resulting in longer analysis times (~30-40 min). In addition, whereas the QCM enables visualization of the binding events between the target molecule and the sensor in real-time, the EIS method does not allow such a feature and measurements are taken post-binding. The work also highlighted the advantages of using QCM as an automated, rapid and multiplex sensor compared to the much simpler EIS platform used in this work, though, the QCM method will require sample preparation, especially when a sensitive (ng·mL-1) detection of a small analyte is needed.


Large basilar aneurysm with posterior inferior cerebellar artery stroke and consequential fatal subarachnoid hemorrhage.
Basilar artery aneurysm presenting a stroke is rare, and we present a case of this along with a discussion of the management options available.


Physicochemical considerations in the formulation development of silicone elastomer vaginal rings releasing 5-nitroimidazole drugs for the treatment of bacterial vaginosis.
Bacterial vaginosis (BV) is a common dysbiosis of the human vaginal microbiota characterized by depletion of hydrogen peroxide and lactic acid-producing Lactobacillus bacteria and an overgrowth of certain facultative anaerobic bacteria. Although short-term cure rates following treatment with frontline antibiotics (most notably oral metronidazole (MNZ), clindamycin vaginal cream, and MNZ vaginal gel) are generally high, longer-term recurrence rates are an issue. The development of vaginal formulations offering continuous/sustained administration of antibiotic drugs over one or more weeks might prove useful in reducing recurrence. Here, we report the manufacture and preclinical testing of matrix-type vaginal rings offering sustained release of four 5-nitroimidazole antimicrobial drugs either being used clinically or having potential in treatment of BV - MNZ, tinidazole (TNZ), secnidazole (SNZ) and ornidazole (ONZ). All four drugs showed good compatibility with a medical-grade addition-cure silicone elastomer based upon thermal analysis experiments, and matrix-type rings containing 250 mg (3.125 %w/w) of each drug were successfully manufactured by reaction injection molding. 28-day in vitro drug release studies demonstrated root-time kinetics, with daily release rates of 25, 22, 9 and 6 mg/day½ for SNZ, ONZ, MNZ and TNZ, respectively. The rank order of drug release from rings correlated with the simple molecular permeability parameter S/V, where S is the measured drug solubility in silicone fluid and V is the drug molecular volume. The relative merits of SNZ and ONZ over MNZ (the current reference treatment) are discussed. The data support development of vaginal rings for sustained release of 5-nitroimidazole compounds for treatment of BV.


Advances in corneal stem-cell transplantation in rabbits with severe ocular alkali burns.
To evaluate the efficacy of autologous corneal epithelial sheet implantation in restoring transparency of rabbit corneas severely injured by alkaline and the effect of photocoagulation in arresting corneal neovessel ingrowth. Ophthalmology Department, School of Biomedical Sciences, Universidad Austral, Buenos Aires, Argentina. Limbal stem-cell deficiency (LSCD) was induced in 14 rabbits by alkali burns. A limbal cell biopsy was done in the contralateral eye, and the cells were cultured on a fibroblast feeder layer grown on autologous clotted platelet-poor plasma or commercial fibrin for 21 days. Anterior keratectomy was followed by suturing corneal cell sheets over the stroma. If regrowth of vessels occurred, argon laser photocoagulation was applied to them. Rabbits were killed at 30, 60, 90, 180, and 360 days and the corneas processed for histopathology and inmunohistochemistry. A small (2.5 mm(2)) limbal biopsy achieved stem-cell replication in vitro. Corneal clarity and epithelial defects evolved with a trend toward improvement. There was a significant reduction in corneal neovascularization. Histology showed a multilayered stratified epithelium including several epithelial-like cells with clear cytoplasm in the deepest part. There were no signs of intraepithelial mucin cells on the implanted corneas. Immunohistochemical results showed expression of cytokeratins 3 and 12 in the central corneal epithelium and an absence of cytokeratin 19. Autologous limbal epithelial cell transplantation improved the corneal surface in eyes with LSCD. Photocoagulation of neovessel ingrowth was effective over the 1-year follow-up. Results may facilitate the application of this technique in patients.


Rare NF1 Gene Mutation in Chinese Patient with Neurofibromatosis Type 1 and Anaplastic Astrocytoma.
Neurofibromatosis type 1 (NF1), a dysregulated neurocutaneous disorder, is an autosomal dominant genetic disease caused by mutations in the NF1 gene. Anaplastic astrocytoma is rare in NF1 patients, and research has proposed that high-grade astrocytomas could be due to larger germ-line mutations in NF1.We present a clinical and molecular study of a Chinese family with NF1. A 28-year-old male patient with NF1 presents with headache, vertigo, and dizziness. Histopathologic examination and molecular features identified a cerebellar anaplastic astrocytoma, IDH-wildtype. The patient underwent gross total resection of the lesion and received radiotherapy and chemotherapy. A rare splice error mutation (c.4110+945A>G) in intron 23-2 of NF1 was identified by next-generation sequencing in the proband. Sanger sequencing identified and confirmed it in some affected family members. We present a unique case of NF1 with anaplastic astrocytoma that revealed a rare splice error mutation in the NF1 gene in the family.


Compartment syndrome in all four extremities: a rare case associated with systemic capillary leak syndrome.
While isolated limb injuries often lead to suspicion for and treatment of compartment syndrome, multi-limb compartment syndrome induced by a systemic disease is a rare entity, in which lack of immediate diagnosis can have catastrophic consequences to the patient. We present a patient with idiopathic systemic capillary leak syndrome (SCLS) resulting in compartment syndrome in all four extremities. Treatment required bilateral hand, forearm, calf, and thigh fasciotomies. Presenting symptoms included pain in all four extremities, malaise, and confusion. Laboratory data included polycythemia, hypoalbuminemia, leukocytosis, and elevated creatinine, but not a monoclonal spike on serum electrophoresis as is common in SCLS. Thus, when faced with clinical evidence of multiple extremity compartment syndrome, the surgeon should consider systemic disorders, such as SCLS, and aggressively treat the compartment syndrome as well as the underlying disease.


Terahertz spectral properties of glucose and two disaccharides in solid and liquid states.
The vibrational and rotational frequencies of most biological macromolecules fall within the terahertz (THz) band; therefore, the THz wave has a strong ability to distinguish substances. Saccharides are important organic substances and the main source of life-sustaining activities. In this study, the spectral characteristics of D-glucose, α-lactose hydrate, and β-maltose hydrate were measured in the solid state through THz time-domain spectroscopy in the frequency range of 0.1-2.5 THz. The crystal configurations of these three saccharides were then simulated using solid-state density functional theory, and the experimental results were found to be in good agreement with the simulation results. Furthermore, the spectral characteristics of the three saccharides in solutions were measured. Each saccharide was found to have unique spectral characteristics, and a correlation existed between the THz absorption spectra of the same substance in the solid state and aqueous solution.


Risk factors and outcome of failure to progress during the first stage of labor: a population-based study.
One of the major indications for Cesarean section (CS) is failure of labor to progress. This study was aimed at defining obstetric risk factors for failure of labor to progress during the first stage, and to determine pregnancy outcome. A population-based study comparing all singleton, vertex, term deliveries between the years 1988 and 1999 with an unscarred uterus, complicated with failure of labor to progress during the first stage with deliveries without non-progressive labor (NPL). Multiple logistic regression analysis was performed to investigate independent obstetric risk factors associated with failure of labor to progress during the first stage. Failure to progress during the first stage of labor complicated 1.3% (n = 1197) of all deliveries included in the study (n = 92 918), and resulted in CS. Independent risk factors for failure of labor to progress during the first stage, using a multivariable analysis, were premature rupture of membranes (PROM; OR = 3.8, 95% CI 3.2-4.5), nulliparity (OR = 3.8, 95% CI 3.3-4.3), labor induction (OR = 3.3, 95% CI 2.9-3.7), maternal age > 35 years (OR = 3.0, 95% CI 2.6-3.6), birth weight > 4 kg (OR = 2.2, 95% CI 1.8-2.7), hypertensive disorders (OR = 2.1, 95% CI 1.8-2.6), hydramnios (OR = 1.9, 95% CI 1.5-2.3), fertility treatment (OR = 1.8, 95% CI 1.4-2.4), epidural analgesia (OR = 1.6, 95% CI 1.4-1.8) and gestational diabetes (OR = 1.4, 95% CI 1.1-1.7). Although newborns delivered after failure of labor to progress during the first stage had significantly higher rates of Apgar scores lower than 7 at 1 and 5 min as compared with the controls (18.2% vs. 2.1%; P < 0.001 and 1.3% vs. 0.2%; P < 0.001, respectively), no significant differences were noted between the groups regarding perinatal mortality (0.3% vs. 0.4%; P = O.329). Maternal anemia and accordingly packed cells transfusion (47.4% vs. 22.8%; P < 0.001 and 5.6% vs. 1.0%; P < 0.001, respectively) were higher among pregnancies complicated with failure of labor to progress during the first stage as compared with the controls. Major risk factors for failure of labor to progress during the first stage were PROM, nulliparity, induction of labor and older maternal age. Indications for labor induction should be carefully evaluated in order to decrease the rate of operative deliveries.


Effect of nitrous oxide inactivation of vitamin B12-dependent methionine synthetase on the subcellular distribution of folate coenzymes in rat liver.
The effects of nitrous oxide inactivation of the vitamin B12-dependent enzyme, methionine synthetase (EC 220.127.116.11), on the subcellular distribution of hepatic folate coenzymes was determined. In controls, cytosolic folates were 5-methyltetrahydrofolate (45%), 5- and 10-formyltetrahydrofolate (9 and 19%, respectively), and tetrahydrofolate (27%). Exposure of rats to an atmosphere containing 80% nitrous oxide for 18 h resulted in a marked shift in this distribution pattern to 5-methyltetrahydrofolate, 84%; 5- and 10-formyltetrahydrofolate, 2.1 and 9.1%, respectively; and tetrahydrofolate, 4.7%. Activity of the cytosolic enzyme, methionine synthetase, was reduced by about 84% as compared to that of air breathing controls. In controls, mitochondrial folates were 5-methyltetrahydrofolate (7.3%), 5- and 10-formyltetrahydrofolate (11.5 and 33.1%, respectively), and tetrahydrofolate (48.1%). This distribution did not change after exposure to nitrous oxide. These results show that the effects of nitrous oxide inactivation of vitamin B12 are confined to the cytosol, at least in the short term, and suggest that there is little, if any, transport of free folates between the cytosolic and mitochondrial compartments.


Metal-Free Addition of Benzyl Halides to Aldehydes Using Super Electron Donors: Access to 3,4-Dihydroisocoumarins and 1,2-Diarylethanols.
We report here the intermolecular metal-free addition reaction of functionalized benzyl halides to aldehydes using a super electron donor (SED). The metal-free and mild conditions allowed the formation of 3,4-dihydroisocoumarins and 1,2-diarylethanols with unprecedented functional group tolerance.


Analysis of trace atrazine and simazine in environmental samples by liquid chromatography-fluorescence detection with pre-column derivatization reaction.
Coupled with off-line extraction, a pre-column derivatization liquid chromatographic fluorescence detection (LC-FL) procedure was developed for the determination of atrazine and simazine in soil, crop and water samples. Concentrations in real samples were expected to be at or below the low ng/g level, which requires pre-concentration of analytes and improved detection. 4-(2-Phthalimidyl) benzoyl chloride (PIB-Cl) was used as a pre-column derivation reagent for high-performance liquid chromatography. The clean-up and second-time concentration procedures, which were indispensable in the conventional analytical methods for soil and crop analysis because of the complexity of the samples, were replaced by a derivatization reaction between PIB-Cl and the analytes. The fluorescent and ultraviolet characteristics of the derivatives were investigated. The derivatization reaction and chromatographic separation conditions were optimized systematically. Detection limits of 1.2 ng/g for atrazine and 1.1 ng/g for simazine were obtained with recoveries of 84-95% for environmental samples. On the basis of practical application to five soil and five crop samples, the LC-FL method was compared with the conventional GC-MS method.


Operational Characteristics of Linear Concentration-QT Models for Assessing QTc Interval in the Thorough QT and Phase I Clinical Studies.
Concentration-QTc (C-QTc) analysis can be used as an alternative to the standard statistical methods in clinical QT studies. Pharmacokinetic/pharmacodynamics (PK/PD) simulations were performed to assess the operating characteristics of four C-QTc models. False negatives were 2-6% for crossover and 2-9% for parallel studies, with 12 to 60 subjects per treatment for a dose with 10-ms mean effect. All C-QTc models tested gave less than +1 ms mean bias in the ΔΔQTcmax prediction. The power to exclude 10 ms was >80% across all study designs and sizes, for a dose with 3-ms mean effect. The study demonstrates that linear C-QTc models have adequate sensitivity and specificity when the simulation and data analytical models are the same. C-QTc models that incorporate time- and treatment-specific terms give the least biased ΔΔQTcmax predictions under scenarios of model-misspecifications and offer an advantage when applying to real clinical data where the underlying relationship is not known.


Role of vitamin D treatment in glucose metabolism in polycystic ovary syndrome.
To determine the effect of treatment with vitamin D(3) analogue in the parameters of glucose metabolism in obese women with polycystic ovary syndrome (PCOS). Observational study. Obese women with PCOS in an academic research environment. Fifteen obese women (mean age 28 +/- 1.3 years, mean body mass index 32.55 +/- 0.43) with documented chronic anovulation and hyperandrogenism were recruited into the study. Alphacalcidol (1-alpha-hydroxyvitamin D(3)) was administered orally 1 microg/day for 3 months. All subjects underwent a frequently sampled IV glucose tolerance test after a 10- to 12-hour overnight fast during a spontaneous bleeding episode before and after treatment with alphacalcidol. Peripheral insulin resistance and insulin effectiveness were estimated with minimal model. The first phase of insulin secretion was significantly increased after treatment with alphacalcidol. A favorable statistically significant change also was observed in the lipid profile. Treatment with the vitamin D(3) analogue (alphacalcidol) could be of value in the management of PCOS.


Electrophysiological analysis of visual function in mutant mice.
The mouse has become a key animal model for ocular research. This situation reflects the fact that genes implicated in human retinal disorders or in mammalian retinal function may be readily manipulated in the mouse. Visual electrophysiology provides a means to examine retinal function in mutant mice, and stimulation and recording protocols have been developed that allow the activity of many classes of retinal neurons to be examined and which take into account unique features of the mouse retina. Here, we review the mouse visual electrophysiology literature, covering techniques used to record the mouse electroretinogram and visual evoked potential, and how these have been applied to characterize the functional implications of gene mutation or manipulation in the mouse retina.


The association between anatomic site and survival in malignant melanoma. An analysis of 12,353 cases from the Swedish Cancer Registry.
The relationship between site and survival in cutaneous malignant melanoma was investigated by a follow-up of 12,353 Swedish patients diagnosed in 1960-1982. In males, the poorest prognosis was found for tumors located on the scalp-neck region (5-year relative survival rate, RS51%), followed by the lower extremity (RS66%) and trunk (RS68%). Among females, the poorest prognosis was noted for tumors located on the external ear (5-year RS 71%), trunk (RS 78%) and scalp-neck (RS 78%). The prognosis varied considerably between the sites of the head-neck region--for eyelid and facial lesions the prognosis was good, but for external ear and scalp-neck tumors it was poor. Multivariate analysis taking into account age and year of diagnosis showed the highest relative hazards (RH) for female lesions of the trunk (1.40) and male scalp-neck tumors (1.65), with the upper extremity used as reference (RH = 1.00). Except for lesions of the trunk, no significant differences in RH were found between the various sites after 4 years of observation.


Risk of hip fracture among older people using antihypertensive drugs: a nationwide cohort study.
Many people with a high risk of hip fracture have coexisting cardiovascular diseases. We aimed to examine associations between exposure to antihypertensive drugs and the risk of hip fracture among older people. We conducted a cohort study of the 906,422 people born before 1945 and living in Norway in 2005. We obtained information on all prescriptions of antihypertensive drugs dispensed (the Norwegian Prescription Database) in 2004-2010 and the dates of primary hip fractures (the Norwegian Hip Fracture Registry) in 2005-2010. We compared the incidence rates of hip fracture during the time people were exposed and unexposed to antihypertensive drugs by calculating the standardized incidence ratio (SIR). Altogether, 39,938 people experienced a primary hip fracture (4.4 %). The risk of hip fracture was decreased among people exposed to thiazides (SIR 0.7, 95 % confidence interval (CI) 0.6-0.7), beta-blockers (SIR 0.7, 95 % CI 0.7-0.8), calcium channel blockers (SIR 0.8, 95 % CI 0.8-0.8), angiotensin II receptor blockers (SIR 0.8, 95 % CI 0.7-0.8), ACE inhibitor/thiazide combination products (SIR 0.7, 95 % CI 0.6-0.7) and angiotensin II receptor blocker/thiazide combination products (SIR 0.6, 95 % CI 0.6-0.6). Use of loop diuretics and ACE inhibitors (plain products) was associated with increased fracture risk in people born after 1924, and with decreased risk in those born before 1925. The protective associations were stronger among exposed men than among exposed women for all drugs except loop diuretics. The SIRs decreased with increasing age among exposed people, except for thiazides and angiotensin II receptor blockers. We found a reduced risk of hip fracture associated with overall use of most antihypertensive drugs, but an increased risk with loop diuretics and ACE inhibitors among people younger than 80 years and in new users of loop diuretics. This may have great impact at the population level, because the use of antihypertensive drugs is widespread in people at risk of hip fracture. Clinical studies are needed to further explore these associations.


Medical education in Southeast Asia: emerging issues, challenges and opportunities.
Medical education in Southeast Asian countries is undergoing rapid changes, with the realignment of medical schools' curricula to meet national needs and priorities, the adoption of and experimentation with innovations, and greater emphasis on staff development initiatives. The Medical Education Unit of the National University of Singapore undertook a project to compile the educational processes taking place in these medical schools. This was a process-focused initiative. We developed a custom-made questionnaire that emphasised narrative description. We compiled profiles of 30 selected medical schools in the Southeast Asian region and, after editing and review, published these profiles. This report summarises the key findings from the project. Medical schools in Southeast Asia are in a dynamic state. Schools are gradually adopting student-centred learning approaches, including problem-based learning. Many schools offer their students early clinical training, opportunities for out-of-hospital postings, and student-selected electives. Multiple-choice questions and oral examinations are almost universally used in student assessment. Portfolios and self- and peer-assessments are seldom used. Major challenges faced by the schools involve shortages of qualified staff and financial constraints. Major goals for the future include the implementation of student-centred learning, the revamping of the assessment process, and staff training. This is a compilation of self-reported profiles of selected medical schools where we encouraged self-reflection and analysis. As with other surveys, there could be potential self-selection bias. Nevertheless, the profiles of these selected schools provide a broad overview of the status of medical schools in Southeast Asia.


FAK and PYK2 interact with SAP90/PSD-95-Associated Protein-3.
Focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2) are two related non-receptor tyrosine kinases highly expressed in brain. Although they are both involved in synaptic plasticity, little is known about their specific neuronal partners. Using a yeast two-hybrid screen and GST pull-down assays we show that SAPAP3 (SAP90/PSD-95-Associated Protein-3) interacts with FAK (residues 676-840) and PYK2. The three proteins partly co-distribute in the same sucrose gradient fractions as the post-synaptic density protein PSD-95 and Src. Our results suggest that SAPAP3 is an anchoring protein for FAK and PYK2 in post-synaptic densities and may contribute to the synaptic function of these tyrosine kinases.


Central auditory processing. III. The "cocktail party" effect and anterior temporal lobectomy.
The capacity to selectively attend to only one of multiple, spatially separated. simultaneous sound sources--the "cocktail party" effect--was evaluated in normal subjects and in those with anterior temporal lobectomy using common environmental sounds. A significant deficit in this capacity was observed for those stimuli located on the side of space contralateral to the lobectomy, a finding consistent with the hypothesis that within each anterior temporal lobe is a mechanism that is normally capable of enhancing the perceptual salience of one acoustic stimulus on the opposite side of space, when other sound sources are present on that side. Damage to this mechanism also appears to be associated with a deficit of spatial localization for sounds contralateral to the lesion.


Rhino-orbital-cerebral mucormycosis and aspergillosis: differential diagnosis and treatment.
In immunocompromised patients, symptoms and the pathogen spectrum of sinusitis are frequently atypical. If progressive loss of vision occurs, an infection of the anterior skull base or nasal sinuses should be considered. We report on four patients with orbit-associated symptoms. CT-imaging revealed bony defects in sinus borders to orbits or endocranium. In all the cases immediate surgical drainage was performed because complications following sinusitis were suspected. Histopathological diagnosis revealed two cases of aspergillosis and mucormycosis. The possibility of opportunistic infections by saprophytic fungi must be taken into account in immunocompromised patients, as they may endanger both vision and survival. Immediate diagnosis and therapy are essential. Nowadays, therapeutic success can be achieved due to advances in antimicrobial therapy, hyperbaric oxygen therapy and treatment of the underlying disease. Radical procedures like orbital exenteration must be considered in all cases. The current state of diagnostics, therapy and prognosis is discussed based on these case reports and the recent literature.


Directed stimulation with interfascicular interfaces for peripheral nerve stimulation.
Objective.Computational models have shown that directional electrical contacts placed within the epineurium, between the fascicles, and not penetrating the perineurium, can achieve selectivity levels similar to point source contacts placed within the fascicle. The objective of this study is to test, in a murine model, the hypothesis that directed interfascicular contacts are selective.Approach.Multiple interfascicular electrodes with directional contacts, exposed on a single face, were implanted in the sciatic nerves of 32 rabbits. Fine-wire intramuscular wire electrodes were implanted to measure electromyographic (EMG) activity from medial and lateral gastrocnemius, soleus, and tibialis anterior muscles.Main results.The recruitment data demonstrated that directed interfascicular interfaces, which do not penetrate the perineurium, selectively activate different axon populations.Significance.Interfascicular interfaces that are inside the nerve, but do not penetrate the perineurium are an alternative to intrafascicular interfaces and may offer additional selectivity compared to extraneural approaches.


Two octanordammarane triterpenes from Commiphora kua.
The resin of Commiphora kwo yielded two new octanordammarane triterpenes namely 15 alpha-hydroxymansumbinone and 28-acetoxy-15 alpha-hydroxymansumbinone, along with the four known compounds, mansumbinone, mansumbinol, (16S, 20R)-dihydroxydammar-24-en-3-one and T-cadinol. These structures were elucidated by spectroscopic techniques, including 1D and 2D NMR spectroscopy, and X-ray analysis.


First record of the avian ectoparasite Philornis downsi Dodge & Aitken, 1968 (Diptera: Muscidae) in Argentina.
Species of Philornis Meinert, 1890 (Diptera, Muscidae) are Neotropical dipterans that include species with parasitic larvae which feed on nestling birds. To date, all Philornis species that have been recorded from Argentina have parasitic subcutaneous larvae. Here, for the first time for Argentina, we report the finding of Philornis downsi Dodge & Aitken, 1968, a fly with a nest-dwelling, semi-haematophagous larva. This record, from the humid Chaco ecoregion of Argentina in the nest of a saffron finch Sicalis flaveola pelzelni Sclater, substantially extends the known distribution of this species. We also report the consensus sequences of the internal transcribed spacer 1 (ITS1) and ITS2 regions of three of the specimens for future reference and comparison. Further investigation is needed to determine whether Argentina is part of the historical range of P. downsi or, alternatively, represents a recent expansion of its range, perhaps due to climatic changes or other factors of global environmental variation.


Profiling hymenopteran venom toxins: Protein families, structural landscape, biological activities, and pharmacological benefits.
Hymenopterans are an untapped source of venom secretions. Their recent proteo-transcriptomic studies have revealed an extraordinary pool of toxins that participate in various biological processes, including pain, paralysis, allergic reactions, and antimicrobial activities. Comprehensive and clade-specific campaigns to collect hymenopteran venoms are therefore needed. We consider that data-driven bioprospecting may help prioritise sampling and alleviate associated costs. This work established the current protein landscape from hymenopteran venoms to evaluate possible sample bias by studying their origins, sequence diversity, known structures, and biological functions. We collected all 282 reported hymenopteran toxins (peptides and proteins) from the UniProt database that we clustered into 21 protein families from the three studied clades - wasps, bees, and ants. We identified 119 biological targets of hymenopteran toxins ranging from pathogen membranes to eukaryotic proteases, ion channels and protein receptors. Our systematic study further extended to hymenopteran toxins' therapeutic and biotechnological values, where we revealed promising applications in crop pests, human infections, autoimmune diseases, and neurodegenerative disorders.


Clinical experience with implantable scanning tachycardia reversion pacemakers.
An automatic, fully implantable scanning pacemaker was developed and has been used for tachycardia termination in man. Since January 1982, 22 patients have had this pacemaker implanted at St. Bartholomew's Hospital and over 125 devices have been used throughout the world. Clinical results have been encouraging, especially with the second-generation device.


Thalamic altered spontaneous activity and connectivity in obstructive sleep apnea syndrome.
Obstructive sleep apnea (OSA) syndrome is a sleep disorder characterized by excessive snoring, repetitive apneas, and nocturnal arousals, that leads to fragmented sleep and intermittent nocturnal hypoxemia. Morphometric and functional brain alterations in cortical and subcortical structures have been documented in these patients via magnetic resonance imaging (MRI), even if correlational data between the alterations in the brain and cognitive and clinical indexes are still not reported. We examined the impact of OSA on brain spontaneous activity by measuring the fractional amplitude of low-frequency fluctuations (fALFF) in resting-state functional MRI data of 20 drug-naïve patients with OSA syndrome and 20 healthy controls matched for age, gender, and body mass index. Patients showed a pattern of significantly abnormal subcortical functional activity as compared to controls, with increased activity selectively involving the thalami, specifically their intrinsic nuclei connected to somatosensory and motor-premotor cortical regions. Using these nuclei as seed regions, the subsequent functional connectivity analysis highlighted an increase in patients' thalamocortical connectivity at rest. Additionally, the correlation between fALFF and polysomnographic data revealed a possible link between OSA severity and fALFF of regions belonging to the central autonomic network. Our results suggest a hyperactivation in thalamic diurnal activity in patients with OSA syndrome, which we interpret as a possible consequence of increased thalamocortical circuitry activation during nighttime due to repeated arousals.


Variability of Norway spruce (Picea abies L.) needles; performance of spruce sawflies (Gilpinia hercyniae Htg.).
Larvae of the spruce sawfly Gilpinia hercyniae were reared on whole branches of Norway spruce, Picea abies. Top and low branches were selected from flowering and nonflowring stands. Sawfly performance from the larval L2-stage until the fertile egg stage of the next generation was recorded. Growth and development were best on top branches from the flowering stand, poorest on branches from windblown, partly derooted and heavily flowering trees. Analysis of some 30 biochemicals in needles and faeces was performed. New needles had the highest concentrations of some nutrients (total nitrogen, amino acids), however, G. hercyniae larvae only fed on old needles, a 100% mortality being recorded on newly flushed needles, probably because these needles also contained the highest concentrations of the secondary compound, quinic acid. Old needles showed high variability in concentrations of nutrients and secondary compounds. Regression analysis demonstrated that the total amount of carbohydrates (glucose, fructose and sucrose) was significantly correlated with the larval linear growth rate, the maximal larval weight, the cocoon weight and the number of eggs per female. In these performance variables 72-88% of the variation could be explained by five biochemicals. Survival rates of larvae or pupae and the instantaneous growth rate could not be explained by the biochemical variables. Only weak correlations were found between nitrogen or amino acids and performance variables. Assimilation of the various biochemicals was calculated and showed high rates (90-97%) in hexoses and lower rates (38-65%) in total nitrogen and amino acids.


Cryptopsychobiology: the appearance, disappearance, and reappearance of a species-typical action pattern during early development.
Late in gestation, intraoral infusion of lemon elicits a facial wiping response from rat fetuses. This facial wiping response is isomorphic with that of older pups and adult rats exposed to aversive oral stimulation. Most studies of the postnatal development of aversive responses have demonstrated that facial wiping does not appear in the repertoire of rat pups until the second postnatal week. In certain test situations, however, wiping can be elicited from neonatal rats. This fact suggests that the expression of facial wiping by neonates is constrained or facilitated by the environmental conditions present at the time of testing. In this report, a series of seven experiments is described that document the wiping response of rat fetuses and pups in age-typical environments, and an environmental constraint hypothesis is examined. Examination of the ontogeny of facial wiping in this manner highlights issues that should be addressed in studies of behavioral continuity between the prenatal and the postnatal periods.


Survival of selected pathogens in diluted sludge of a thermophilic waste treatment plant and in NaCl-solution under aerobic and anaerobic conditions.
Decimal reduction times (DRT or D-value) of Campylobacter jejuni, Salmonella enterica (formerly Salmonella choleraesuis) serovar Senftenberg, Escherichia coli, and Listeria monocytogenes were determined in two different matrices, diluted fermenter sludge (DFS) and 0.95% NaCl-solution (NaCl) at 50 degrees C, both under aerobic and anaerobic conditions. Depending on aeration, matrix composition, and the respective organism, the D-values varied between 10min and more than 15h. Generally the viability of bacteria decreased faster in DFS compared to NaCl-solution and under aerobic compared to anaerobic conditions. After 24h no viable cells could be detected in DFS, both under aerobic as well as under anaerobic conditions, whereas viable cells were still found in NaCl solutions. In both matrices the detection limits determined by means of PCR-based and classical microbiological methods were compared and pointed to lower detection limits of the latter methods. Results of the present investigation show that test organisms were far from surviving several days in DFS whereas hydraulic retention times normally used for thermophilic anaerobic digestion are in the range of 2 weeks. However, an underestimation of survival rates of the test organisms seems probable when applying aerobic standard methods.


Ligaments and articular contact guide passive knee flexion.
The aim of this study was to test the hypothesis that the coupled features of passive knee flexion are guided by articular contact and by the isometric fascicles of the ACL, PCL and MCL. A three-dimensional mathematical model of the knee was developed, in which the articular surfaces in the lateral and medial compartments and the isometric fascicles in the ACL, PCL and MCL were represented as five constraints in a one degree-of-freedom parallel spatial mechanism. Mechanism analysis techniques were used to predict the path of motion of the tibia relative to the femur. Using a set of anatomical parameters obtained from a cadaver specimen, the model predicts coupled internal rotation and ab/adduction with flexion. These predictions correspond well to measurements of the cadaver specimen's motion. The model also predicts posterior translation of contact on the tibia with flexion. Although this is a well-known feature of passive knee flexion, the model predicts more translation than has been reported from experiments in the literature. Modelling of uncertainty in the anatomical parameters demonstrated that the discrepancy between theoretical predictions and experimental measurement can be attributed to parameter sensitivity of the model. This study shows that the ligaments and articular surfaces work together to guide passive knee motion. A principal implication of the work is that both articular surface geometry and ligament geometry must be preserved or replicated by surgical reconstruction and replacement procedures to ensure normal knee kinematics and by extension, mechanics.


Different susceptibilities to cyclosporin A of the mitogenic and potentiating activities of interleukins.
A dissociation was observed between the mitogenic and potentiating activities of interleukins (ILs)-1 or -2 in murine thymocyte cultures treated with drugs. The direct mitogenic effects of the ILs were unaffected by cyclosporin A (CsA) at concentrations which abolished the potentiating activities of these mediators, i.e. their synergy with lectins. Conversely to CsA, dexamethasone was more inhibitory to the mitogenic activity of the ILs than to their synergistic reactions with the lectins. The resistance to CsA of the mitogenic activity of IL-1 was unexpected since this response is assumed to be mediated by newly formed IL-2 and CsA inhibits IL-2 production. This resistance was further tested by coculturing thymocytes with the IL-2-dependent CT6 cells; net gains of thymidine uptake by the cocultures were attributed to IL-2 release. Such net gains were observed in cocultures stimulated with IL-1 alone and were relatively resistant to CsA. On the other hand, net gains stimulated by mitogenic lectins, alone or with IL-1, were eliminated by CsA. These results support the notion that IL-1 direct activity on thymocytes is mediated by newly released IL-2 and show that this IL-1 activity is unusual in being resistant to CsA. Low levels of protection against CsA were also observed in cultures potentiated by IL-1: lymphocytes stimulated by lectins or antigens and IL-1 were inhibited by CsA less than lymphocytes stimulated without IL-1. Yet, this partial protection by IL-1 was achieved only at CsA concentrations about 100 fold lower than those resisted by thymocytes directly stimulated by IL-1.


[A case of recurrent esophageal cavernous hemangioma increasing rapidly after surgery].
A 40-year-old female was referred to our hospital for dysphagia. A hemangioma measuring 5 x 2.5 x 2.5 cm was revealed as a round defect by esophagography and was partially cystic on CT and MRI. Through a neck incision, the esophageal wall on the tumor side was initially opened. The tumor partially adhered to the esophageal wall, but was dissected from the esophageal wall and then resected easily. Microscopic examination of tumor revealed cavernous hemagioma. Thirty days after the initial surgery, the recurrent tumor was detected in the pharynx and increased rapidly. Then a second operation was performed. The tumor was completely resected by mucosectomy including normal esophageal mucosa. Recurrence was caused by residual cystic wall of the hemangioma adhering to the esophageal mucosa after the first procedure.


[cardiovascular system and cognitive disorders in male drivers].
The authors found statistically significant differences in cognitive tests results between group of drivers and reference group (p = 0,021). Correlation analysis proves statistically reliable relationship between cognitive functions and hemodynamic as well as morphologic parameters of cardiovascular system.


The evolutionary history of PDR in Brachypodium distachyon polyploids.
The ATP-binding cassette transporter genes include the pleiotropic drug resistance (PDR) family found only in fungi and plants. These transporters transport toxic compounds across biological membranes. Here, we investigated the evolution of the PDR1 gene in Brachypodium distachyon, a widely distributed temperate grass species that belongs to the Poaceae (Gramineae) family, which also contains the domesticated cereal crops. Because this species has multiple ploidy levels, investigating PDR1 evolution in B. distachyon will offer insights into the formation and evolution of polyploidy. From 23 B. distachyon ecotypes, 39 PDR1 homologs were identified. All ecotypes had either one or two PDR1 copies. Based on restriction site analysis, the PDR1 homologs were classified as E or H type. All but one diploid and tetraploid ecotypes had only a single H type PDR1. All but one hexaploid ecotypes had both an E and a H type PDR1. Phylogenetic analysis revealed that each type formed a well-supported cluster. The two PDR1 types appeared to evolve differently. These different evolutionary patterns could indicate a difference in age between the two types or might indicate different mutation rates or selection pressures on the two types. The phylogenetic analysis also revealed that the hexaploid ecotypes shared a genomic origin for their E type PDR1, but there were multiple origins for hexaploid H type PDR1 homologs. Overall, the results suggest that tetraploid and hexaploid might be misnomers in B. distachyon and suggest a complex polyploidization history during B. distachyon evolution.


Trends in black fly density, parity and infection rates from riverside to villages of the Bafia Health District in Cameroon: implication for onchocerciasis vector control.
Reducing contact between humans and black flies can lead to interruption of onchocerciasis transmission. The Esperanza Window Trap (EWT) has been shown to be an effective tool for reducing black fly densities. Several shape-based improvements to this trapping system have been made to optimise its effectiveness, but optimisation of this trapping system has been based most often on the shape of the trap, collection in areas of high black fly density and the addition of attractants, without considering transmission potentials and parity rates. This study aims to investigate the differences in biting rates and transmission potential between three catch points along a transect to guide the choice of EWT placement. Monthly black fly collection was carried out over a 1-year study period using the human landing method at three catch points along a transect from the riverside toward the centre of two first-line villages (Biatsota and Bayomen), in the Mbam valley in Cameroon. All female black flies caught were counted and dissected, and entomological indicators were computed and compared between the catch points and villages. A total of 80,732 black flies were caught, of which 57,517 were dissected; of the latter, 2743 (4.8%) were parous and 44 (1.6%) were infective. Regarding the distance to the river, a vector density gradient was observed, with the highest annual biting rates being recorded at the riverside. The highest annual transmission potentials were also recorded at the riverside (165 vs 255 infective larvae/man/year in Bayomen and Biatsota, respectively). Overall, the highest parity rates were recorded at the riverside in Biatsota (5.1%) where various human activities are frequent and at the centre of Bayomen village (6.3%). The results of this study reveal that entomological parameters were the highest at the riverside catch sites and indicate that riverside locations should be prioritised for EWTs or other trapping systems to achieve optimal performance in onchocerciasis control.


Rare Association of Ankyloblepharon Filiforme Adnatum (AFA) with Cleft Palate - Case Report.
The aim of this article is to discuss about rare representation of ankyloblepharon (an established chromosomal anomaly with aberration of p53 inherited as an autosomal dominant trait) with cleft of palate without any other feature of ectodermal dysplasia. The need to surgically address ankyloblepharon in order to avoid complications is also discussed.


[Holism at the heart of nursing knowledge: a proposed model for teaching it in nursing].
The concept of holism remains difficult to grasp and to teach because of its polysemous nature. In the current reflections on the construction of nursing curricula, it seems necessary to propose some reference points in the meaning given to this widely used but little conceptualized notion. Nursing shares a unique and holistic view of patients, yet nursing education, rooted in the substance of nursing, remains undefined. Drawing on the work of English-language theorist Hesook Suzie Kim, this article explains part of her model of nursing practice analysis. This model is composed of four distinct domains that address the need to identify the holistic dimension of nursing knowledge to be taught.


Effects of enzyme loading, densification, and storage on AFEX-pretreated biomass for ethanol production.
Corn stover, switchgrass, and prairie cordgrass were treated with an ammonia fiber expansion (AFEX) process and a novel densification method (ComPAKco). Separate hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF) were used to evaluate impacts of densification. ComPAKco densification is characterized by low-temperature and low-energy requirements, resulting in compacted biomass briquettes (CBB) 1-2 cm square, with a bulk density of 380-460 kg/m(3). Feedstocks were evaluated before and following AFEX pretreatment, after densification, and after storage. Two enzyme doses were tested. The low rate used 5 filter paper units (FPU) of Spezyme CP (cellulase) and 21.3 cellobiase units (CBU) of Novozyme 188 (aka NS50010 [β-glucosidase]) per gram of glucan. The high dosage rate was three times higher and resulted in 40-56 % and 33-82 % higher ethanol yields with SHF and SSF, respectively. Trials revealed no adverse effect on ethanol yield following densification or 6-month storage of densified, AFEX-pretreated feedstocks.


Maternal septicemia with Listeria monocytogenes in second trimester without infection of the fetus.
Two cases of septicemia with Listeria monocytogenes in two pregnant women at the 20th and 23rd weeks of pregnancy, respectively, are presented. The women had delays of 8 and 10 days from onset of symptoms to diagnosis and adequate treatment. Outcome was favorable; both women delivered healthy infants at term.


Occurrence of sickness absence and disability pension in relation to childbirth: A 16-year follow-up study of 6323 Swedish twins.
Pregnancy, delivery, and the postpartum period may imply morbidity leading to work incapacity; however, this is seldom studied. This study aimed to compare twin sisters giving or not giving birth regarding occurrence of sickness absence (SA) and disability pension (DP). This population-based cohort study included all 6323 female twins born in Sweden 1959-1990, using register data for 1994-2010 about SA and DP. Average number of SA/DP days/year was calculated in relation to the year of the first delivery, or, if not giving birth, the year when the twin sister gave birth. Twin pairs discordant for delivery were used to investigate the importance of genetic and environmental factors for occurrence of SA and DP. In all, 52% had a first delivery during 1994-2010. Except for the year of delivery, the average number of SA days/year was similar when comparing women who gave birth to those who did not, while number of DP days was significantly higher in women who did not give birth. Differences between the groups seem attributable to genetic factors. Women who delivered once had higher levels of SA and DP than those who had several deliveries. DP with mental diagnoses was more common among women who had not delivered whereas DP with musculoskeletal diagnoses occurred more often among women who delivered. Levels of SA were similar among women who gave birth and who did not. Women not giving birth had significantly higher levels of DP, indicating health selections into childbirth.


How commonly do US abortion clinics offer contraceptive services?
About half of US women having abortions have already had at least one prior abortion. Facilitating access to contraception may help these women avoid subsequent unintended pregnancies. Information is needed to document the availability of contraceptive services in abortion care settings in the United States. Data for this cross-sectional mixed-methods study were collected between December 2008 and September 2009 and come from two sources: 15 semistructured telephone interviews and 173 structured questionnaires administered to a nationally representative sample of eligible facilities. Respondents were administrators at large (400+ abortions per year), nonhospital facilities that provide abortion services in the United States. Virtually all (96%) abortion clinics incorporate contraceptive education into abortion care, and the three most common methods reported to be distributed are the birth control pill (99%), the vaginal ring (61%) and Depo-Provera (58%). Almost one-third reported being able to offer post-abortion intrauterine device insertion. Most facilities (82%) accept some form of insurance for either contraceptive or abortion services, and those with a broader family planning focus are significantly more likely to do so. Administrators at the majority of facilities (56%) report that patients most commonly do not pay additional fees for contraceptive services because they are included in the cost of abortion services. Although almost all large, non-hospital abortion providers in the United States are able to provide some level of contraceptive care to their abortion patients, the degree to which they are able to do so is influenced by a wide range of factors.


Increased amygdalar metabotropic glutamate receptor 7 mRNA in a genetic mouse model of impaired fear extinction.
Post-traumatic stress disorder (PTSD) is a devastating anxiety-related disorder which develops subsequent to a severe psychologically traumatic event. Only ~ 9% of people who experience such a trauma develop PTSD. It is clear that a number of factors, including genetics, influence whether an individual will develop PTSD subsequent to a trauma. The 129S1/SvImJ (S1) inbred mouse strain displays poor fear extinction and may be useful to model this specific aspect of PTSD. The metabotropic glutamate receptor 7 (mGlu7 receptor) has previously been shown to be involved in cognitive processes and anxiety-like behaviour placing it in a key position to regulate fear extinction processes. We sought to compare mGlu7 receptor mRNA levels in the S1 strain with those in the robustly extinguishing C57BL/6J (B6) inbred strain using in situ hybridisation (ISH) in three brain regions associated with fear extinction: the amygdala, hippocampus and prefrontal cortex (PFC). Compared to the B6 strain, S1 mice had increased mGlu7 receptor mRNA levels in the lateral amygdala (LA) and basolateral amygdala (BLA) subdivisions. An increase was also seen in the hippocampal CA1 and CA3 subregions of S1 mice. No difference in mGlu7 receptor levels were seen in the central nucleus (CeA) of the amygdala, dentate gyrus (DG) of the hippocampus or prefrontal cortex. These data show altered mGlu7 receptor expression in key brain regions associated with fear extinction in two different inbred mouse strains which differ markedly in their fear extinction behaviour. Altered mGlu7 receptor levels may contribute to the deficit fear extinction processes seen in fear extinction in the S1 strain.


catena-Poly[1-[(2-fluoro-benzyl-idene)amino]-quinolinium [plumbate(II)-tri-μ-iodido]].
The title complex, {(C(16)H(12)FN(2))[PbI(3)]}(n), consists of 1-[(2-fluoro-benzyl-idene)amino]-quinolinium cations and a polymeric PbI(3) (-) anion formed by face-sharing PbI(6) octa-hedra. These octa-hedra form straight and regular infinite chains along the b axis. In the asymmetric unit, one cation and one anionic [PbI(3)](-) fragment are observed in general positions. Polymeric chains are produced by the glide plane perpendicular to the a axis.


Effectiveness of mandatory peer review to reduce antipsychotic prescriptions for Medicaid-insured children.
Prior authorization of prescription medications is a policy tool that can potentially impact care quality and patient safety. To examine the effectiveness of a mandatory peer-review program in reducing antipsychotic prescriptions among Medicaid-insured children, accounting for secular trends that affected antipsychotic prescribing nationally. Medicaid Analytical eXtracts (MAX) with administrative claims for health services provided between January 2006 and December 2011. This retrospective, observational study examined prescription claims records from Washington State (Washington) and compared them to a synthetic control drawing from 20 potential donor states that had not implemented any antipsychotic prior authorization program or mandatory peer review for Medicaid-insured children during the study period. This method provided a means to control for secular trends by simulating the antipsychotic use trajectory that the program state would have been expected to experience in the absence of the policy implementation. Before the policy implementation, antipsychotic use prevalence closely tracked those of the synthetic control (6.17 per 1000 in Washington vs. 6.21 in the synthetic control group). Within two years after the policy was implemented, prevalence decreased to 4.04 in Washington and remained stable in the synthetic control group (6.47), corresponding to an approximately 38% decline. Prior authorization program designs and implementations vary widely. This mandatory peer-review program, with an authorization window and two-stage rollout, was effective in moving population level statistics toward safe and judicious use of antipsychotic medications in children.


Extraovarian teratoma with peritoneal gliomatosis.
A 25 year old woman underwent removal of a large, incidentally discovered cul de sac teratoma. It was solid but histologically mature and had given rise to multiple peritoneal implants of mature glial tissue. She was alive without evidence of disease 57 months later. This tumor appears to represent the extraovarian counterpart of previously reported ovarian teratomas with peritoneal gliomatosis.


A method for assessing joint line shift post knee arthroplasty considering the preoperative joint space.
Accurate comparison of outcomes regarding various surgical options in knee arthroplasty can benefit from an improved method for joint line analysis that takes into account the preoperative joint space. This article describes a new preoperative-based registration method that measures changes in the joint line by overlaying the 3D models of the bones with implants using preoperative CT along with preoperative and postoperative biplanar radiography. The method was tested on six cadaveric specimens for measuring alteration to the medial and lateral joint lines in extension and flexion. The joint line shift, when measured using the new method, was in the range of -0.2 to 1.3 mm on average (SD=1.3 to 3.8 mm, for medial and lateral, in flexion and extension positions). This was significantly different (p≤0.01) from the results of a previous postoperative-based registration method which did not account for the cartilage thickness in calculating alterations of the joint line (mean=3.9 to 6.8mm, SD=1.2 to 4.3 mm). These results further highlight the importance of considering the preoperative joint space in analyzing the joint line, and demonstrate the utility of the newly introduced method for accurate assessment of changes in the joint line after arthroplasty. The introduced method provides accurate means for investigating joint line alterations in relation to different surgical techniques and the subsequent biomechanical effects after knee arthroplasty.


Aldehyde modified cellulose-based dual stimuli responsive multiple cross-linked network ionic hydrogel toward ionic skin and aquatic environment communication sensors.
Recently, materials with complicated environmentally-sensitive abilities, high stretchability and excellent conductive sensitivity are interesting actuators in future applications. Herein, we fabricated a versatile and facile polyvinyl alcohol/polyacrylic acid/dialdehyde cellulose nanofibrils-Fe3+ hydrogel integrated with programmable dual-shape memory properties, high mechanical strength, good recoverability, and heat-induced self-healing capability. Benefiting from the synergistic effect of hydrogen bonds and dual metal coordination bonds of cellulose-based dialdehyde and carboxyl with Fe3+and then heating-freeze-thawing cycle treatment, the obtained hydrogel exhibited dual shape memory abilities, high tensile strain (up to 600 %), good self-recovery, and anti-fatigue properties. Moreover, the resultant hydrogel sensors showed revealed high strain sensitivity (gauge factor = 2.95) and satisfactory electrochemical performance; and such hydrogel-based sensor could be used as ionic skin to detect various human motions in real-time and barrier-free communication in the aquatic environment. The composite hydrogel with superior and versatile performances reported in this study could offer a great promise to be applied under extreme conditions as multifunctional sensors.


The pharmacokinetic interaction between irinotecan and sunitinib.
The previous clinical trials found that the co-administration of irinotecan with sunitinib exhibited a synergistic antitumor effect. In the current study, we aimed to investigate whether the synergistic effect is related to a potential pharmacokinetic interaction between sunitinib and irinotecan. The inhibitory effects of sunitinib on SN-38 glucuronidation were determined by measuring the formation rates for SN38 glucuronide using recombinant human UGT isoforms and human liver microsomes (HLMs) in the absence or presence of sunitinib. Our data indicated that sunitinib exhibited competitive inhibition against SN-38 glucuronidation by UGT1A1, but inhibitory effects of sunitinib were weak in pooled human liver microsomes (HLMs) (Ki = 119.00 μM) and recombinant UGT1A1 (Ki = 42.71 μM). Our further prediction study partly explains the possible mechanism of synergistic antitumor activity of sunitinib and irinotecan in the combined treatment and provides a basis for design of clinical studies for the development and optimization of this combination.


A unique case of der(11)t(11;22),-22 arising from 3:1 segregation of a maternal t(11;22) in a family with co-segregation of the translocation and breast cancer.
To report the first tertiary monosomy in a pregnancy loss to a female t(11;22) carrier. The patient was a 34-year-old G10P1 female known to have a balanced translocation t(11;22)(q23;q11.2). She had one female livebirth (a translocation carrier) and eight miscarriages. Five female relatives known to be translocation carriers had a history of breast cancer, three of them premenopausally. The patient herself had a malignant melanoma. During the 10th pregnancy, ultrasound showed a viable embryo at 6 weeks of gestation, but loss of embryonic heartbeat by 7.5 weeks. Culture of the products of conception at 8 weeks of gestation showed the karyotype: 46,XY,+2,der(11)t(11;22)(q23;q11.2)mat,-22[4]/45,XY,der(11)t(11;22)(q23;q11.2)mat,-22[4], resulting from fertilization of the maternal 3:1 segregation product containing only the der(11) by a normal gamete. Subsequently, she became pregnant with a normal 46,XX fetus. FISH analysis indicated that the breakpoints on 11q and 22q in the patient were in the previously described region common to typical recurrent t(11;22). In addition, a nested-PCR-based approach showed that they were located within the same palindromic AT-rich sequence previously described. This case demonstrates that the tertiary monosomy resulting from the 3:1 segregation is compatible with embryonic survival into the first trimester. It is also another example of apparent association of the constitutional translocation t(11;22) and breast cancer.


TMS-induced inhibition of the left premotor cortex modulates illusory social perception.
Communicative actions from one person are used to predict another person's response. However, in some cases, these predictions can outweigh the processing of sensory information and lead to illusory social perception such as seeing two people interact, although only one is present (i.e., seeing a Bayesian ghost). We applied either inhibitory brain stimulation over the left premotor cortex (i.e., real TMS) or sham TMS. Then, participants indicated the presence or absence of a masked agent that followed a communicative or individual gesture of another agent. As expected, participants had more false alarms in the communicative (i.e., Bayesian ghosts) than individual condition in the sham TMS session and this difference between conditions vanished after real TMS. In contrast to our hypothesis, the number of false alarms increased (rather than decreased) after real TMS. These pre-registered findings confirm the significance of the premotor cortex for social action predictions and illusory social perception.


Is nondirectiveness possible within the context of antenatal screening and testing?
Partly in order to dissociate itself from eugenics, genetic counselling values the principle of nondirectiveness as a key feature. Recent reports have upheld the importance of this approach, treating it unproblematically. However, doubts have been expressed about whether nondirective counselling is possible or indeed, desirable. Changes in organisational aspects of antenatal screening delivery in the UK have meant that genetic counselling is now being carried out by a variety of practitioners other than counsellors and specialists. These are often practitioners such as obstetricians and midwives who, in many other aspects of their work do not practise in a nondirective way. This paper explores some of the difficulties health practitioners encountered when attempting to work nondirectively. Reasons given by practitioners for not following this approach fell into categories, which in turn formed a continuum. Categories along the continuum ranged from acting directively at the request of women, through to deciding for women, either covertly or overtly, in their "best interests". It appears that for practitioners, the boundary between choice and coercion is not a clearcut one, and visualising it instead as a continuum may make it easier to see how slippage between choice and coercion can occur. The paper highlights the dilemmas which a variety of practitioners are dealing with in their daily work, in the hope of encouraging debate about these complex clinical and ethical issues.


Infection during childhood and the risk of violent criminal behavior in adulthood.
Infections during brain development appear to contribute to cognitive impairment and aggressive behavior, as well as to a number of developmental mental disorders closely associated with violent criminal behavior. Yet, no study has thus far ever investigated whether infections during brain development increases the risk of violent criminality later in life. In this population-based cohort study, about 2.2 million individuals born in Sweden between the years 1973 and 1995 were included in an effort to estimate the association between infections during childhood (registered ICD-10 diagnoses of infections incurred before the age of 14 years) and violent criminal behavior (registered convictions for a violent crime between the ages of 15 and 38 years, prior to December 31, 2011). After inclusion of several sociodemographic parameters, risks of violent criminal behavior conferred by childhood infections - expressed as hazard ratios (HRs) and 95% confidence intervals (CIs) - were calculated by means of Cox regression. Mediation analyses were performed to explore the effect of psychiatric disorders on the association between infections during childhood and violent criminality. Results revealed a modest, yet significant, association between an infection during childhood and violent criminality later in life (adjusted HR 1.14, 95% CI 1.12-1.16). Infections during the first year of life and infections in the central nervous system were associated with the highest risks of subsequent violent criminality (adjusted HR 1.20, 95% CI 1.18-1.23, and adjusted HR 1.17, 95% CI 1.08-1.26, respectively). The association was partly mediated by the presence of a psychiatric disorder. In summary, independent of a wide range of covariates, our results suggest that infections during brain development could be part of the genesis of violent criminal behavior.


Rhodamine 123 inhibits bioenergetic function in isolated rat liver mitochondria.
Rhodamine 123 accumulates in the mitochondria of living cells and exhibits selective anticarcinoma activity. The biochemical basis of toxicity was investigated by testing the effect of the dye on isolated rat liver mitochondria. Much lower concentrations of rhodamine 123 were required to inhibit ADP-stimulated respiration and ATP synthesis in well-coupled energized mitochondria than were required to inhibit uncoupled respiration and uncoupler-stimulated ATP hydrolysis. The amount of rhodamine 123 associated with the mitochondria was several-fold greater under energized as compared to non-energized conditions, which may explain why coupled functions appeared to be more sensitive than uncoupled functions to inhibition at low concentrations of rhodamine 123. It was concluded that the site of rhodamine 123 inhibition is most likely the F0F1 ATPase complex and possibly electron transfer reactions as well.


Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure.
We investigated the prognostic relevance of serpin peptidase inhibitor, clade A member 3 (SERPINA3) in patients admitted with a de novo or worsened heart failure (HF). In the first stage, 83 HF-related left ventricular (LV) transcripts were examined in patients with congestive cardiomyopathy (CCMP, n = 44) who died within 5 years and compared with age-matched and haemodynamically matched CCMP survivors (n = 39) and controls with normal LV function (n = 17). Among 14 differentially expressed transcripts, myocardial gene and circulating SERPINA3 levels were up-regulated in non-survivors vs. survivors (2.40 ± 3.66 vs. 0.36 ± 0.22 units, P < 0.01 and 334.7 ± 138.7 vs. 228.2 ± 83.1 μg/mL, P < 0.01, respectively). While no significant transmyocardial gradient was detected, cytokine stimulation of human endothelial cells induced SERPINA3 secretion. In an independent validation cohort with a de novo or worsened HF (n = 387), circulating SERPINA3 levels > 316 μg/mL were associated with increased all-cause mortality {hazard ratio [HR] [95% confidence interval (CI)]: 2.4 [1.5-3.9], P = 0.0002} and its composite with unplanned cardiovascular readmission [HR (95% CI): 2.0 (1.2-3.3), P = 0.004]. Patients with elevated SERPINA3 levels and elevated either N-terminal pro brain natriuretic peptide or ST2 showed worse freedom from both endpoints. In a multivariate analysis, including established clinical risk factors, SERPINA3 remained independent predictor of all-cause mortality together with age, gender, ST2, glomerular filtration, and pulmonary capillary wedge pressure. In patients with a de novo or worsened HF, increased SERPINA3 levels > 316 μg/mL are associated with increased mortality or unplanned cardiac readmission. Elevated SERPINA3 levels on top of established clinical predictors appear to identify a subgroup of HF patients at higher mortality risk. Prospective studies should further validate its value in prognostic stratification of HF.


Risk of incident cardiovascular events with disease-modifying anti-rheumatic drugs among adults with rheumatoid arthritis: a nested case-control study.
This study examined the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). This nested case-control study used the MarketScan database (2012-2014), involving adult RA patients (aged ≥18 years) initiating either a conventional synthetic (cs) DMARD, biologic DMARD, or targeted synthetic (ts) DMARD between January 1, 2013 and December 31, 2014 (cohort entry) and had no CVD history. Cases were individuals with incident CVD identified using diagnosis codes or procedure codes from medical claims. For each case, 10 age- and sex-matched controls were selected using the incident density sampling with replacement. Prescriptions of DMARDs were measured 90 days before the event date. Conditional logistic regression examined the association of risk of CVD with DMARDs in combination treatment or individual use, with reference to methotrexate (MTX) monotherapy, adjusting for baseline confounders. Subgroup analyses were performed separately in DMARD combination therapy users or individual DMARD users, respectively. In total, 270 cases of incident CVD and 2700 controls were included (mean [standard deviation (SD)] age: 54 [1]; 75.6% women). The commonly prescribed DMARD therapies were csDMARD monotherapy (n = 795, 27.04%), followed by tumor necrosis factor inhibitors (TNFi) monotherapy (n = 367, 12.48%), and TNFi in combination with MTX (n = 314, 10.68%). Compared with MTX monotherapy, overall use of DMARD agents was not associated with the differential risk of CVD, including various types of DMARD combination regimens. The findings were similar across subgroup analyses. The study found no differential risk of CVD with DMARDs in combination therapy or monotherapy compared to MTX monotherapy in patients with RA. Key Points • This study evaluated the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). • Findings suggest no differential CVD risk with DMARDs in combination with MTX or used individually compared with MTX monotherapy in patients with early RA. • Further efforts should focus on a better understanding of the mechanism of DMARD combination treatments with MTX in modifying CV risk.


Peripheral dysplasia. Report of a new genetic syndrome.
A new, dominantly inherited form of peripheral dysplasia in three members of an Algerian family is reported. Two further individuals, not investigated, are also probably affected. The disease is characterised by distinctive clinico-radiological findings. A case of acromesomelic dysplasia of Maroteaux is also reported and the differential diagnosis of peripheral dysplasias is discussed.


Prognostic values of a combination of intervals between respiratory illness and onset of neurological symptoms and elevated serum IgM titers in Mycoplasma pneumoniae encephalopathy.
To retrospectively analyze the clinical manifestations of Mycoplasma pneumoniae (M. pneumoniae)-associated encephalopathy in pediatric patients. Pediatric patients with positive serum anti-M. pneumoniae immunoglobulin M (IgM) were enrolled in this study. Clinical signs and symptoms, laboratory data, neuroimaging findings, and electrophysiological data were reviewed. Of 1000 patients identified, 11 (1.1%; male:female ratio = 7:4) had encephalopathy and were admitted to the pediatric intensive care unit. Clinical presentation included fever, symptoms of respiratory illness, and gastrointestinal upset. Neurological symptoms included altered consciousness, seizures, coma, focal neurological signs, and personality change. Neuroimaging and electroencephalographic findings were non-specific. Specimens of cerebrospinal fluid (CSF) for M. pneumoniae polymerase chain reaction (PCR) were negative. Higher M. pneumoniae IgM titers and longer intervals between respiratory and CNS manifestations were associated with worse outcomes. Clinical manifestations of M. pneumoniae-associated encephalopathy were variable. Diagnosis of M. pneumoniae encephalopathy should not rely on CSF detection of M. pneumoniae by PCR. M. pneumoniae IgM titers and intervals between respiratory and CNS manifestations might be possibly related to the prognosis of patients with M. pneumoniae-associated encephalopathy.


Chromosome banding in Amphibia. XVIII. Karyotype evolution and genomic size variation in Pleurodema (Anura, Leptodactylidae).
DNA flow cytophotometric measurements demonstrate that the quantity of nuclear DNA of the South American leptodactylid frog Pleurodema brachyops is 3.4 times greater than that of P. thaul. Nevertheless, the conventionally stained karyotypes of both species are nearly identical. In the metaphase chromosomes of P. brachyops, the chromatin has a distinctly higher degree of packaging than in those of P. thaul. C-banding reveals that almost 6 times the constitutive heterochromatin is present in the karyotype of P. brachyops than in the karyotype of P. thaul. Analysis of fluorescence banding patterns shows that the chromosomes of P. brachyops contain AT- and GC-rich heterochromatin, whereas the karyotype of P. thaul is devoid of brightly fluorescing heterochromatin. The substantial differences in the genome sizes of Pleurodema is explained by homogeneous, symmetrical changes in the amounts of all DNA sequence classes along all chromosomes, which preserved the ancestral morphology of the chromosomes.


Screening, characterization and specific binding mechanism of aptamers against human plasminogen Kringle 5.
Plasminogen Kringle 5 is one of the most potent cytokines identified to inhibit the proliferation and migration of vascular endothelial cells. Herein, six aptamer candidates that specifically bind to Kringle 5 were generated by the systematic evolution of ligands by exponential enrichment (SELEX). After 10 rounds of screening against Kringle 5, a highly enriched ssDNA pool was sequenced and the representative aptamers were subjected to binding assays to evaluate their affinity and specificity. The preferred aptamer KG-4, which demonstrated a low dissociation constant (Kd) of ∼ 432 nM and excellent selectivity for Kringle 5. A conserved "motif" of eight bases located at the stem-loop intersection, common to the aptamer, was further confirmed as the recognition element for binding with Kringle 5. The bulge formed by the motif and depression on the lysine binding site of Kringle 5 were both located at the binding interface, and the "induced fit" between their structures played a central role in the recognition process. Kringle 5 interacts KG-4 primarily through enthalpy-driven van der Waals forces and hydrogen bond. The key nucleotides A34 and C35 at motif on KG-4 and the positively charged amino acids in the loop 1 and loop 4 regions on Kringle 5 play a major role in the interaction. Furthermore, KG-4 dose-dependently reduced the proliferation inhibition of vascular endothelial cells by Kringle 5 and had a blocking effect on the function of Kringle 5 in inhibiting migration and promoting apoptosis of vascular endothelial cells in vitro. This study put a new light on protein-aptamer binding mechanism and may provide insight into the treatment of ischemic diseases by target depletion of Kringle 5.


[Causes of non-use of postpartum contraceptive method among adolescent mothers].
To determine the causes of non postpartum contraceptive use among adolescent mothers. We conducted a cross-section descriptive study. We included women who asked for attention of an obstetric event in 2002, we identified those were in immediate postpartum period, and we selected those that did not began a birth-control method. Data were collected directly with an interview and revision of the file, later on they were coded and processed manually; the causes of non contraceptive use were classified in: attributable causes to patient: personal, religious, moral, familiar, cultural, etc. Reasons, when they received information and advice or when they did not assist to educational actions; attributable causes to hospital: technique administrative factors, insufficient educational communication activities by service provider; and attributable causes to medical indication: presence of risk factors for health women. The statistical analysis was carried out using frequencies and percentages. We found 261 women, we identified 160 (61%) in immediate postpartum period, 52 (32%) they did not began contraceptive use. The causes of non postpartum contraceptive use among adolescent mothers were attributable to themselves in 75%, in 21% to the medical unit, and 4% to medical indication.


Free carnitine and acetyl carnitine plasma levels and their relationship with body muscular mass in athletes.
The purpose of the present study was to investigate the relationship between plasma carnitine concentration and body composition variation in relation to muscular and fat masses since there is no experimentally proved correlation between plasma carnitine and body masses. We used bioelectric impedance analysis (BIA), to determine body composition and to have a complete physical fitness evaluation. The post-absorptive plasma free carnitine and acetyl carnitine plasma levels, body composition as Fat-Free Mass (FFM) and Fat Mass (FM) in kg, as well as in percent of body mass, were analysed in 33 healthy subjects. A significant negative correlation was found between plasma acetyl carnitine and FFM in weight (kg) as well as in percent of body mass (respectively p < 0.0001; p < 0.01); a significant positive correlation was found only between FM in percent and plasma acetyl carnitine (p < 0.01). The observed negative correlation between plasma acetyl carnitine and muscular mass variation might reflect an oxidative metabolic muscle improvement in relation to muscular fat free mass increment and might be evidence that muscle metabolism change is in relation to plasma acetyl carnitine concentration.


[Salvage portacaval shunts after failure of intrahepatic shunt].
Creation of an intrahepatic shunt using a metallic prosthesis introduced via a transjugular approach constitutes an alternative to surgery in the treatment of portal hypertension. Although rare, the specific complications of this technique justify close collaboration between radiologists and surgeons. The authors report two serious complications after failure of intrahepatic shunt, requiring emergency laparotomy.


Estimating the Binding of Sars-CoV-2 Peptides to HLA Class I in Human Subpopulations Using Artificial Neural Networks.
Epidemiological studies show that SARS-CoV-2 infection leads to severe symptoms only in a fraction of patients, but the determinants of individual susceptibility to the virus are still unknown. The major histocompatibility complex (MHC) class I exposes viral peptides in all nucleated cells and is involved in the susceptibility to many human diseases. Here, we use artificial neural networks to analyze the binding of SARS-CoV-2 peptides with polymorphic human MHC class I molecules. In this way, we identify two sets of haplotypes present in specific human populations: the first displays weak binding with SARS-CoV-2 peptides, while the second shows strong binding and T cell propensity. Our work offers a useful support to identify the individual susceptibility to COVID-19 and illustrates a mechanism underlying variations in the immune response to SARS-CoV-2. A record of this paper's transparent peer review process is included in the Supplemental Information.


Therapeutic approaches of asthma and COPD overlap.
Asthma and COPD overlap (ACO) is an important clinical phenotype, due to the low-health-related quality of life (QOL), rapid decline in lung function, frequent exacerbation, and high economic burden. However, no large-scaled therapeutic trials of ACO have been conducted. At present, ACO is treated according to asthma/COPD guidelines. The goals of ACO treatment are to relieve symptoms and improve QOL and lung functions. Treatment must also prevent disease progression, airway remodeling, exacerbation, complications, and comorbidities. To achieve these goals, ACO needs first to be assessed based on pathophysiological findings. Comprehensive long-term management includes medication, reduction of risk factors, environmental improvement, patient education, rehabilitation, and vaccination. Drug treatment for ACO employs a combination of inhaled corticosteroids (ICSs) and long-acting bronchodilators; long-acting muscarinic antagonists and/or long-acting β2-agonists. The dose of ICS is determined according to ACO severity. Leukotriene receptor antagonists and theophylline are used as add-on drugs. Macrolides and expectorants are recommended for reduction of mucus hypersecretion. Anti-IgE and anti-IL-5 antibodies, oral corticosteroids, and oxygen therapy are additional treatments for the most severe ACO. The therapeutic effects are evaluated using lung function tests, eosinophil counts in sputum and blood, FeNO, and symptom questionnaires. ACO exacerbation is treated by inhalation of short-acting β2-agonist and systemic corticosteroids. The doses of corticosteroids are determined based on the asthma/COPD component of the exacerbation. Administration of antibiotics is recommended if sputum is purulent. Referral to specialists is necessary in cases of inability to control symptoms by medication, uncertain diagnosis with atypical features, or severe complications and comorbidities.