Influenza virus infections in infants.
Universal immunization of children with live attenuated cold recombinant vaccine has been proposed. The renewed recommendation for maternal immunization with influenza vaccine should increase the amount of antibody transmitted to the infant and postpone the need for active immunization. This study examines the risk of influenza during the first year of life to provide information about the time to initiate active immunization. Infants followed from birth to 1 year of age in the Houston Family Study were monitored weekly for influenza virus infection. Serum specimens were tested for evidence of infection at 4-month intervals. One-third of 209 infants were infected during the first year; most of the infections occurred during the second 6 months of life. Only 26 of 69 infections were detected before 6 months of age compared with 43 afterward. More striking was the concentration of serious illnesses in the latter half of the first year; 8 of 9 otitis media episodes and 9 of 11 lower respiratory tract illnesses occurred in the older infants. The combination of increased maternal antibody titers that should result from influenza immunization and the lesser risk of influenza in the first 6 months of life allows initiation of active immunization of children after 6 months of age.


Exploring response signals and targets in aggressive unresectable hepatocellular carcinoma: an analysis of targeted therapy phase 1 trials.
Patients with advanced hepatocellular carcinoma (HCC) have limited effective therapeutic options. Given the rapid advanced in drug development and emergence of novel agents, we analyzed the characteristics and outcomes of HCC patients treated on early phase trials with an emphasis on targeted therapies. We reviewed the records of consecutive HCC patients evaluated in the Phase I Clinical Trials Program at MD Anderson from March 2004. Thirty-nine patients were not treated due to poor performance status (n = 22, 56%) and decision to pursue alternate therapies (n = 10, 27%). Of 61 treated patients (median age, 60 years; median prior therapies, 3), eight patients (13%) attained stable disease lasting ≥6 months; four (7%) had a partial response, mainly with anti-angiogenic or multikinase inhibitors. Median Phase I progression-free survival (PFS) was 2.6 months versus 4.4 months (p 0.019) and 4.1 months (p 0.27) for their first-, and second-line FDA-approved therapy. Molecular analysis showed frequent PTEN loss (10/19 patients, 53%) and P53 mutation (4/4 patients tested). On multivariate analysis, independent factors predicting shorter survival were white ethnicity/race (p 0.031), cirrhosis (p 0.016), and serum sodium (p 0.0013). In our heavily-pretreated HCC patients, the phase I PFS was comparable to that of 2nd-line therapy, highlighting a potential role for clinical trials after progression on first-line therapy. The response rate (SD>6 months/PR) of 20% was observed with early signals of activity in regimens combining inhibitors of angiogenesis, multiple kinases and mTOR with preliminary molecular analysis revealing prevalence of PTEN loss.


Cutaneous dental sinus tract, a common misdiagnosis: a case report and review of the literature.
Cutaneous sinus tracts of dental origin are often initially misdiagnosed and inappropriately treated because of their uncommon occurrence and the absence of symptoms in approximately half the individuals affected. Patients are often referred with a recurrent or chronic cyst, a furuncle, or an ulcer on the face or neck. Correct diagnosis is based on a high index of suspicion and on radiologic evidence of a periapical root infection. Appropriate treatment results in predictable and rapid healing of these lesions. We present a case report of this common misdiagnosis and a review of the literature with regard to diagnosis and treatment.


Conjoint and dissociable effects of syntactic and semantic context.
Manipulating the semantic relatedness of noun and verb targets in contexts where they are grammatically appropriate or inappropriate allows for simultaneous examination of syntactic and semantic context effects. A lexical-decision experiment showed both a syntactic context effect and a semantic relatedness effect that was stronger in syntactically appropriate conditions. Thus, latencies appeared to be conjointly determined by syntactic and semantic context. In contrast, naming experiments also showed both semantic and syntactic effects, but the syntactic context effect was independent of semantic relatedness and was observed in the virtual absence of sensitivity to semantic anomaly. Thus, syntactic and semantic processing are largely dissociable in the naming task. In conjunction with other findings in the literature, this suggests the existence of an isolable level of syntactic assignment that precedes semantic integration of content words in sentence comprehension.


Osteoporosis: prevention and implications for social work practice and policy.
Osteoporosis is one of the major disorders of our time and is increasing at an alarming rate. It affects over 10 million women in the United States and is expected to affect 14 million by the year 2020. There are a number of risk factors for osteoporosis that are of a modifiable nature; however, many women do not take the necessary precautions to prevent the disease. The reasons that women do not actively engage in preventative and remedial strategies to deal with the potential for osteoporosis are complex. It is clear that women must have adequate knowledge to make informed decisions regarding osteoprotective behaviors. Social workers are in a unique position to provide interventions not only on a micro level (educating individual clients) but also on a macro level in terms of large-scale education campaigns focusing on nutrition and exercise both in children and in adults. This article examines the reasons for the failure of women to engage in osteoprotective behaviors by exploring barriers to prevention and their impact on social work policy, practice, and research.


Efficacy of platinum drugs in the treatment of elderly patients with advanced non-small cell lung cancer and their effects on prognosis and survival.
This study aimed to investigate the efficacy of platinum drugs in the treatment of elderly patients with advanced non-small cell lung cancer (NSCLC) and their effects on prognosis and survival. A retrospective analysis was performed on the medical records of 128 elderly patients with stage IV NSCLC admitted to Yan'an Affiliated Hospital of Kunming Medical University from January 2015 to February 2016, who were distributed to a combination group (70 patients) and a control group (58 patients) according to chemotherapy. The efficacy was evaluated after 5 cycles of chemotherapy, and the expression levels of cytokeratin 19 fragment antigen (CYFRA21-1) and carcinoembryonic antigen (CEA) before and after chemotherapy were recorded. Patients in the two groups were followed up. Serum CYFRA21-1 and CEA expression levels in the combination group were lower than those in the control group after 3 and 5 cycles of chemotherapy (p<0.05). According to the Response Evaluation Criteria in Solid Tumors (RECIST), after 3 cycles of chemotherapy there were more patients with complete response (CR) and partial response (PR) in the combination group than those in the control group (p<0.05); after 5 cycles of chemotherapy, patients with CR in the combination group were more than those in the control group (p<0.05). According to CYFRA21-1 and CEA expression levels after 5 cycles of chemotherapy, the patients were separated to a high expression group with a median survival time of 19 weeks and a low expression group with a median survival time of 26 weeks, with a statistically significant difference between the two groups (c2=5.617, p=0.018). In conclusion, platinum drugs are effective in the treatment of elderly patients with advanced NSCLC, which prolong their survival and improve their quality of life, and therefore are worthy of clinical promotion.


Chemical carcinogenesis. I. Rat liver tRNA ethylation by ethionine.
The mechanism of biological action of the powerful carcinogen ethionine is still unknown at the present. Here the "in vivo" tRNA ethylation after administration of radioactive ethionine to rats has been reinvestigated. In particular, the radioactive "pyrimidine nucleotides" fraction was examined: chromatographic and ultraviolet-spectral analyses indicated the presence of imidazole-ring-opened derivatives of guanosine in this fraction, the identification of which is reported in the accompanying paper. These data appear particularly interesting especially when considering the recently advanced hypothesis (6,7) of a transversion purine----pyrimidine as the initial precancerous biochemical lesion in chemical carcinogenesis.


Drug-induced gingival hyperplasia.
Gingival hyperplasia refers to an overgrowth of gum tissue. It starts in the anterior interdental tissues and then extends posteriorly. The gums can sometimes enlarge to cover almost all the teeth. The hyperplastic tissue appears to be fibrous. The consequences are mainly cosmetic. Gingival hyperplasia can be caused by a number of drugs, generally during long-term use.


Health effects of dioxin exposure: a 20-year mortality study.
Follow-up of the population exposed to dioxin after the 1976 accident in Seveso, Italy, was extended to 1996. During the entire observation period, all-cause and all-cancer mortality did not increase. Fifteen years after the accident, mortality among men in high-exposure zones A (804 inhabitants) and B (5,941 inhabitants) increased from all cancers (rate ratio (RR) = 1.3, 95% confidence interval (CI): 1.0, 1.7), rectal cancer (RR = 2.4, 95% CI: 1.2, 4.6), and lung cancer (RR = 1.3, 95% CI: 1.0, 1.7), with no latency-related pattern for rectal or lung cancer. An excess of lymphohemopoietic neoplasms was found in both genders (RR = 1.7, 95% CI: 1.2, 2.5). Hodgkin's disease risk was elevated in the first 10-year observation period (RR = 4.9, 95% CI: 1.5, 16.4), whereas the highest increase for non-Hodgkin's lymphoma (RR = 2.8, 95% CI: 1.1, 7.0) and myeloid leukemia (RR = 3.8, 95% CI: 1.2, 12.5) occurred after 15 years. No soft tissue sarcoma cases were found in these zones (0.8 expected). An overall increase in diabetes was reported, notably among women (RR = 2.4, 95% CI: 1.2, 4.6). Chronic circulatory and respiratory diseases were moderately increased, suggesting a link with accident-related stressors and chemical exposure. Results support evaluation of dioxin as carcinogenic to humans and corroborate the hypotheses of its association with other health outcomes, including cardiovascular- and endocrine-related effects.


Biomarkers as tools in human health risk assessment.
Evaluation of occupational or environmental risk due to exposure to chemicals requires sufficient information on the toxic profiles, mechanisms of action, toxicokinetics, dose-response relation, exposure, and the target dose. Usually exposure is estimated by measuring concentrations of the agent in air, food, water, soil, dust, or other media with which a population or an individual is in contact. However, this external exposure is only a rough estimate for the internal exposure (agent dose or its metabolite at the critical target in the organism). Factors of influence are bioavailability of the chemicals, variations in concentrations and routes of exposure, physical activity, and individual variation in rates of metabolism, distribution, and excretion. All these affect the concentration of the toxic agent at the critical target, which is the most precise information for risk assessment. Thus, internal exposure is best measured by determining the concentration of the toxicant or its ultimate metabolite at the critical site in the target organ or by determining adducts with cellular macromolecules such as proteins, amino acids, DNA, or its bases. The latter are easily available in experimental toxicology from animal experiments but only occasionally from humans. For health surveillance such data usually are not available, because they require invasive procedures such as biopsies. Therefore, more accessible body fluids or tissue are used, such as blood, urine, or adipose tissue, or adducts with macromolecules such as albumin or hemoglobin in the blood, DNA adducts in peripheral lymphocytes, or altered DNA bases in urine such as 8-hydroxyguanine. All of these are indicators for exposure, whereas risk can only be estimated if the correlation between their deviations from normal and the dose-response at the critical target is known.


A rare chromosomal disorder - isochromosome 18p syndrome.
Tetrasomy 18p is a very rare chromosomal disorder and is the result of a spontaneous mutation early in embryonic development in most of the cases. This condition is characterised by the presence of a supernumerary 18p isochromosome (i(18p)) in all or some cells of the affected individual. It has a prevalence of 1/180000 live births and affects both genders equally. In this paper we report a de novo tetrasomy 18p in a 3 months old female dysmorphic child. The clinical features were distinctive with a particular facies, strabismus, microcephaly, growth delay, neonatal hypertonia and talipes varus. An additional small metacentric marker chromosome has been identified after standard cytogenetic analysis, without recognized parental origin of the supplementary genetic material. The child's parents were also tested and their karyotype results were normal. The characterization of the marker chromosome was performed in our genetics laboratory using conventional cytogenetic methods and Fluorescence in Situ Hybridization (FISH) analysis. Also, our patient was compared with other published cases with the same diagnosis. Cytogenetic investigation is an essential step towards the accurate diagnosis of individuals with clinical suspicion of a genetic anomaly. Also, this type of investigation could offer critical information to the practitioner for prognosis of patient and the correct appreciation of the recurrence risk of a certain genetic condition.With current advances in preventive and interventional procedures, patients with rare chromosomal disorders can live longer. Therefore, proper medical and behavioural management of each case is important for the enhancement of the quality of life for the patients and their families.


Validation of the medical outcomes study HIV (MOS-HIV) health survey among HIV-infected patients in Taiwan.
To examine both the reliability and the validity of the 'Medical Outcomes Study HIV' (MOS-HIV) health survey among HIV-infected patients in Taiwan. Data were collected from 619 HIV-infected outpatients, with the reliability and the validity of the MOS-HIV survey subsequently being examined by multi-trait scaling techniques, internal consistency, convergent validity, known-group validity and factorial validity. The MOS-HIV health survey was found to have excellent success rates in the item-consistency and discriminant-validity tests, as well as good convergent validity and known-group validity. An acceptable fit was found for three of the four indices in the original two-factor model (non-normed fit index = 0.92, comparative fit index = 0.94 and standardized root mean squared residual = 0.056). The findings of the present study provide strong evidence in support of the reliability and validity of the MOS-HIV health survey for the assessment of quality of life among HIV-infected patients in Taiwan. We find that the original factor structure of the MOS-HIV survey remains valid for patients from Chinese cultural backgrounds. This study therefore contributes to the existing evidence within the extant literature on the cultural relevance of the MOS-HIV health survey (a measure originally developed within a Western culture) as a valid measure for cross-cultural comparative studies on health-related quality of life.


Thoracoscopic lobectomy for treating cancer in a patient with an unusual vein anomaly.
Various anatomical variants in pulmonary veins can have a serious effect on patients undergoing lung surgery. We present a case of a patient with an unusual pulmonary vein variation. Preoperative review of the patient's three-dimensional 64-row multidetector computed tomography imaging allowed us precise simulation and good orientation of the patient's vascular variant anatomy during surgery. Upper lobectomy through thoracoscopic approach was performed successfully in the case where the middle lobe vein might have been divided without preoperative anatomical evaluation by 3D CT images.


Association Between African American Race and Clinical Outcomes in Men Treated for Low-Risk Prostate Cancer With Active Surveillance.
There is concern that African American men with low-risk prostate cancer may harbor more aggressive disease than non-Hispanic White men. Therefore, it is unclear whether active surveillance is a safe option for African American men. To compare clinical outcomes of African American and non-Hispanic White men with low-risk prostate cancer managed with active surveillance. Retrospective cohort study in the US Veterans Health Administration Health Care System of African American and non-Hispanic White men diagnosed with low-risk prostate cancer between January 1, 2001, and December 31, 2015, and managed with active surveillance. The date of final follow-up was March 31, 2020. Active surveillance was defined as no definitive treatment within the first year of diagnosis and at least 1 additional surveillance biopsy. Progression to at least intermediate-risk, definitive treatment, metastasis, prostate cancer-specific mortality, and all-cause mortality. The cohort included 8726 men, including 2280 African American men (26.1%) (median age, 63.2 years) and 6446 non-Hispanic White men (73.9%) (median age, 65.5 years), and the median follow-up was 7.6 years (interquartile range, 5.7-9.9; range, 0.2-19.2). Among African American men and non-Hispanic White men, respectively, the 10-year cumulative incidence of disease progression was 59.9% vs 48.3% (difference, 11.6% [95% CI, 9.2% to 13.9%); P < .001); of receipt of definitive treatment, 54.8% vs 41.4% (difference, 13.4% [95% CI, 11.0% to 15.7%]; P < .001); of metastasis, 1.5% vs 1.4% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .49); of prostate cancer-specific mortality, 1.1% vs 1.0% (difference, 0.1% [95% CI, -0.4% to 0.6%]; P = .82); and of all-cause mortality, 22.4% vs 23.5% (difference, 1.1% [95% CI, -0.9% to 3.1%]; P = 0.09). In this retrospective cohort study of men with low-risk prostate cancer followed up for a median of 7.6 years, African American men, compared with non-Hispanic White men, had a statistically significant increased 10-year cumulative incidence of disease progression and definitive treatment, but not metastasis or prostate cancer-specific mortality. Longer-term follow-up is needed to better assess the mortality risk.


Symptomatic plate removal in maxillofacial trauma: a review of 76 cases.
This study reviewed the fate of titanium plates used to correct maxillofacial trauma in 76 patients to define risk factors for plate removal. Medical records of 76 consecutive patients at a single institution, over a 10-year period, were retrospectively reviewed. Variables included age, sex, trauma type, diagnosis, fracture type, fracture diagnosis, plate location, surgical approach, and reasons for plate removal. Fracture diagnosis was described as panfacial (42%), blowout (3%), midface (28%), zygoma (26%), mandible angle (6%), ramus (7%), and symphysis (9%). All plate removals according to fracture diagnosis were in the mandible angle (30%) and symphysis (20%). When plate location was reviewed, 68% of the plates were placed in the upper and midface and 32% were placed in the mandible. Specifically, plates were placed in the frontozygomatic suture (18%), zygomaticomaxillary suture (19%), infraorbital rim (14%) and mandible symphysis (15%), mandible angle (9%), piriform (6%), nasal (5%), mandible ramus (4%) and body (4%), zygoma (2%), and frontal (2%). Of 163 plates that were placed, 6 plates (3.7%) were removed. Three (12%) of the symphysis plates and 3 (20%) of the angle plates were removed. Among all variables, only fracture diagnosis (P = 0.01) and plate location (P = 0.01) were statistically significant in plate removal. Five plates were removed for abscess/infection; 1 plate was removed for osteomyelitis. Further review revealed that 4 out of 6 plates removed involved synchronous mandible fractures. Most infections after maxillofacial trauma occur in the mandible, and often these infections are the main reason for plate removal. More vigilance is needed in the treatment of mandible angle and symphyseal fractures, especially if there are synchronous fractures, to prevent infection, plate removal and subsequent malunion.


Secnidazole Is a Promising Imidazole Mitigator of Serratia marcescens Virulence.
Serratia marcescens is an opportunistic pathogen that causes diverse nosocomial infections. S. marcescens has developed considerable resistance to different antibiotics and is equipped with an armory of virulence factors. These virulence factors are regulated in S. marcescens by an intercellular communication system termed quorum sensing (QS). Targeting bacterial virulence and QS is an interesting approach to mitigating bacterial pathogenesis and overcoming the development of resistance to antimicrobials. In this study, we aimed to evaluate the anti-virulence activities of secnidazole on a clinical isolate of S. marcescens. The effects of secnidazole at sub-inhibitory concentrations (sub-MICs) on virulence factors, swarming motility, biofilm formation, proteases, hemolysin activity, and prodigiosin production were evaluated in vitro. Secnidazole's protective activity against S. marcescens pathogenesis was assessed in vivo in mice. Furthermore, a molecular docking study was conducted to evaluate the binding ability of secnidazole to the S. marcescens SmaR QS receptor. Our findings showed that secnidazole at sub-MICs significantly reduced S. marcescens virulence factor production in vitro and diminished its pathogenesis in mice. The insilico docking study revealed a great ability of secnidazole to competitively hinder the binding of the autoinducer to the SmaR QS receptor. In conclusion, secnidazole is a promising anti-virulence agent that may be used to control infections caused by S. marcescens.


Initial stages of the contact between a metallic tip and carbon nanotubes.
We present an experimental and theoretical study of the interaction between a tip and single-walled carbon nanotubes (SWCNT) lying on a SiO2 surface. Adhesion and jump-to-contact forces (JC) are measured in a high vacuum system for SWCNT with diameters (D) ranging from 1.4 to 4.5 nm; we find adhesion forces approximately 3.2 nN and JC forces approximately 2.4 nN. Simulations yield adhesion forces in agreement with experiment showing that for D approximately 1.4 nm half of this force is due to tip-SWCNT and tip-SiO2 van der Waals interactions.


Effects of ajmaline on non-sodium ionic currents in guinea pig ventricular myocytes.
The lack of currently available data stimulated us to investigate the electrophysiological effects of ajmaline, a classical class Ia antiarrhythmic agent, on various currents responsible for the action potential plateau and repolarization phases. The whole cell patch clamp recording technique was applied to guinea pig ventricular myocytes. Ajmaline suppressed the Ca2+ current (Ica) in a dose-dependent manner (Kd = 1.2 x 10(-5) M) without affecting the steady-state inactivation kinetics and the voltage dependency of the current-voltage relationship. Ajmaline inhibited the inward portion of the inward rectifying K+ current (IKl). Ajmaline decreased the delayed rectifier K+ current (IK) without altering the activation or deactivation time courses. All these inhibitory effects of ajmaline prolonged the action potential duration in a dose dependent manner. The inhibitory actions of ajmaline on the action potential upstroke and various currents responsible for the plateau and repolarization may contribute to the observed suppression of depolarization-induced abnormal automaticities by this agent.


Filler Content, Surface Microhardness, and Rheological Properties of Various Flowable Resin Composites.
The objectives of this study were to determine the filler content, the surface microhardness (at baseline and after immersion in water for 2 years), and the rheological properties of various flowable resin composites. Three flowable resin composites (Grandioso Heavy Flow [GHF], Grandio Flow [GRF], Filtek Supreme XTE Flow [XTE]), one pit and fissure sealant resin composite (ClinPro [CLI]), and three experimental flowable resin composites with the same matrix and a variable filler content (EXPA, EXPB, EXPC) were tested. The filler content was determined by calcination. The Vickers surface microhardness was determined after polymerization and then after immersion in distilled water at 37°C for 7, 60, 180, 360, and 720 days. The rheological measurements were performed using a dynamic shear rheometer. The determined filler contents differed from the manufacturers' data for all the materials. The materials with the highest filler content presented the highest microhardness, but filler content did not appear to be the only influencing parameter. With respect to the values recorded after photopolymerization, the values were maintained or increased after 720 days compared with the initial microhardness values, except for GHF. For the values measured after immersion for 7 days, an increase in microhardness was observed for all the materials over time. All the materials were non-Newtonian, with shear-thinning behavior. At all the shear speeds, GRF presented a lower viscosity to GHF and XTE. GRF presented a low viscosity before photopolymerization, associated with high filler content, thereby providing a good compromise between spreadability and mechanical properties after photopolymerization.


Nitric oxide involved in the IL-1β-induced inhibition of fructose intestinal transport.
Interleukin-1β (IL-1β) is a pleiotropic cytokine produced by cells of the immune system and a large variety of other cell types including endothelial cells. It is released during inflammatory and infectious diseases, and possesses a wide spectrum of autocrine, paracrine and endocrine activities. The aim of this work was to examine the IL-1β effect on D-fructose transport across rabbit jejunum and try to identify the mediators implicated in this process. A sepsis condition was induced for 90 min after intravenous (iv) administration of IL-1β and body temperature was recorded. Studies on cellular intestinal integrity have not shown modifications of the epithelium and the basement membrane. D-fructose intestinal transport was studied in rabbit jejunum from control and treated animals and it was reduced in the latter ones. This cytokine decreased both the mucosal to serosal transepithelial flux and the transport across brush-border membrane vesicles of D-fructose. The inhibition was reversed by L-NAME (nitric oxide [NO] synthase inhibitor), but not by indomethacin (cyclooxygenase 1 and 2 inhibitor). Both inhibitors were administered iv 15 min before the IL-1β. The protein levels of GLUT5 were not changed in all animal groups and those of mRNA were even increased. In summary, these findings indicate that IL-1β, at the time assayed, induced a significant reduction in the relative intrinsic activity of GLUT5 and in this decrease are involved NO signalling pathways. In this way, blockage of D-fructose intestinal uptake by IL-1β may be playing an essential role in the pathophysiology of septic shock.


Ovarian carcinoma metastasis to the breast case report and review of the literature.
Metastasis to the breast from extramammary malignancies is rare, but its recognition is important because the prognosis and treatment differ from that of primary breast cancer. We report a case of ovarian cancer with metastasis to the breast, which was found at the time of presentation. A 57-year-old woman presented with shortness of breath and was found to have a malignant pleural effusion. A right breast nodule contained papillary adenocarcinoma. Laparotomy showed bilateral ovarian papillary cystadenocarcinoma with dissemination in the peritoneal cavity. DNA image analysis showed multiple aneuploid stem lines. Immunohistochemical staining was positive with ovarian tumor marker OC125 but negative with breast tumor marker gross cystic disease fluid protein-15 (GCDFP-15) and estrogen receptor. The breast specimen was positive with OV632, a more specific tumor marker for ovarian cancer, thus favoring the ovary as the site of the primary tumor.


The usefulness of 3-dimensional virtual simulation using haptics in training orotracheal intubation.
Airway control is the most critical treatment. The most common and basic method of endotracheal intubation is orotracheal intubation. To perform accurate and rapid tracheal intubation, appropriate education and training are required. We developed the virtual simulation program utilizing the 3-dimensional display and haptic device to exercise orotracheal intubation, and the educational effect of this program was compared with that of the mannequin method. The control group used airway mannequin and virtual intubation group was trained with new program. We videotaped both groups during objective structured clinical examination (OSCE) with airway mannequin. The video was reviewed and scored, and the rate of success and time were calculated. The success rate was 78.6% in virtual intubation group and 93.3% in control group (P = 0.273). There was no difference in overall score of OSCE (21.14 ± 4.28 in virtual intubation group and 23.33 ± 4.45 in control group, P = 0.188), the time spent in successful intubation (P = 0.432), and the number of trials (P > 0.101). The virtual simulation with haptics had a similar effect compared with mannequin, but it could be more cost effective and convenient than mannequin training in time and space.


Autocatalytic gene expression occurs via transertion and membrane domain formation and underlies differentiation in bacteria: a model.
When bacteria contain two chromosomes, two or more copies of the same gene are present in the same cytoplasm and, if these copies are subject to negative regulation in trans and positive (autocatalytic) regulation in cis, one copy will be expressed at the expense of the other copy(ies). This autocatalytic process depends on the coupled transcription, or translation and insertion of nascent proteins into the membrane, or transertion. Transertion is responsible for looping genes out of the nucleoid and increasing their accessibility to transcription factors. Transertion of proteins with lipid preferences creates proteolipid domains in the membrane. These domains fuse to give two types of large domains, each associated with the expression of a particular set of genes. These large domains organize kinases, proteases and transcription factors and result in the expression of one set of genes encoding proteins with common lipid preferences from one chromosome and expression of a different set from the other. These intracellular differences underlie the production of different progeny by cell division that follows, for example, reception of extracellular signals, and that constitutes differentiation in bacteria.


Palladium nanoparticles modified electrode for the selective detection of catecholamine neurotransmitters in presence of ascorbic acid.
Palladium (Pd) nanoparticles are directly fabricated on glassy carbon electrode (GCE) and indium tin oxide electrode (ITO) by simple electrochemical deposition process. The Pd nanoparticles modified ITO electrode surface has been studied in detail using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The electrodeposited nano Pd particles are found as spherical shaped in the size range of 39-78 nm. The X-ray diffraction (XRD) analysis reveals that the electrodeposited nano Pd film possesses the face centered cubic crystalline structure. This nano Pd film modified GCE effectively exhibits the electro oxidation signals for the detection of catecholamines epinephrine (EP), norepinephrine (NEP) and dopamine (DA). Especially, the proposed nano Pd film modified GCE successfully showed two well separated anodic oxidation peaks for the detection of catecholamines and ascorbic (AA) in mixture solution. The proposed nano Pd film modified electrode also retains the advantage of easy fabrication, high sensitivity and good repeatability. Finally, this type of nano Pd film modified electrode supports the selective detection of catecholamines in injection solutions.


Changes in Assimilated C Distribution and Soluble Acid Invertase Activity of Zinnia elegans Induced by Uniconazol, an Inhibitor of Gibberellin Biosynthesis.
The physiological aspects involved in the Uniconazol-induced morphological changes in Zinnia elegans Jacq. cv Red Sun were clarified biochemically by determining the distribution of assimilated (13)C as well as the soluble acid invertase activity. The application of Uniconazol, (E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(1,2,4-triazol-1-yl)-1-pentane-3-ol, reduced the growth of stems and leaves without affecting the roots. In addition, the translocation of assimilated (13)C from leaf to other organs was inhibited, with the stem being more restricted than the root. These changes were matched by a corresponding decrease in the specific activity of soluble acid invertase. Subsequent treatment of GA(3) counteracted these effects of Uniconazol. Moreover, the total and reducing sugar content was closely correlated with the soluble acid invertase activity in the stem. It is concluded that the reduction in invertase activity of stem is a biochemical manifestation of the retardation of stem growth induced by Uniconazol.


Diabetic dyslipidaemia.
Diabetic dyslipidaemia is a cluster of plasma lipid and lipoprotein abnormalities that are metabolically interrelated. The increase of large type 1 very low density lipoprotein particles in type 2 diabetes initiates a sequence of events that generates atherogenic remnants, small dense low-density lipoprotein and small dense high-density lipoprotein particles. Thus, it is of great importance to elucidate the mechanisms behind the overproduction of large very low density lipoprotein particles in diabetic dyslipidaemia. This review discusses the pathophysiology of very low density lipoprotein metabolism in type 2 diabetes and recent concepts of lipid management of diabetic dyslipidaemia. Results indicate that triglyceride and apolipoprotein B production in types 1 and 2 very low density lipoprotein are significantly correlated, suggesting a coupling of the two processes governing the metabolism of these lipoprotein subpopulations. Insulin resistance, hyperglycaemia, and liver fat were associated with excess hepatic production of type 1 but not type 2 very low density lipoprotein particles. These data provide support for the independent regulation of types 1 and 2 very low density lipoprotein apolipoprotein B production. Recent data suggest that the assembly of very low density lipoprotein is fundamentally altered in type 2 diabetes, explaining the overproduction of large type 1 very low density lipoprotein as well as the inability of insulin to suppress production of type 1 very low density lipoprotein in type 2 diabetes. Future discoveries hopefully will delineate the regulatory steps to allow more targeted treatment of diabetic dyslipidaemia.


A rare association of tetralogy of Fallot and hypertrophic cardiomyopathy.
Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. It is often associated with other congenital cardiac or non-cardiac defects. However, its association with hypertrophic cardiomyopathy (HCM) is rarely reported. We reported two cases. The first case is a full-term girl receiving modified Blalock-Taussig shunt creation and the second case is an 8-month old boy receiving total correction for TOF. Although they tolerated the operation well, both of them developed congestive heart failure and died of malignant cardiac arrhythmia several months after the operation. We made a literature review and only 11 case reports were found. There is currently no treatment guideline for this group of patients. From our limited experience and case reports, the physiology of HCM and TOF should both be taken into consideration when managing these patients. Close echocardiography follow-up with early myectomy and preventive implantation of implantable cardioverter-defibrillator may be beneficial for them.


Uneven Effects of Sleep Apnea on Semicircular Canals and Otolithic Organs.
This study aimed to explore how obstructive sleep apnea (OSA) affects the function of each vestibular organ and to identify the correlations among them. A prospective study was conducted involving 32 healthy controls and 64 patients with OSA. The objective detection methods of the utricle and saccule are vestibular-evoked myogenic potentials (VEMPs). A combination of the caloric test and video head impulse test (vHIT) was used to comprehensively evaluate the objective function of semicircular canals. Elevated thresholds (p < 0.001), decreased waveform amplitudes (p < 0.001), prolonged first wave latencies (p < 0.001), and shortened first interpeak latencies (p < 0.001) were observed in both ocular VEMP (oVEMP) and cervical VEMP (cVEMP). A significant difference was found in the caloric test comparison (χ2 = 4.030, p = 0.045) but not in the vHIT. The intergroup comparison of normal rates among the VEMPs, caloric test, and vHIT groups showed a significant difference (p < 0.001). The impairment of vestibular function in patients with OSA was uneven and biased. More attention should be given to vestibular dysfunction in the diagnosis and treatment of OSA.


Genotyping Analysis by RAD-Seq Reads Is Useful to Assess the Genetic Identity and Relationships of Breeding Lines in Lavender Species Aimed at Managing Plant Variety Protection.
Lavender species are widely distributed in their wild forms around the Mediterranean Basin and they are also cultivated worldwide as improved and registered clonal varieties. The economic interest of the species belonging to the Lavandula genus is determined by their use as ornamental plants and important source of essential oils that are destinated to the production of cosmetics, pharmaceuticals and foodstuffs. Because of the increasing number of cases of illegal commercialization of selected varieties, the protection of plant breeders' rights has become of main relevance for the recognition of breeding companies' royalties. With this aim, genomic tools based on molecular markers have been demonstrated to be very reliable and transferable among laboratories, and also much more informative than morphological descriptors. With the rising of the next-generation sequencing (NGS) technologies, several genotyping-by-sequencing approaches are now available. This study deals with a deep characterization of 15 varietal clones, belonging to two distinct Lavandula species, by means of restriction-site associated DNA sequencing (RAD-Seq). We demonstrated that this technology screens single nucleotide variants that enable to assess the genetic identity of individual accessions, to reconstruct genetic relationships among related breeding lines, to group them into genetically distinguishable main subclusters, and to assign their molecular lineages to distinct ancestors. Moreover, a number of polymorphic sites were identified within genes putatively involved in biosynthetic pathways related to both tissue pigmentation and terpene production, useful for breeding and/or protecting newly registered varieties. Overall, the results highlighted the presence of pure ancestries and interspecific hybrids for the analyzed Lavandula species, and demonstrated that RAD-Seq analysis is very informative and highly reliable for characterizing Lavandula clones and managing plant variety protection.


How Song Experience Affects Female Mate-Choice, Male Song, and Monoaminergic Activity in the Auditory Telencephalon in Lincoln's Sparrows.
A sexual signal can indicate not only the signaler's attractiveness as a potential mate but also the signaler's competitiveness relative to rivals. As the attractiveness or competitiveness of the prevailing signaling environment increases, individuals prospecting for mates should change their choice threshold, whereas competing individuals should shift resources toward elevating their own competitiveness. Previous studies show that experimental elevations of song competition increase male competitive behavior in Lincoln's sparrows (Melospiza lincolnii) and European starlings (Sturnus vulgaris). Through a series of experimental manipulations using laboratory-housed Lincoln's sparrows, we have also discovered that females change the strength of their song preferences depending on the attractiveness of the song environment to which they have recently been exposed; compared to a less-attractive environment, a highly-attractive environment elevates the threshold for releasing phonotaxis behavior toward male song. These behavioral adjustments are associated with changes in forebrain monoaminergic activity that are triggered by experimental manipulations of the quality of the song environment. Findings from these studies suggest possible neural mechanisms for the regulation of adaptive behavioral plasticity associated with dynamic sexual signaling environments.


Oral health behaviours of older Australian men: the Concord Health and Ageing in Men Project.
The Concord Health and Ageing in Men Project (CHAMP) is a cohort study of the health of a representative sample of older Australian men. The aim of this paper is to describe the oral health behaviours and dental service use of CHAMP participants and explore associations between oral health behaviours with and general health status. Information collected related to socio-demographics, general health, oral health service-use and oral health behaviours. Key general health conditions were ascertained from the health questionnaire and included physical capacity and cognitive status. Fifty-seven percent of the men reported visiting a dental provider at least once or more a year and 56.7% did so for a "dental check-up". Of those with some natural teeth, 59.3% claimed to brush their teeth at least twice or more a day. Most men (96%) used a standard fluoride toothpaste. Few participants used dental floss, tooth picks or mouth-rinses to supplement oral hygiene. Cognitive status and self-rated general health were associated with dental visiting patterns and toothbrushing behaviour. Most older men in CHAMP perform favourable oral health behaviours. Smoking behaviour is associated with less favourable dental visiting patterns, and cognitive status with toothbrushing behaviour.


Mesophyll Resistance and Carboxylase Activity: A Comparison under Water Stress Conditions.
The response of several leaf gas exchange parameters were monitored with decreasing leaf water potential in Phaseolus vulgaris L. leaflets. These included photosynthesis, transpiration, CO(2) compensation point, ribulose 1,5-diphosphate carboxylase activity, boundary layer plus stomatal, and mesophyll resistance to diffusion of CO(2). Mesophyll resistance was calculated under two assumptions: (a) the CO(2) concentration at the chloroplast was zero, and (b) it was equal to the CO(2) compensation point.Contrary to some reports on bean, the estimates of mesophyll resistance (both models) increased with decreasing leaf water potential. Concurrently, the CO(2) compensation point increased and ribulose 1,5-diphosphate carboxylase activity decreased as internal water stress increased.It is suggested that the mesophyll resistance term has been too liberally interpreted in the past and that future use be verified by an indicator of biochemical response to environmental stress such as the assay for ribulose 1,5-diphosphate carboxylase activity.


Cytokinetic effects of bifunctional antitumor intercalator ditercalinium on Friend erythroleukemia cells.
Ditercalinium (NSC 335153) is a novel 7H-pyridocarbazole dimer in which the two monomers are joined by a rigid bis(ethylpiperidinyl)-linking chain producing a molecule capable of bisintercalation into DNA with extremely high affinity. The effect of ditercalinium on cell proliferation and its interaction with DNA in situ has been investigated in the Friend leukemia cell system. Ditercalinium caused an inhibition of cell growth at 0.5 microM and cell death at 2.5 microM. However, both the cytokinetic and cytotoxic effects became evident only after 1-2 days of continuous drug exposure. In contrast, monointercalators generally affect cell growth within several hours of administration. Furthermore, whereas most intercalators arrest cells in G2 phase, ditercalinium demonstrated no cell cycle phase specificity. In fact, a stathmokinetic experiment, in which vinblastine was used to prevent cell division in exponentially growing Friend leukemia cell cultures, demonstrated that ditercalinium effectively "froze" cells in position throughout the cell cycle, in a dose-dependent fashion. By determining the sensitivity of DNA in situ in fixed Friend leukemia cells to acid-induced denaturation, it was apparent that ditercalinium, rather than stabilizing DNA as do monointercalators, increased the sensitivity of DNA in situ to denaturation induced by acid. It appears, therefore, that the cytokinetic effects and interaction with chromatin of an agent that has the ability to bisintercalate into DNA are qualitatively different from those induced by classical monointercalating drugs.


Specific binding of glucose-derivatized polymers to the asialoglycoprotein receptor of mouse primary hepatocytes.
In this study, we designed a novel amphiphilic poly-(p-N-vinylbenzyl-D-glucuronamide) (PV6Gna) modified at the 6-OH position of glucose for hepatocyte recognition to address the mechanism of the interaction between mouse primary hepatocytes and the PV6Gna. PV6Gna bound to lectins specific for glucose but not galactose as did other glucose-derivatized polymers. However, hepatocyte adhesion onto the PV6Gna surface was inhibited in the presence of galactose and its analogues but not in the presence of glucose and its analogues. We also showed that hepatocyte adhesion to the PV6Gna surface was inhibited dose dependently by asialofetuin (ASF). Interactions between soluble PV6Gna and hepatocytes were inhibited by GalNAc, ASF, and EGTA in flow cytometry analysis using fluorescein isothiocyanate-conjugated PV6Gna. Hepatocyte adhesion to the PV6Gna surface was inhibited more effectively by GalNAc than by methyl beta-D-galactose. In flow cytometry analysis and cell adhesion assay, ASF competed for the inhibition of interaction between PV6Gna and hepatocytes 0.5-4 x 10(5)-fold more effectively than did GalNAc. These results demonstrate involvement of asialoglycoprotein receptors (ASGPRs) in the interaction between PV6Gna and hepatocytes. Furthermore, to clarify the mechanism of the interaction between glycopolymers modified at the 6-OH position of glucose and the hepatocyte, we prepared a gel particle containing 6-O-methacryloyl-d-glucose (PMglc) synthesized by an enzymatic method. ASGPRs could be detected using Western blot analysis following precipitation with PMglc in hepatocyte cell lysate. The precipitation of ASGPRs was inhibited in the presence of galactose, ASF, PV6Gna, and EGTA. The precipitation was inhibited more effectively by GalNAc than by methyl beta-d-galactose. ASGPRs were rarely precipitated by PMglc in the cell lysate that had been treated with ASF-conjugated Sepharose. Taken together, we suggest that mouse primary hepatocytes adhere to the PV6Gna surface mediated by ASGPRs, which specifically interacted with the glycopolymers modified at the C-6 position of glucose.


Nuclear transport of nicotinamide phosphoribosyltransferase is cell cycle-dependent in mammalian cells, and its inhibition slows cell growth.
Nicotinamide phosphoribosyltransferase (NAMPT) is located in both the nucleus and cytoplasm and has multiple biological functions including catalyzing the rate-limiting step in NAD synthesis. Moreover, up-regulated NAMPT expression has been observed in many cancers. However, the determinants and regulation of NAMPT's nuclear transport are not known. Here, we constructed a GFP-NAMPT fusion protein to study NAMPT's subcellular trafficking. We observed that in unsynchronized 3T3-L1 preadipocytes, 25% of cells had higher GFP-NAMPT fluorescence in the cytoplasm, and 62% had higher GFP-NAMPT fluorescence in the nucleus. In HepG2 hepatocytes, 6% of cells had higher GFP-NAMPT fluorescence in the cytoplasm, and 84% had higher GFP-NAMPT fluorescence in the nucleus. In both 3T3-L1 and HepG2 cells, GFP-NAMPT was excluded from the nucleus immediately after mitosis and migrated back into it as the cell cycle progressed. In HepG2 cells, endogenous, untagged NAMPT displayed similar changes with the cell cycle, and in nonmitotic cells, GFP-NAMPT accumulated in the nucleus. Similarly, genotoxic, oxidative, or dicarbonyl stress also caused nuclear NAMPT localization. These interventions also increased poly(ADP-ribosyl) polymerase and sirtuin activity, suggesting an increased cellular demand for NAD. We identified a nuclear localization signal in NAMPT and amino acid substitution in this sequence (424RSKK to ASGA), which did not affect its enzymatic activity, blocked nuclear NAMPT transport, slowed cell growth, and increased histone H3 acetylation. These results suggest that NAMPT is transported into the nucleus where it presumably increases NAD synthesis required for cell proliferation. We conclude that specific inhibition of NAMPT transport into the nucleus might be a potential avenue for managing cancer.


The angiotensin II receptor and the actions of angiotensin II.
Angiotensin II (Ang II) is a potent effector peptide of the renin-angiotensin system that exerts a wide variety of physiological actions on the cardiovascular, renal, endocrine, and central and peripheral nervous systems. Angiotensin exerts its actions by binding to specific receptors in the plasma membrane of various tissues. Structure-activity relationship studies and competition-binding experiments have identified a potency series of angiotensin analogues. Such studies have demonstrated that target organs display different preferences for Ang II and homologues such as Ang III and des-[Phe8] angiotensin II. Similarly, agents that normally are considered to be pure receptor antagonists for a given response (tissue) are full agonists in other tissues. Indirect evidence obtained from the above studies have led to the speculation that there are multiple angiotensin receptor subtypes among various tissues as well as within single cell types. Multiple mechanisms of signal transduction have been demonstrated for angiotensin. For example, depending on the effector organ, angiotensin stimulates phosphoinositide turnover and release of internal calcium, modulates voltage-dependent calcium channels, directly activates calcium channels, and inhibits adenylate cyclase activity. Recently, the identification of selective, high-affinity peptide and nonpeptide antagonists has resulted in further characterization of angiotensin receptors into distinct subtypes. In addition, dithiothreitol, an agent that reduces disulfide bridges, has been a useful tool in the characterization of angiotensin receptors as the subtypes apparently are not affected equally by this agent. However, further work needs to be performed to characterize angiotensin receptors with respect to heterogeneity, structure, transducing mechanisms, and physiological function.


The role of persistence in Helicobacter pylori pathogenesis.
Helicobacter pylori induces chronic gastritis and is the strongest known risk factor for peptic ulcer disease and distal gastric cancer, yet only a fraction of colonized individuals ever develop clinical disease. The aim of this article is to provide an overview of recent advances into mechanisms of H. pylori persistence and to incorporate these findings into our current understanding of H. pylori pathogenesis. Recent studies have heightened awareness of the significance of bacterial persistence in H. pylori-associated diseases. Persistence is achieved through initial interactions between H. pylori adhesins and cellular receptors, after which H. pylori must avoid clearance by the immune system. This is accomplished by avoiding host recognition, by producing specific bacterial factors that stimulate selective expression of host genes, and by inducing an ineffective T-cell response. Further, it has become increasingly evident that the genetic diversity of H. pylori also plays a significant role in its persistence. H. pylori persists in its acidic gastric niche, typically for the lifetime of the host. This persistence increases the risk of diseases such as peptic ulcer disease and gastric cancer. Delineation of mechanisms that regulate ongoing H. pylori-host interactions will not only improve targeted diagnostic and therapeutic modalities, but may also provide insights into other diseases that arise within the context of chronic pathogen infection.


Widely tunable chiral nematic liquid crystal optical filter with microsecond switching time.
A wavelength shift of the photonic band gap of 141 nm is obtained by electric switching of a partly polymerized chiral liquid crystal. The devices feature high reflectivity in the photonic band gap without any noticeable degradation or disruption and have response times of 50 µs and 20 µs for switching on and off. The device consists of a mixture of photo-polymerizable liquid crystal, non-reactive nematic liquid crystal and a chiral dopant that has been polymerized with UV light. We investigate the influence of the amplitude of the applied voltage on the width and the depth of the reflection band.


The pseudoradicular syndrome. Lower extremity peripheral nerve entrapment masquerading as lumbar radiculopathy.
Of approximately 4,000 patients with complaints of lower extremity pain who were referred to our center for evaluation of suspected lumbar radiculopathy, 36 were found to have peripheral nerve entrapments as the sole cause of their leg pain. Nine patients had femoral nerve entrapments just proximal to the inguinal ligament. Seven patients had saphenous nerve entrapments about the knee. Twenty patients had peroneal nerve entrapments at or above the popliteal space. Nine patients had tibial nerve entrapments in the popliteal space. The diagnosis was established on the basis of electrophysiologic studies coupled with the results of selective spinal and peripheral nerve blocks. Seven patients with saphenous nerve lesions, 12 patients with peroneal nerve lesions, nine patients with tibial nerve lesions, and four patients with femoral nerve lesions, for a total of 32 (71%) cases underwent surgical exploration and external neurolysis. Forty-four percent of the cases had a positive nerve root tension sign, and 44% (20/45) had spinal range of motion abnormalities. Back pain complaints were noted in 49% (22/45) of the cases. The pseudoradicular syndrome should be considered in cases of undiagnosed persistent leg pain. Peripheral nerve lesions should be ruled out prior to considering lumbar spine surgery.


A New MiRNA MiRm0002 in Eggplant Participates in the Regulation of Defense Responses to Verticillium Wilt.
Verticillium wilt is a major disease that severely affects eggplant production, and a new eggplant miRNA named miRm0002 identified through high-throughput sequencing was highly induced by Verticillium wilt infection. However, the miRm0002 function was still elusive. In this study, the sequence of the miRm0002 precursor was cloned and transgenic eggplants were constructed. In vivo inoculation test and in vitro fungistatic test showed that overexpressing miRm0002 lines were more resistant to Verticillium dahliae and inhibiting miRm0002 lines were more sensitive, compared to the wild-type (WT) control. Some physiological indicators were selected and the results showed that SOD, POD, and CAT activities were significantly increased in Verticillium wilt-infected overexpressing miRm0002 lines, indicating that the expression of miRm0002 activates the antioxidant system. QRT-PCR assay showed that the transcript expression of miRm0002 candidate target ARF8, a gene encoding auxin response factor was negatively related to miRm0002 in WT as well as transgenic eggplants. However, RLM-RACE mapping and degradome sequencing showed miRm0002 could not cleave the sequence of ARF8. Taken together, these data suggest that miRm0002 plays a positive role in the defense response of eggplant against Verticillium wilt.


Effects of a frequent apolipoprotein E isoform, ApoE4Freiburg (Leu28-->Pro), on lipoproteins and the prevalence of coronary artery disease in whites.
Different isoforms of apoE modulate the concentrations of plasma lipoproteins and the risk for atherosclerosis. A novel apoE isoform, apoE4Freiburg, was detected in plasma by isoelectric focusing because its isoelectric point is slightly more acidic than that of apoE4. ApoE4Freiburg results from a base exchange in the APOE4 gene that causes the replacement of a leucine by a proline at position 28. Analysis of the allelic frequencies in whites in southwestern Germany revealed that this isoform is frequent among control subjects (10:4264 alleles) and is even more frequent in patients with coronary artery disease (21:2874 alleles; P=0.004; adjusted odds ratio, 3.09; 95% confidence interval, 1.20 to 7.97). ApoE4Freiburg affects serum lipoproteins by lowering cholesterol, apoB, and apoA-I compared with apoE4 (P<0.05). Our 4 apoE4Freiburg homozygotes suffered from various phenotypes of hyperlipoproteinemia (types IIa, IIb, IV, and V). In vitro binding studies excluded a binding defect of apoE4Freiburg, and in vivo studies excluded an abnormal accumulation of chylomicron remnants. ApoE4Freiburg and apoE4 accumulated to a similar extent in triglyceride-rich lipoproteins. HDLs, however, contained about 40% less apoE4Freiburg than apoE4. In conclusion, our data indicate that apoE4Freiburg exerts its possible atherogenic properties by affecting the metabolism of triglyceride-rich lipoproteins and HDL.


Rh-Catalyzed Reactions of 1,4-Benzoquinones with Electrophiles: C-H Iodination, Bromination, and Phenylselenation.
Under Rh-catalyzed conditions, typically electrophilic 1,4-benzoquinones exhibit nucleophilic reactivity, such that exposure to appropriate electrophiles generates products of C-H iodination, bromination, and phenylselenation. This provides a mild and general method for direct halofunctionalization, and the first method that can achieve direct C-H phenylselenation of this compound class. The scope and limitations of the new protocols are outlined, and representative derivatizations are highlighted.


High Purity Single Wall Carbon Nanotube by Oxygen-Containing Functional Group of Ferrocene-Derived Catalyst Precursor by Floating Catalyst Chemical Vapor Deposition.
Single wall carbon nanotubes (SWCNTs) were synthesized using oxygen-containing ferrocene derived catalysts. The mechanism of synthesizing carbon nanotubes was clarified by the catalyst's exothermic or endothermic decomposition processes. By monitoring the decomposition process of ferrocene-derived catalyst precursors with and without sulfur, we found that the types of oxygen function groups closely influence catalyst formation and nanotube growth. The ferrocene-derived catalyst precursors have a different oxygen containing groups, which are hydroxyl (−OH, ferrocenenemethanol) and carbonyl (C=O, acetylferrocene, and 1,1′-diacetylferrocene). The sulfur chemical state (S 2p) on synthesized catalyst particles using acetylferrocene and 1,1′-diacetylferrocene has more sulfate (SO42−) than others, and there also is a carbon state (C-S-C). The catalyst particle using ferrocenemethanol predominant formed metal−sulfur bonds (such as S2− and Sn2−). The hydroxyl group (−OH) of ferrocenemethanol enhanced the etching effect to remove amorphous carbon and prevented oxidation on the catalyst particle surfaces; however, the carbonyl group (C=O) of acetylferrocene reacted with the catalyst particles to cause partial oxidation and carbon dissociation on the surface of the catalyst particles. The partial oxidation and carbon contamination on catalyst particles controlled the activity of the catalyst. The DFT study revealed that the ferrocene-derived catalyst precursor was dissociated according to following process: the functional groups (such as CH3CO and COH) => first Cp ligands => second Cp ligands. The pyrolysis and release of Fe ions were delayed by the functional groups of ferrocene-derived precursors compared to ferrocene. The thermal-decomposition temperature of the catalyst precursor was high, the decomposition time was be delayed, affecting the formation of catalyst particles and thus making smaller catalyst particles. The size and composition of catalyst particles not only affect the nucleation of CNTs, but also affect physical properties. Therefore, the IG/ID ratio of the CNTs changed from 74 to 18 for acetylferrocene and ferrocene, respectively. The purity also increased from 79 to 90% using ferrocene-derived precursors.


Elements of neural adhesion molecules and a yeast vacuolar protein sorting receptor are present in a novel mammalian low density lipoprotein receptor family member.
Normal cell development depends to a large part on multifunctional proteins that have evolved by recombination of proven modular elements. We now have discovered and characterized in rabbit such a multi-domain protein, and classify it as novel member of the low density lipoprotein (LDL) receptor gene family. The extracellular portion of the approximately 250-kDa membrane protein, termed LR11, contains a cluster of 11 LDL receptor ligand binding repeats, a group of 5 LDL receptor "YWTD" repeats, a large hexarepeat domain of structural elements found in neural cell adhesion molecules, and a domain with similarity to a yeast receptor for vacuolar protein sorting, VPS10. The cytoplasmic domain exhibits features typical of endocytosis-competent coated-pit receptors. The mosaic, and presumably multifunctional, receptor is expressed abundantly in brain, in particular the hippocampus, dentate gyrus, and cerebral cortex, and is present at significant levels in liver, adrenal glands, and testis. Western blotting of tissues and ligand blotting of LR11-transfected cells demonstrated that the novel protein binds apolipoprotein E-containing lipoproteins. In contrast to the LDL receptor, hepatic expression of LR11 is unaffected by hyperlipidemia. The identification of this highly conserved and superbly complex protein offers the opportunity to gain new insights into the emergence of multifunctional mosaic proteins akin to the ever expanding LDL receptor gene family.


Regulation of Bcl-2 oncoprotein levels with differentiation of human neuroblastoma cells.
When established in culture, human neuroblastoma cell lines typically are comprised of heterogeneous cellular subpopulations, including neuroblastic (N-type), substrate-adherent (S-type), and intermediate (I-type) cells that can be distinguished by their characteristic morphologies and expression of differentiation-associated antigens. Here we examined the relative levels of the Bcl-2 oncoprotein in 15 clones derived from four different neuroblastoma cell lines. Among six clones isolated from the SK-N-SH line, levels of p26-Bcl-2 correlated with morphology and differentiation markers with the hierarchy of bcl-2 expression being: N-type cells > N/I-type > I-type > S-type. Furthermore, stimulation of one of the N-type clones, SH-SY5Y, with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, induced differentiation toward a more neuronal-like phenotype and resulted in a 5- to 10-fold elevation in the relative levels of Bcl-2 protein. High relative amounts of p26-Bcl-2 protein were also found in an N-type clone derived from the SMS-KCN line. In two N-type clones derived from the LA-N-1 line, however, levels of Bcl-2 protein were only moderately elevated, and in one N-type clone from the SK-N-BE(2) line the levels of Bcl-2 protein were low. Thus, high relative levels of Bcl-2 oncoprotein are not a universal feature of N-type cells (three of six clones tested). In contrast, all 5 of the S-type clones evaluated contained relatively low levels of Bcl-2 protein, suggesting that these cells (which may represent embryonic precursors of Schwann, glial, and melanocytic cells) do not typically express the bcl-2 gene at high levels. Consistent with this inverse correlation between Bcl-2 protein levels and S-type characteristics, stimulation of an I-type clone derived from the SK-N-BE(2) line with 5-bromodeoxyuridine was accompanied by an accumulation of S-type cells in these cultures, decreased Bcl-2 protein, diminutions in the neuronal markers neurofilament-M and neuron-specific enolase, and an increase in the relative levels of the S-type marker proteins vimentin and beta-2-microglobulin. Conversely, stimulation of this I-type clone with retinoic acid resulted in an accumulation of N-type cells (which are thought to represent embryonic precursors of sympathetic neurons), decreased vimentin and beta-2-microglobulin, increased neurofilament-M, and a marked elevation in p26-Bcl-2.(ABSTRACT TRUNCATED AT 400 WORDS)


Immediate Changes to Skin and Subcutaneous Tissue Strains Following Manual Lymph Drainage in Legs with Lymphedema.
To study the immediate impact of manual lymph drainage (MLD) on skin and subcutaneous tissue strains in legs with lymphedema using free-hand real-time tissue elastography (RTE). Skin and subcutaneous tissue strain measurements were taken at the middle of the inner thigh and calf by RTE in 20 legs with lymphedema of 18 patients (stage II: 11, late stage II: 7, stage III: 2) and in 70 legs of 35 normal subjects. In patients with lymphedema, the same measurements were repeated immediately following MLD. Significant negative correlations were found between pre-MLD strains and the MLD-induced changes in thigh and calf skin strains (thigh skin: p <0.01, calf skin: p = 0.05), but not in subcutaneous tissue strains. Pre-MLD intercepts of these regression lines were closer to normal values as compared to mean pre-MLD values (normal thigh skin: 0.54% ± 0.30%, calf skin: 0.25% ± 0.18%, Pre-MLD thigh skin: 0.39% ± 0.20%, calf skin: 0.17% ± 0.12%, Pre-MLD intercept of thigh skin: 0.48%, Pre-MLD intercept of calf skin: 0.31%). It appears that MLD did not simply soften the skin, but rather normalized it in terms of strain. However, this was not confirmed in the subcutaneous tissue.


Glucose metabolism during resting state reveals abnormal brain networks organization in the Alzheimer's disease and mild cognitive impairment.
This paper aims to study the abnormal patterns of brain glucose metabolism co-variations in Alzheimer disease (AD) and Mild Cognitive Impairment (MCI) patients compared to Normal healthy controls (NC) using the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The local cerebral metabolic rate for glucose (CMRgl) in a set of 90 structures belonging to the AAL atlas was obtained from Fluro-Deoxyglucose Positron Emission Tomography data in resting state. It is assumed that brain regions whose CMRgl values are significantly correlated are functionally associated; therefore, when metabolism is altered in a single region, the alteration will affect the metabolism of other brain areas with which it interrelates. The glucose metabolism network (represented by the matrix of the CMRgl co-variations among all pairs of structures) was studied using the graph theory framework. The highest concurrent fluctuations in CMRgl were basically identified between homologous cortical regions in all groups. Significant differences in CMRgl co-variations in AD and MCI groups as compared to NC were found. The AD and MCI patients showed aberrant patterns in comparison to NC subjects, as detected by global and local network properties (global and local efficiency, clustering index, and others). MCI network's attributes showed an intermediate position between NC and AD, corroborating it as a transitional stage from normal aging to Alzheimer disease. Our study is an attempt at exploring the complex association between glucose metabolism, CMRgl covariations and the attributes of the brain network organization in AD and MCI.


Quantitation of Infliximab and Detection of Antidrug Antibodies in Serum by Use of Surface Plasmon Resonance.
Monitoring infliximab (IFX) concentrations and the presence of antidrug antibodies (ADA) is important for patient management. We developed a method to measure IFX and ADA in serum in a single injection using surface plasmon resonance (SPR). Using the Bio-Rad ProteOn XPR36, tumor necrosis factor-α and IFX were covalently immobilized onto separate lanes of a chip surface. Diluted serum was injected over both lanes, followed by an injection of goat antihuman antibody. The binding response was used to quantify IFX or detect ADA. The analytical performance of the assay was determined. Using 50 patient samples, SPR results were compared with results from a reporter gene assay (RGA). For the quantification of IFX, the functional sensitivity was 0.5 μg/mL. The total precision was <10% for all concentrations tested. IFX concentrations measured by SPR correlated well with RGA (R = 0.862), but a bias was observed (slope = 0.61). SPR detected 14 ADA-positive samples. Compared with RGA for ADA detection, there were 6 true-positive, 8 false-positive, 5 false-negative, and 31 true-negative findings. SPR can be used to measure biological drug concentrations and detect ADA in serum. This technique may provide complementary information to current methods used to detect ADA.


[Pegaptanib sodium one-year treatment study for neovascular age-related macular degeneration].
To evaluate the safety and efficacy of intravitreal administration of pegaptanib sodium in Japanese patients with age-related macular degeneration associated with subfoveal choroidal neovascularization. Ninety-five male and female patients (mean age 72.5 years.) were assigned randomly in a double-masked manner to receive 0.3 or 1 mg of pegaptanib sodium every 6 weeks over a 48-week period. Efficacy was assessed by visual acuity change from baseline as the proportion of patients who lost fewer than 15 letters at week 54 using the Early Treatment Diabetic Retinopathy Study chart. The group that received 0.3 mg pegaptanib experienced a mean loss of 3.8 letters; 78.7% (37/47) of patients lost fewer than 15 letters. The 1 mg group had a change of -4.3 letters and the proportion that lost 15 letters was 72.9% (35/48). The proportion of patients whose visual acuity was unchanged or improved was 46.8% (22/47) and 43.8% (21/48) in the 0.3 and 1 mg groups, respectively. The majority of adverse events with possible, probable, or unknown relationship to pegaptanib were related to the intravitreal injection, such as mild conjunctival hemorrhage (0.3 mg: 76.6%, 1 mg: 77.1%) and superficial punctuate keratitis by sterilization (0.3 mg: 29.8%, 1 mg: 39.6%) at the injection site. Compliance with the study treatment of 9 intravitre al injections was as high as 87.2% and 85.4% for patients receiving 0.3 and 1 mg, respectively. Intravitreal injection of sodium pegaptanib every 6 weeks produced clinically significant stabilization of visual acuity for one year in more than 70% of patients with age-related macular degeneration, with good treatment compliance.


Identification of parasitic nematodes by PCR-SSCP of ITS-2 rDNA.
Fourteen species of parasitic nematodes (order Strongylida) were characterized using a polymerase chain reaction-linked single strand conformation polymorphism technique (PCR-SSCP). The rDNA region spanning the second internal transcribed spacer (ITS-2) was amplified from parasite DNA by PCR. The PCR products were then denatured and subjected to electrophoresis on a non-denaturing gel matrix. PCR-SSCP of the single stranded ITS-2 molecules generated characteristic and reproducible patterns for each species, and allowed the rapid delineation of all of the 14 species in one step. The method also allowed the display of variation in patterns within some species between different geographical isolates. These findings demonstrate the usefulness of PCR-SSCP of ITS-2 for the rapid identification of nematode species and indicate its potential for resolving variation in the ITS-2 sequence within a species.


Aminoguanidine inhibits semicarbazide-sensitive amine oxidase activity: implications for advanced glycation and diabetic complications.
Aminoguanidine, a nucleophilic hydrazine, has been shown to be capable of blocking the formation of advanced glycation end products. It reduces the development of atherosclerotic plaques and prevents experimental diabetic nephropathy. We have found that aminoguanidine is also quite potent at inhibiting semicarbazide-sensitive amine oxidase (SSAO) both in vitro and in vivo. The inhibition is irreversible. This enzyme catalyses the deamination of methylamine and aminoacetone, which leads to the production of cytotoxic formaldehyde and methylglyoxal, respectively. Serum SSAO activity was reported to be increased in diabetic patients and positively correlated with the amount of plasma glycated haemoglobin. Increased SSAO has also been demonstrated in diabetic animal models. Urinary excretion of methylamine is substantially increased in the rats following acute or chronic treatment with aminoguanidine. Urinary methylamine levels were substantially increased in streptozotocin (STZ)-induced diabetic rats following administration of aminoguanidine. The non-hydrazine SSAO inhibitor (E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride (MDL-72974A) has been shown to reduce urinary excretion of lactate dehydrogenase (an indicator of nephropathy) in STZ-induced diabetic rats. Formaldehyde not only induces protein crosslinking, but also enhances the advanced glycation of proteins in vitro. The results support the hypothesis that increased SSAO-mediated deamination may be involved in structural modification of proteins and contribute to advanced glycation in diabetes. The clinical implications for the use of aminoguanidine to prevent glycoxidation have been discussed.


Glucagon/insulin ratio as a potential biomarker for pancreatic cancer in patients with new-onset diabetes mellitus.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with an overall 5-year survival rate of less than 5%. This dismal prognosis is largely due to the advanced stage of the disease at presentation, i.e., the late diagnosis. Therefore, early detection would have the potential to significantly improve the overall prognosis of PDAC patients. Diabetes mellitus (DM) has a high prevalence in PDAC patients and is frequently of new onset. The aim of this study was to analyze whether DM can be utilized as an early disease marker in PDAC. Quantitative RT-PCR analysis and immunohistochemistry for insulin and glucagon was performed in 22 PDAC and 16 normal pancreas tissues. Blood samples of 66 patients suffering from PDAC, 35 DM type 2 patients, and 29 healthy donors were analyzed for insulin, glucagon, C-peptide and glucose levels. Quantitative RT-PCR showed a two-fold increase of the glucagon/insulin ratio in pancreatic cancer tissues in comparison to the normal pancreas. By immunohistochemistry a shift in the expression pattern of glucagon and insulin, i.e., a higher glucagon/insulin ratio was found in PDAC associated islets compared to islets in the normal pancreas. Fasting insulin levels in PDAC patients were lower compared to DM patients. The calculated serum glucagon/insulin ratio was significantly different between PDAC and DM patients. At a cut-off of 7.4 ng/mU glucagon/insulin, pancreatic cancer induced new-onset DM could be discriminated from type 2 DM with 77% sensitivity and 69% specificity. In conclusion, the suggested serum glucagon/insulin ratio showed significant differences in patients with PDAC related DM and type 2 DM. Therefore, this analysis might help to identify PDAC in patients with new-onset DM in the age group at risk. Larger clinical trials have to confirm these findings.


Identification of a biomarker for propetamphos and development of a biological monitoring assay.
This paper describes the identification of a human metabolite of propetamphos ((E-O-2-isopropylcarbonyl-1-methylvinyl-O-methylethylphosphoramidothioate), formed by the hydrolytic cleavage of the enol-vinyl-phosphate bond, and the development of an analytical method suitable for biological monitoring of propetamphos exposure. The metabolite has been detected in the urine of exposed workers but not in that of control subjects. The analytical method involves azeotropic distillation of the urine with acetonitrile, followed by derivatization with pentafluorobenzyl bromide and analysis using gas chromatography with flame photometric detection.


Expression of cold-adapted beta-tubulins confer cold-tolerance to human cellular microtubules.
Isolated microtubule proteins from the cold-adapted fish, Atlantic cod (Gadus morhua), assemble at temperatures between 8 and 30 degrees C, while avian and mammalian microtubules normally do not assemble at temperatures below 20 degrees C. Tubulin, the main component in microtubules, is expressed as many isotypes. Microtubules with different isotype composition have been shown to have different dynamic properties in vitro. Our hypothesis was that cold-tolerance of microtubules is caused by tubulin isotypes that differ in the primary sequence compared to mammalian tubulins. Here we show that transfection of human HepG2 cells with cod beta-tubulin induced cold-adaptation of the endogenous microtubules. Incorporation of one single tubulin isotype can induce cold-tolerance to cold-intolerant microtubules. Three cod beta-tubulin isotypes were tested and two of these (beta1 and beta2) transferred cold-tolerance to HepG2 microtubules, thus not all cod beta-tubulins were able to confer cold-stability.


Mesenteric Lymphatic Alterations Observed During DSS Induced Intestinal Inflammation Are Driven in a TLR4-PAMP/DAMP Discriminative Manner.
Background: Inflammatory bowel disease (IBD) is characterized by both acute and chronic phase inflammation of the gastro-intestinal (GI) tract that affect a large and growing number of people worldwide with little to no effective treatments. This is in part due to the lack of understanding of the disease pathogenesis and also the currently poorly described involvement of other systems such as the lymphatics. During DSS induced colitis, mice also develop a severe inflammation of terminal ileum with many features similar to IBD. As well as inflammation within the ileum we have previously demonstrated lymphatic remodeling within the mesentery and mesenteric lymph nodes of DSS-treated mice. The lymphatic remodeling includes lymphangiogenesis, lymphatic vessel dilation and leakiness, as well as cellular infiltration into the surrounding tissue and peripheral draining lymph nodes. Methods: Intestinal inflammation was induced in C57BL/6 mice by administration of 2.5% DSS in drinking water for 7 days. Mice were treated with TLR4 blocker C34 or Polymyxin-B (PMXB) daily from days 3 to 7 of DSS treatment via I.P. injection, and their therapeutic effects on disease activity and lymphatic function were examined. TLR activity and subsequent effect on lymphangiogenesis, lymphadenopathy, and mesenteric lymph node cellular composition were assessed. Results: DSS Mice treated with TLR4 inhibitor, C34, had a significantly improved disease phenotype characterized by reduced ileal and colonic insult. The change correlated with significant reduction in colonic and mesenteric inflammation, resolved mesenteric lymphangiectasia, and CD103+ DC migration similar to that of healthy control. PMXB treatment however did not resolve inflammation within the colon or associated mesenteric lymphatic dysfunction but did however prevent lymphadenopathy within the MLN through alteration of CCL21 gradients and CD103+ DC migration. Conclusions: TLR4 appears to mediate several changes within the mesenteric lymphatics, more specifically it is shown to have different outcomes whether stimulation occurs through pathogen derived factors such as LPS or tissue derived DAMPs, a novel phenomenon.


Accelerated MR imaging using compressive sensing with no free parameters.
We describe and evaluate a robust method for compressive sensing MRI reconstruction using an iterative soft thresholding framework that is data-driven, so that no tuning of free parameters is required. The approach described here combines a Nesterov type optimal gradient scheme for iterative update along with standard wavelet-based adaptive denoising methods, resulting in a leaner implementation compared with the nonlinear conjugate gradient method. Tests with T₂ weighted brain data and vascular 3D phase contrast data show that the image quality of reconstructions is comparable with those from an empirically tuned nonlinear conjugate gradient approach. Statistical analysis of image quality scores for multiple datasets indicates that the iterative soft thresholding approach as presented here may improve the robustness of the reconstruction and the image quality, when compared with nonlinear conjugate gradient that requires manual tuning for each dataset. A data-driven approach as illustrated in this article should improve future clinical applicability of compressive sensing image reconstruction.


Announcement: National Campaign to Prevent Falls in Construction - United States, May 2-6, 2016.
The National Safety Stand-Down to Prevent Falls in Construction* will be observed May 2-6, 2016, and is hosted by the federal Occupational Safety and Health Administration and stakeholders, including CDC's National Institute for Occupational Safety and Health. During the voluntary stand-down, construction employers are asked to speak directly to their employees about fall hazards to reinforce the importance of adhering to fall prevention measures. Employers are encouraged to have a Spanish speaker deliver the stand-down message to Spanish-speaking employees (simultaneous translation is an alternative). Across the United States, state agencies, public health practitioners, and private contractors will promote participation in the event.


Fatty acid composition of palatal tissue from denture stomatitis patients.
Palatal biopsy specimens were obtained from patients with denture stomatitis. The fatty acids were extracted from the tissue, then separated, identified, and quantified by a gas-chromatographic technique. The sensitivity of this method enabled analyses of specimens with a wet weight of less than 1 mg. The concentration of the fatty acids C16:1 (n-7) and C24:1 (n-9) differed significantly between samples from hyperplastic and clinically healthy tissue in the denture stomatitis patients. By comparing specimens from denture stomatitis patients and non-denture subjects, the concentration of seven fatty acids, two saturated and five unsaturated, was found to be significantly different. A multivariate data-analytical method distinguished between the fatty acid composition in specimens from denture stomatitis patients and from non-denture subjects.


Safety, Pharmacokinetics and Pharmacodynamics of the Selective Glucocorticoid Receptor Modulator Velsecorat (AZD7594) Following Inhalation in Healthy Volunteers.
Velsecorat (AZD7594) is a non-steroidal, selective, glucocorticoid receptor modulator (SGRM), being developed for the treatment of asthma. This article reports the initial, first-in-human, single and repeat dose-escalating study in healthy male volunteers. The study comprised two parts, a single ascending dose part (n=47) and a multiple ascending dose part (n=26). Inhaled velsecorat was administered by nebulization as one single dose in the first part of the study and as a single dose with subsequent multiple daily doses (day 5-16) for 12 days once daily in the second part of the study. At each dose level, participants were randomized to velsecorat (n=6) or placebo (n=2/3). The safety, pharmacokinetics (PK) and pharmacodynamics (PD) of velsecorat were evaluated. Inhaled velsecorat was safe and well tolerated up to and including the highest dose tested (1872 µg). Plasma exposure suggested dose proportional PK. The terminal half-life following repeated dosing was 25-31 hours and steady state conditions for velsecorat in plasma were generally reached within 4 doses. The accumulation ratio was low (≤2), and data did not indicate any time-dependent PK. There were dose-related effects on 24-hour plasma cortisol, plasma cortisol after ACTH stimulation and osteocalcin, systemic PD markers of glucocorticoid activity. There were no effects on other biomarkers tested (DHEA-S and 4βOH-cholesterol). The early clinical evaluation of inhaled velsecorat suggests that this novel SGRM is well tolerated in the dose range investigated. It shows dose proportional plasma exposure, low accumulation, and has dose-dependent effects on markers of glucocorticoid activity.


Pyelovesical bypass graft for palliative management of malignant ureteric obstruction: optimizing the technique by percutaneous access to the bladder using a split Amplatz sheath.
To introduce a simple modification to the original technique of pyelovesical bypass graft placement to make the procedure more minimally invasive. During the study period 2 patients with malignant ureteric obstruction underwent pyelovesical bypass graft placement using Detour stent (Mentor-Porges). The technique simply comprised tract dilatation of the previously placed percutaneous nephrostomy to place the proximal end of the graft in the renal collecting system, making a subcutaneous tunnel from a 1-cm suprapubic incision to the flank area, percutaneous access to the bladder under fluoroscopic guide and placement of the distal end of the stent into the bladder through a split Amplatz sheath. The operative outcome was analyzed prospectively. Both patients tolerated the procedures well with no intra- and postoperative complications. Renal function remained stable during the follow-up period with acceptable urine output through the urethra. Abdominal wall complications such as fistula formation or pain along the subcutaneous tract as well as stent encrustation did not occur during the follow-up period. Despite our small sample size and short follow-up period, percutaneous access to the bladder using a split Amplatz sheath during placement of the Detour stent, may be considered as a promising simple modification to optimize the technique by obviating the need for open cystostomy incision.


Obstructive sleep apnoea, cigarette smoking and plasma orexin-A in a sleep clinic cohort.
Orexin-A is a neuropeptide involved in the regulation of food intake and the sleep-wake cycle. This study investigated plasma orexin-A levels in a sleep clinic cohort, adjusting for smoking habits, in 76 participants comprising 41 with obstructive sleep apnoea (OSA) (apnoea-hypopnoea index [AHI] 44.1 +/- 19.1 events/h) and 35 without OSA (AHI 6.3 +/- 4.7 events/h). Plasma orexin-A levels were significantly lower in OSA patients (15.0 +/- 4.6 ng/ml) compared with those without OSA (31.4 +/- 6.5 ng/ml). In non-OSA subjects, there was no significant difference between never smokers and ex/current smokers in plasma orexin-A levels (32.9 +/- 9.5 versus 29.7 +/- 8.9 ng/ml, respectively) whereas, in the OSA sub-group, orexin-A levels were significantly lower in never smokers than in ex/current smokers (4.0 +/- 1.2 versus 21.4 +/- 7.0 ng/ml). A significant inverse relationship was found between plasma orexin-A levels and AHI amongst never smokers, but there was no significant relationship amongst ex/current smokers. These results confirm previous studies demonstrating lower levels of plasma orexin-A in OSA patients and indicate that smoking may affect orexin-A levels and AHI.


Compliance and treatment satisfaction of post menopausal women treated for osteoporosis. Compliance with osteoporosis treatment.
Adherence to anti-osteoporosis treatments is poor, exposing treated women to increased fracture risk. Determinants of poor adherence are poorly understood. The study aims to determine physician- and patient- rated treatment compliance with osteoporosis treatments and to evaluate factors influencing compliance. This was an observational, cross-sectional pharmacoepidemiological study with a randomly-selected sample of 420 GPs, 154 rheumatologists and 110 gynaecologists practicing in France. Investigators included post-menopausal women with a diagnosis of osteoporosis and a treatment initiated in the previous six months. Investigators completed a questionnaire on clinical features, treatments and medical history, and on patient compliance. Patients completed a questionnaire on sociodemographic features, lifestyle, attitudes and knowledge about osteoporosis, treatment compliance, treatment satisfaction and quality of life. Treatment compliance was evaluated with the Morisky Medication-taking Adherence Scale. Variables collected in the questionnaires were evaluated for association with compliance using multivariate logistic regression analysis. 785 women were evaluated. Physicians considered 95.4% of the sample to be compliant, but only 65.5% of women considered themselves compliant. The correlation between patient and physician perceptions of compliance was low (κ: 0.11 [95% CI: 0.06 to 0.16]). Patient-rated compliance was highest for monthly bisphosphonates (79.7%) and lowest for hormone substitution therapy (50.0%). Six variables were associated with compliance: treatment administration frequency, perceptions of long-term treatment acceptability, perceptions of health consequences of osteoporosis, perceptions of knowledge about osteoporosis, exercise and mental quality of life. Compliance to anti-osteoporosis treatments is poor. Reduction of dosing regimen frequency and patient education may be useful ways of improving compliance.


Coincident Fluorescence-Burst Analysis of the Loading Yields of Exosome-Mimetic Nanovesicles with Fluorescently-Labeled Cargo Molecules.
The possible targeting functionality and low immunogenicity of exosomes and exosome-like nanovesicles make them promising as drug-delivery carriers. To tap into this potential, accurate non-destructive methods to load them and characterize their contents are of utmost importance. However, the small size, polydispersity, and aggregation of nanovesicles in solution make quantitative characterizations of their loading particularly challenging. Here, an ad-hoc methodology is developed based on burst analysis of dual-color confocal fluorescence microscopy experiments, suited for quantitative characterizations of exosome-like nanovesicles and of their fluorescently-labeled loading. It is applied to study exosome-mimetic nanovesicles derived from animal extracellular-vesicles and human red blood cell detergent-resistant membranes, loaded with fluorescently-tagged dUTP cargo molecules. For both classes of nanovesicles, successful loading is proved and by dual-color coincident fluorescence burst analysis, size statistics and loading yields are retrieved and quantified. The procedure affords single-vesicle characterizations well-suited for the investigation of a variety of cargo molecules and biological nanovesicle combinations besides the proof-of-principle demonstrations of this study. The results highlight a powerful characterization tool essential for optimizing the loading process and for advanced engineering of biomimetic nanovesicles for therapeutic drug delivery.


Laser desorption ionisation quadrupole ion trap time-of-flight mass spectrometry of titanium-carbon thin films.
Titanium-carbon (Ti-C) ceramic thin films (abbreviated as n-TiC/a-C:H) are very important for industrial applications. However, their chemical structure is still not completely resolved. The aim of this study was to determine the chemical composition of such n-TiC/a-C:H layers prepared by balanced magnetron sputtering under various experimental conditions. Mass spectrometric analysis of Ti-C thin films was carried out via laser desorption ionisation (LDI) using a quadrupole ion trap and reflectron time-of-flight analyser. The stoichiometry of clusters formed via laser ablation was determined, and the relative abundances of species for which the isotopic patterns overlaps were estimated using a least-squares program. Ti-C films were found to be composites of (i) pure and hydrogenated TiC, (ii) titanium oxycarbides, and (iii) titanium oxides of various degrees of hydrogenation (all embedded in an amorphous and/or diamond-like carbon matrix). Hydrogenated titanium oxycarbide was the main component of the surface layer, whereas deeper layers were composed primarily of TiC and titanium oxides (also embedded in the carbon matrix). Mass spectrometry proved useful for elucidating the chemical structure of the hard ceramic-like Ti-C layers produced by magnetron sputtering. The Ti-C layers were found to be complex composites of various chemical entities. Knowledge of the resolved structure could accelerate further development of these kinds of materials.


Jatrorrhizine: A Review of Sources, Pharmacology, Pharmacokinetics and Toxicity.
Jatrorrhizine, an isoquinoline alkaloid, is a bioactive metabolite in common medicinal plants, such as Berberis vernae Schneid., Tinospora sagittata (Oliv.) Gagnep. and Coptis chinensis Franch. These plants have been used for centuries in traditional medicine for their wide-ranging pharmacological properties. This review emphasizes the latest and comprehensive information on the sources, pharmacology, pharmacokinetics and toxicity of jatrorrhizine. Studies on this alkaloid were collected from scientific internet databases, including the Web of Science, PubMed, ScienceDirect, Google Scholar, Elsevier, Springer, Wiley Online Library and Europe PMC and CNKI, using a combination of keywords involving "jatrorrhizine", "sources", "pharmacology," "pharmacokinetics," and "toxicology". Jatrorrhizine exhibits anti-diabetic, antimicrobial, antiprotozoal, anticancer, anti-obesity and hypolipidemic properties, along with central nervous system activities and other beneficial activity. Studies of jatrorrhizine have laid the foundation for its application to the treatment of various diseases, but some issues still exist. Further investigations might emphasize 1) specific curative mechanisms of jatrorrhizine and clinical utility, 2) application prospect in the treatment of metabolic disorders, 3) comprehensive investigations of the toxicity mechanisms and 4) interactions of jatrorrhizine with other pharmaceuticals and development of derivatives.


Febrile seizures.
Febrile seizure (FS) is the most common seizure disorder of childhood, and occurs in an age-related manner. FS are classified into simple and complex. FS has a multifactorial inheritance, suggesting that both genetic and environmental factors are causative. Various animal models have elucidated the pathophysiological mechanisms of FS. Risk factors for a first FS are a family history of the disorder and a developmental delay. Risk factors for recurrent FS are a family history, age below 18 months at seizure onset, maximum temperature, and duration of fever. Risk factors for subsequent development of epilepsy are neurodevelopmental abnormality and complex FS. Clinicians evaluating children after a simple FS should concentrate on identifying the cause of the child's fever. Meningitis should be considered in the differential diagnosis for any febrile child. A simple FS does not usually require further evaluation such as ordering electroencephalography, neuroimaging, or other studies. Treatment is acute rescue therapy for prolonged FS. Antipyretics are not proven to reduce the recurrence risk for FS. Some evidence shows that both intermittent therapy with oral/rectal diazepam and continuous prophylaxis with oral phenobarbital or valproate are effective in reducing the risk of recurrence, but there is no evidence that these medications reduce the risk of subsequent epilepsy. Vaccine-induced FS is a rare event that does not lead to deleterious outcomes, but could affect patient and physician attitudes toward the safety of vaccination.


Potato responds to salt stress by increased activity of antioxidant enzymes.
To understand the response of potato to salt stress, antioxidant enzyme activities and ion content were analyzed for a sensitive and a tolerant cultivar. Nodal cuttings of the tolerant cultivar, Kennebec, and the sensitive cultivar, Concord, were exposed to media without or with 30, 60, 90 or 120 mmol/L NaCl for 4 weeks. On exposure to NaCl, the length and fresh and dry weight of both shoots and roots of Concord showed greater decrease than those of Kennebec. The decrease in shoot growth was more severe than that of the root for both cultivars. The K(+) content of shoots and roots of both cultivars was reduced in a dose-dependent manner by exposure to NaCl; the Na(+) content increased. Activities of ascorbate peroxidase, catalase and glutathione reductase were increased in NaCl-exposed shoots of Kennebec; the corresponding activities in NaCl-exposed shoots of Concord were decreased. Roots of both cultivars showed similar changes in the activities of these enzymes on exposure to NaCl. These studies established that enzyme activities in Concord shoots are inversely related to the NaCl concentration, whereas those in Kennebec do not show a dose dependency, which is also the case for the roots of both cultivars. Our findings suggest that an increase in activity of antioxidant enzymes, such as ascorbate peroxidase, catalase and glutathione reductase, can contribute to salt tolerance in Kennebec, a salt resistant cultivar of potato.


Masseter-to-Facial Nerve Transfer for Reanimation of a Patient With Long-Term Facial Paralysis.
Facial paralysis is a condition caused by a wide variety of etiologies, including neurologic, congenital, infectious, neoplastic, systemic, and iatrogenic causes. A patient suffering from long-term facial paralysis, with minimal innervation detected through electroneurography, who was successfully reanimated by performing a masseter-to-facial nerve transfer, was presented in this study. Facial paralysis had been caused after resection of an acquired middle ear cholesteatoma more than 5 years before.