Endovascular versus medical therapy for uncomplicated type B aortic dissection: a qualitative review.
Uncomplicated type B dissections have been traditionally managed with antihypertensive therapy. In the endovascular era, this dictum has been revisited. This review pooled the available studies to compare the outcomes of best medical therapy (BMT) to thoracic endovascular aortic repair (TEVAR) for uncomplicated type B dissections. A literature search was performed to identify studies on uncomplicated type B dissections managed with BMT with and without TEVAR. The primary outcome measures were mortality rates at 30 days and at 2 years following intervention. A total of 6 studies included 123 patients who underwent TEVAR/BMT, and 566 patients who had BMT alone. The mortality rates at 30 days (6.5% TEVAR/BMT vs 4.8% BMT, P = .21) and at 2 years (9.7% vs 11.9%, P = .32) were similar. Renal failure was greater in TEVAR/BMT (15.4% vs 2.1%, P < .01). Rates of surgical reintervention/intervention were similar (17.6% vs 20.1%, P = .31). The TEVAR with BMT does not provide survival benefit compared to BMT alone, 2 years following uncomplicated type B aortic dissection.


Investing in the comeback: parent's experience following traumatic brain injury.
The increasing incidence of survival following traumatic brain injury necessitates a closer examination of long-term care and caregiver issues. A sample of parents and brain-injured offspring from 20 families was explored to identify a qualitatively-generated theory describing the parent's experience following a brain-injured child's return to the home setting. The grounded theory methodology was used during data collection and analysis. All the brain-injured offspring had survived moderate to severe traumatic brain injury, were living with at least one parent, and were aged 17-34 years. Investing in the Comeback is the generated three-phase theory. These three phases--centering on, fostering independence and seeking stability describe the work of parents living with brain-injured offspring.


γ-Aminobutyric acid (GABA) regulates lipid production and cadmium uptake by Monoraphidium sp. QLY-1 under cadmium stress.
This study explored the effects of γ-aminobutyric acid (GABA) on the production of biomass and lipids and on the uptake of Cd2+ by microalgae under cadmium (Cd) stress. Compared with the control and Cd stress alone, 2.5 mM GABA increased the maximum lipid content (55.37%) by 49.37% and 9.42%, respectively. GABA application resulted in increased contents of protein and glutathione (GSH) and in upregulated activity of α-amylase but decreased contents of starch, reactive oxygen species (ROS) and Cd2+, with no effect on subsequent biodiesel quality. Additional analysis of GABA further indicated that increased cellular GABA contents could promote lipid synthesis and reduce Cd accumulation by regulating the expression levels of lipogenesis genes, ROS signalling and mineral nutrient uptake under Cd stress. Collectively, these findings show that GABA not only increases lipid production in microalgae but also is involved in the mechanisms by which microalgae respond to Cd stress.


Manipulation of visual information affects control strategy during a visuomotor tracking task.
Proper understanding of motor control requires insight into the extent and manner in which task performance and control strategy are influenced by various aspects of visual information. We therefore systematically manipulated the visual presentation (i.e., scaling factor and optical flow density) of a visuomotor tracking task without changing the task itself, and investigated the effect on performance, effort, motor control strategy (i.e., anticipatory or corrective steering) and underlying neuromechanical parameters (i.e., intrinsic muscle stiffness and damping, and proprioceptive and visual feedback). Twenty healthy participants controlled the left-right position of a virtual car (by means of wrist rotations in a haptic robot) to track a slightly curved virtual road (presented on a 60" LED screen), while small torque perturbations were applied to the wrist (1.25-20Hz multisine) for quantification of the neuromechanical parameters. This visuomotor tracking task was performed in conditions with low/medium/high scaling factor and low/high optical flow density. Task performance was high in all conditions (tracking accuracy 96.6%-100%); a higher scaling factor was associated with slightly better performance. As expected, participants did adapt their control strategy and the use of proprioceptive and visual feedback in response to changes in the visual presentation. These findings indicate that effects of visual representation on motor behavior should be taken into consideration in designing, interpreting and comparing experiments on motor control in health and disease. In future studies, these insights might be exploited to assess the sensory-motor adaptability in various clinical conditions.


Do working conditions explain the increased risks of disability pension among men and women with low education? A follow-up of Swedish cohorts.
Rates of disability pension are greatly increased among people with low education. This study examines the extent to which associations between education and disability pensions might be explained by differences in working conditions. Information on individuals at age 13 years was used to assess confounding of associations. Two nationally representative samples of men and women born in 1948 and 1953 in Sweden (22 889 participants in total) were linked to information from social insurance records on cause (musculoskeletal, psychiatric, and other) and date (from 1986-2008) of disability pension. Education data were obtained from administrative records. Occupation data were used for measurement of physical strain at work and job control. Data on paternal education, ambition to study, and intellectual performance were collected in school. Women were found to have higher rates of disability pension than men, regardless of diagnosis, whereas men had a steeper increase in disability pension by declining educational level. Adjustment of associations for paternal education, ambition to study, and intellectual performance at age 13 had a considerable attenuating effect, also when disability pension with a musculoskeletal diagnosis was the outcome. Despite this, high physical strain at work and low job control both contributed to explain the associations between low education and disability pensions in multivariable models. Working conditions seem to partly explain the increased rate of disability pension among men and women with lower education even though this association does reflect considerable selection effects based on factors already present in late childhood.


Fluorescence studies of Hoechst 33342 with supercoiled and relaxed plasmid pBR322 DNA.
The fluorescence properties of Hoechst 33342 (HO 33342) were examined with plasmid pBR322 in the supercoiled (Form I) or relaxed covalently closed circular (Form Io) conformation in order to determine whether qualitative or quantitative differences in fluorescence properties might provide an assay for topological states of DNA. It was found that HO 33342 exhibited a 30% greater fluorescence intensity with Form I pBR322, independent of the dye or DNA concentration. As the dye to DNA ratio was increased, a red shift of approximately 8 nm was observed for HO 33342 complexed with Form I or Form Io. The red shift in fluorescence emission occurred at higher HO 33342 concentrations with Form I vs. Form Io DNA; however, when Form I and Form Io were mixed in various proportions, neither the fluorescent intensity differences nor the HO 33342 concentration at which the wavelength shift occurred could be used to quantitate the relative proportions of topological states present. These results suggest that although the fluorescence properties of HO 33342 complexed with Form I DNA are different than those of HO 33342 complexed with Form Io DNA, the fluorescence assay is not sufficiently sensitive to quantitatively discriminate among a mixture of DNA in various topological states.


The role of standards in creating a health information infrastructure.
In the belief that the existence of a variety of standards is an absolute necessity for health care professional workstations to work, this paper provides a detailed overview of the standards efforts of a number of groups. According to the International Standards Organization (ISO) Reference Model, workstations require a full level of standards from the physical level through and beyond the applications level. Rapidly changing technology challenges acceptance of standards at the lower levels. Current recommendations include fiberoptic media using certain protocols. Other standards in these lower levels also have support. At the applications level, data messaging standards are being developed by six groups. The consensus standards body for the United States is coordinating the efforts of these groups in order to produce a harmonized effort, and is coordinating the effort with Europe for an international effort. Work on the development of the full set of standards necessary for workstation implementations is lagging. Accelerating the process is mandatory if we are to achieve the necessary seamless interoperability required by workstations for ubiquitous intelligent communications between the workstations and the sources of data.


Cost functions and model combination for VaR-based asset allocation using neural networks.
We introduce an asset-allocation framework based on the active control of the value-at-risk of the portfolio. Within this framework, we compare two paradigms for making the allocation using neural networks. The first one uses the network to make a forecast of asset behavior, in conjunction with a traditional mean-variance allocator for constructing the portfolio. The second paradigm uses the network to directly make the portfolio allocation decisions. We consider a method for performing soft input variable selection, and show its considerable utility. We use model combination (committee) methods to systematize the choice of hyperparameters during training. We show that committees using both paradigms are significantly outperforming the benchmark market performance.


[Relationships between masticatory performance and nutritional state in complete denture wearers].
For many authors masticatory dysfunctions are related to reduction in dietary intake with malnutrition as a possible consequence. The aim of the present study was to further investigate the relationships between masticatory performance and nutritional state in complete denture wearers. Masticatory performance was assessed using a granulometric method in 74 subjects divided into 2 subgroups according to their dental status (normal dentition and complete dental wearers). Nutritional status of study subjects was analyzed with Mini Nutritional Assessment (MNA). There were a significant association between wearing denture and Nutritional Status as assessed by MNA. Using this scale, a risk of malnutrition was found in 80% of subjects wearing complete denture and in 26% in the normal dentition sub group (p < 0.0001). There were also a positive and significant correlation between, the particle size distribution and masticated test food and nutritional status. Complete denture wearers are at greater risk of malnutrition than did subjects with normal dentition.


Sphingosine 1-phosphate Receptor 2 Signaling Suppresses Macrophage Phagocytosis and Impairs Host Defense against Sepsis.
Sepsis is characterized by an inappropriate systemic inflammatory response and bacteremia that promote multiorgan failure and mortality. Sphingosine 1-phosphate receptor 2 (S1PR2) modulates endotoxin-induced inflammation in endothelium. However, as a highly expressed S1P receptor in macrophages, its role in regulating macrophage response to bacterial infection remains unclear. Cecal ligation and puncture or intratracheal instillation of Escherichia coli was induced in wild-type or S1pr2-deficient mice. The antibacterial ability of cell-specific S1PR2 was tested in bone marrow reconstitution mice or mice with macrophage-specific deletion. Signaling molecules responsible for S1PR2-mediated phagocytosis were also measured in the bone marrow-derived macrophages. In addition, S1PR2 expression levels and its correlation with severity of sepsis were determined in critically ill patients (n = 25). Both genetic deletion and pharmaceutical inhibition of S1PR2 significantly limited bacterial burden, reduced lung damage, and improved survival (genetic deletion, 0% in S1pr2 vs. 78.6% in S1pr2, P < 0.001; pharmaceutical inhibition, 9.1% in vehicle vs. 22.2% in S1PR2 antagonist, P < 0.05). This protection was attributed to the enhanced phagocytic function of S1PR2-deficient macrophages (mean fluorescent intensity, 2035.2 ± 202.1 vs. 407.8 ± 71.6, P < 0.001). Absence of S1PR2 in macrophage inhibits RhoA-dependent cell contraction and promotes IQGAP1-Rac1-dependent lamellipodial protrusion, whose signaling pathways depend on extracellular stimulators. In septic patients, increased S1PR2 levels in peripheral blood mononuclear cells were positively correlated with the severity of sepsis (r = 0.845, P < 0.001). This study implies that S1PR2, as a critical receptor in macrophage, impairs phagocytosis and antimicrobial defense in the pathogenesis of sepsis. Interventions targeting S1PR2 signaling may serve as promising therapeutic approaches for sepsis.


Optical Absorption Spectra Calculated from a First-Principles Wave Function Theory for Solids: Transcorrelated Method Combined with Configuration Interaction Singles.
We present a new ab initio method for excited-state calculations based on wave function theory: transcorrelated (TC) method combined with configuration interaction singles (CIS). Conventional CIS with the Hartree-Fock wave function, while a popular method for excited-state calculations of molecular systems, cannot describe electron correlation effects, such as the screening effect in solids, resulting in inaccurate results such as overestimation of the band gap and exciton binding energy. Here, we adopt the TC method, which takes electron correlations into account through a similarity transformation of the Hamiltonian using the Jastrow factor, and combine it with the CIS approximation. We calculate the optical absorption spectra of solid LiF and GaAs as a test, and verify that the present method reproduces the spectra more accurately than the conventional HF-CIS. The excitonic effect is well described with our method.


Regulation of insulin-like growth factor I receptor expression by the pure antiestrogen ICI 182780.
Insulin-like growth factor I (IGF-I) is a mitogen for human breast cancer cells both in vivo and in vitro. We demonstrate here that the antiestrogen ICI 182780 (ICI) at 10(-8) m decreases IGF-I receptor (IGF-IR) mRNA levels by 70% after treatment for 48 h. Measurements of mRNA stability indicate that the half-life of IGF-IR mRNA is approximately 3 h. Estradiol treatment increases the half-life of the IGF-IR mRNA to approximately 6 h and the level of IGF-IR gene transcription by 1.8-fold, whereas ICI treatment not only decreases the IGF-IR transcription rate by 50% but also decreases the IGF-IR mRNA half-life to less than 3 h. Affinity labeling studies with [125I]-IGF-I show 35% increased labeled IGF-I to MCF-7 cell membrane following estradiol treatment and 40% decreased labeling following ICI treatment. We also demonstrate that ICI attenuates IGF-I-stimulated growth. Our data suggest that attenuation of IGF-I responsivity by ICI may be due in part to reducing the IGF-IR expression.


The effect of heat and radiation on the initiation and elongation processes of DNA synthesis.
The pH step alkaline elution and alkaline sucrose gradient techniques were utilized to evaluate alterations in DNA replication (initiation and elongation) induced by heat and low dose X-irradiation is synchronized Chinese hamster ovary cells. The initiation and elongation process of DNA synthesis were radioresistant at the G1/S boundary (4 hours after mitosis) while in mid S phase (9 hours after mitosis) DNA initiation and elongation were sensitive to X-irradiation. The initiation and elongation processes of DNA synthesis which were radiation resistant at the G1/S boundary could be inhibited by a hyperthermia treatment (43 degrees C for 1 hour beginning at 4 hours after mitosis). The impairment of initiation in the heated cells was maintained through late S phase while that of elongation was reversible as judged by full recovery at 15 hours after mitosis. These data suggest that the known synergistic lethality of heat and radiation may be mediated by an impairment of initiation of DNA synthesis.


[Modification of pediatric lung function measurement by antibacterial filters].
The risk of cross-infection by contaminated lung function equipment can be reduced by the use of antibacterial filters. These filters, however, should have no significant influence on flow measurements. We investigated the effect of a new filter (Pall PF 30) on lung function measurements in 92 children and adolescents with bronchial asthma and cystic fibrosis. In randomized sequence, flow-volume curves and spirometry were registered in the whole body plethysmograph. Values measured with filter correlated closely to those registered without; individual values remained close to the line of identity. With high flow rates, however, there was a minimal tendency towards lower measurements with filter; this damping effect was flow-dependent and remained of a clinically insignificant dimension.


Comparing two methods of topical anesthesia used before intravenous cannulation in pediatric patients.
The purpose of this study was to compare the efficacy of two methods of topical anesthesia before venipuncture or intravenous cannulation of pediatric patients to assess which type of topical anesthetic would better alleviate pain in the least amount of time with the greatest success rate of cannulation. This study was a randomly controlled trial of 100 preoperative pediatric patients aged 5 to 21 years. The following methods of topical anesthesia were compared: (a) iontophoresis of a topical solution of 2% lidocaine with epinephrine 1:100,000 using a Phoresor Dose Controller (PDC) with Numby Stuff electrodes and a eutectic mixture of local anesthetic and (b) 2.5% lidocaine and 2.5% prilocaine (eutectic mixture of local anesthetics [EMLA] cream). Children reported less pain with iontophoresis (M = 0.08) compared with EMLA cream (M = 1.88, P < .001). Time to accomplish topical anesthesia was shorter with iontophoresis (13 minutes) compared with EMLA cream (60 minutes, P < .001). Failure to accomplish venipuncture occurred 5 times with the iontophoresis method and 8 times with the EMLA method (not significant). No dermal burns resulted from use of iontophoresis. We conclude that use of iontophoresis in pediatric patients is safe, rapid, and significantly more effective than is EMLA cream in reducing pain associated with venipuncture or intravenous cannulation.


Role of the second disulfide bridge (Cys(18)-Cys(274)) in stabilizing the inactive AT₁ receptor.
Previous research showed that disruption of the Cys(18)-Cys(274) bond in the angiotensin II (AngII) AT₁ receptor mutant (C18S), expressed in CHO cells, causes an increase in the basal activity and attenuation of the maximum response to AngII. In addition, this mutant was mostly intracellularly distributed. Our aim was to investigate whether the intracellular presence of the mutant was due to a constitutive internalization or to a defective maturation of the receptor. The first hypothesis was assessed by pretreating the cells with losartan or [Sar¹Leu⁸]-AngII, specific AT₁ receptor antagonists, a maneuver to revert the receptor internalization. The second hypothesis was tested using calnexin, an endoplasmic reticulum marker. We found that treatment with AT₁ receptor antagonists causes an increase in the binding ability of the mutant to AngII. Furthermore, whereas the maximum effect is increased, it reduces the enhanced basal levels of IP₃. The hypothesis for a lack of maturation of the mutant receptor was ruled out because calnexin was poorly colocalized with the intracellular C18S receptor. Our results suggest that the mutation of the AT₁ receptor leads to a conformational structure similar to that of the active mode of the AT₁ receptor, favoring its internalization in the absence of the agonist.


Synthesis and characterization of new bifunctional nanocomposites possessing upconversion and oxygen-sensing properties.
A new type of bifunctional nanocomposites for biomedical applications, upconversion NaY F(4):Y b(3+), Tm(3+) nanoparticles coated with Ru(II) complex chemically doped SiO(2), has been developed by combining the useful functions of upconversion and oxygen-sensing properties into one nanoparticle. NaY F(4):Y b(3+), Tm(3+) nanoparticles were successfully coated with an Ru(II) complex doped SiO(2) shell with a thickness of approximately 30 nm, and the surface of the SiO(2) was functionalized with amines. The obtained nanocomposites exhibited bright blue upconversion emission, and the luminescent emission intensity of the Ru(II) complex in the nanocomposites was sensitive to oxygen. Compared with the simple mixture of Ru(II) complex and SiO(2), the core-shell nanocomposites showed better linearity between emission intensity of Ru(II) complex and oxygen concentrations. These bifunctional nanocomposites may find applications in biochemical and biomedical fields, such as biolabels and optical oxygen sensors, which can measure the oxygen concentrations in biological fluids.


[MELATONIN TREATMENT OF AUTOIMMUNE AND ALLERGIC PATHOLOGY].
Some autoimmune and allergic diseases (systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, atopic dermatitis, etc.) are accompanied with disturbances of the natural production of hormone melatonin by pineal gland and peripheral tissues. The administration of melatonin to animals and humans with such pathologies demonstrated showed a protective effect. It is proposed to carry out additional investigations of the possibility of using melatonin for the treatment of autoimmune disorders, after which it can be introduced into clinical practice.


Resolving the role of plant glutamate dehydrogenase: II. Physiological characterization of plants overexpressing the two enzyme subunits individually or simultaneously.
Glutamate dehydrogenase (GDH; EC 1.4.1.2) is able to carry out the deamination of glutamate in higher plants. In order to obtain a better understanding of the physiological function of GDH in leaves, transgenic tobacco (Nicotiana tabacum L.) plants were constructed that overexpress two genes from Nicotiana plumbaginifolia (GDHA and GDHB under the control of the Cauliflower mosiac virus 35S promoter), which encode the α- and β-subunits of GDH individually or simultaneously. In the transgenic plants, the GDH protein accumulated in the mitochondria of mesophyll cells and in the mitochondria of the phloem companion cells (CCs), where the native enzyme is normally expressed. Such a shift in the cellular location of the GDH enzyme induced major changes in carbon and nitrogen metabolite accumulation and a reduction in growth. These changes were mainly characterized by a decrease in the amount of sucrose, starch and glutamine in the leaves, which was accompanied by an increase in the amount of nitrate and Chl. In addition, there was an increase in the content of asparagine and a decrease in proline. Such changes may explain the lower plant biomass determined in the GDH-overexpressing lines. Overexpressing the two genes GDHA and GDHB individually or simultaneously induced a differential accumulation of glutamate and glutamine and a modification of the glutamate to glutamine ratio. The impact of the metabolic changes occurring in the different types of GDH-overexpressing plants is discussed in relation to the possible physiological function of each subunit when present in the form of homohexamers or heterohexamers.


Tricyclic antidepressants: plasma levels and clinical findings in overdose.
Following amitriptyline or imipramine overdose by 30 patients, total plasma concentrations ranged from 29 to 1732 ng/ml but did not correlate well with physical findings or most electrocardiographic changes. Only those patients with a QRS interval greater than 0.1 second had significantly elevated plasma levels. However, a plasma level ratio of the parent drug (amitriptyline, imipramine) to its respective N-desmethyl metabolite (nortriptyline, desmethylimipramine) greater than or equal to 2.0 was associated with an acute overdose. This ratio was more useful than total plasma levels in differentiating an overdose from a therapeutic dose with associated toxicity and an elevated steady-state plasma level.


WITHDRAWN: Dissolution enhancement of indomethacin by inclusion into porous silica: 3-D ordered macroporous silica versus 2-D ordered mesoporous silica.
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


[Comprehensive treatment in Achilles tendon rupture].
Due to incapacity caused by calcaneal tendon injuries for the reintegration of patients back to their daily activities and/or sparts it is necessary to decrease the time of reinstatement of patients. At present these times have improved by a good surgical technique and an early rehabilitation, and the patient is returned quickly as he sees less disability. It is proposed in this paper a type of surgical treatment and an early rehabilitation program, which have shortened the time of disability and incorporation to their daily activities and sports to eight weeks in 10 patients with Achilles tendon plasty.


Heritability, family, school and academic achievement in adolescence.
We demonstrate how genetically informed designs can be applied to administrative exam data to study academic achievement. ACE mixture latent class models have been used with Year 6 and 9 exam data for seven cohorts of Polish students which include 24,285 pairs of twins. Depending on a learning domain and classroom environment history, from 58% to 88% of variance in exam results is attributable to heritability, up to 34% to shared environment and from 8% to 15% depends on unique events in students' lives. Moreover, between 54% and 66% of variance in students' learning gains made between Years 6 and 9 is explained by heritability. The unique environment accounts for between 34% and 46% of that variance. However, we find no classroom effects on student progress made between Years 6 and 9. We situate this finding against the view that classroom peer groups and teachers matter for adolescent learning.


Postpartum bleeding.
The nurse caring for the postpartum woman must be able to distinguish normal from abnormal blood loss. Characteristics that identify normal lochia are reviewed, as are important nursing assessment parameters. Guidelines for managing impending shock are provided. Problems with blood volume estimations are explored. Information on resumption of menses and patient teaching approaches related to late postpartum hemorrhage are included.


Chemically enhanced phytoextraction of Pb by wheat in texturally different soils.
A pot study was used to examine the effects of amendments such as EDTA and elemental sulfur on the growth potential, gas exchange features, uptake and mobilization of Pb by wheat (Triticum aestivum L.) in two texturally different contaminated soils at three levels of EDTA (2, 4, 8 mmol kg(-1) dry soil) and two levels of elemental sulfur (100, 200 mmol kg(-1) dry soil). EDTA resulted in more solubilization of Pb than elemental sulfur in both soils. Application of EDTA and elemental sulfur increased shoot dry matter in the loamy sand soil, whereas in the sandy clay loam soil EDTA treated plants produced lower shoot dry matter compared to that observed with elemental sulfur. Application of EDTA 10d prior to harvest increased the amount of Pb accumulated into wheat shoots with more Pb accumulated by plants from the loamy sand than from the sandy clay loam soil. However, evaluation of the relative extraction efficiency expressed as the percentage of solubilized Pb that is subsequently also effectively accumulated by the plant shoots reveals that the relatively low efficiency does not warrant the massive mobilization induced by the environmentally persistent EDTA chelator. More modest mobilization of Pb induced by elemental sulfur and the higher relative extraction of mobilized Pb therefore deserves further attention in future research. In particular, attention needs to be paid to determining soil types in which elemental sulfur can induce significant impact on soil pH and metal mobility after application of a practically realistic dosage.


The role of polypeptide growth factors in human carcinomas: new targets for a novel pharmacological approach.
The processes of cellular proliferation and progressive acquisition of a specialized phenotype show a high degree of coordination. In particular, these complex signaling networks mediating cell growth, differentiation, migration, and apoptosis are regulated in part by polypeptide growth factors that can act, by autocrine and/or paracrine mechanisms of action, as positive or negative modulators. Because these growth factors are unable to cross the hydrophobic cell membrane, they exert their effects via binding to cell surface receptors, most of which possess intrinsic tyrosine kinase activity. Owing to the interaction of polypeptide growth factors with their specific transmembrane receptors, a cascade of intracellular biochemical signals, resulting in the activation and repression of various subsets of genes, is triggered. One of the major incentives for studying factors that regulate processes of proliferation and differentiation is the recognition of their involvement in tumorigenesis. Genetic aberrations in growth factors signaling pathways are, in fact, inextricably linked to cancer. Malignant cells arise as a result of a stepwise progression of genetic events characterized by the unregulated expression of growth factors or components of their signaling networks. The main aim of this review is to examine the current understanding of the crucial contribution that several growth factors may have on transformation, tumorigenesis, and progression in several human tumors among the most widespread in western countries. For this purpose, we will analyze the chemistry and the molecular organization of the most important growth factors and their specific receptors. In addition, we will focus on the mechanisms of signal transduction, the complex cascade of biochemical events ensued from the growth factor/receptor binding. The present knowledge of the role of growth factor biochemical signaling networks in cancer leads to improvements not only in diagnosis and prognosis for this disease, but also for new and more targeted therapeutic intervention. The second part of this review will focus on the novel pharmacological approaches for cancer therapy that have been developed already or are being developed with the aim to specifically interfere at various steps of the growth factors signaling pathways.


Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within a secondary care setting.
The diagnosis of dementia relies on the presence of new-onset cognitive impairment affecting an individual's functioning and activities of daily living. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) is a questionnaire instrument, completed by a suitable 'informant' who knows the patient well, designed to assess change in functional performance secondary to cognitive change; it is used as a tool to identifying those who may have dementia.In secondary care there are two specific instances where patients may be assessed for the presence of dementia. These are in the general acute hospital setting, where opportunistic screening may be undertaken, or in specialist memory services where individuals have been referred due to perceived cognitive problems. To ensure an instrument is suitable for diagnostic use in these settings, its test accuracy must be established. To determine the diagnostic accuracy of the informant-based questionnaire IQCODE, for detection of all-cause (undifferentiated) dementia in adults presenting to secondary-care services. We searched the following sources on the 28th of January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (Ovid SP), EMBASE (Ovid SP), PsycINFO (Ovid SP), BIOSIS Previews (Thomson Reuters Web of Science), Web of Science Core Collection (includes Conference Proceedings Citation Index) (Thomson Reuters Web of Science), CINAHL (EBSCOhost) and LILACS (BIREME). We also searched sources specific to diagnostic test accuracy: MEDION (Universities of Maastricht and Leuven); DARE (Database of Abstracts of Reviews of Effects - via the Cochrane Library); HTA Database (Health Technology Assessment Database via the Cochrane Library) and ARIF (Birmingham University). We also checked reference lists of relevant studies and reviews, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on IQCODE for dementia diagnosis to try to find additional studies. We developed a sensitive search strategy; search terms were designed to cover key concepts using several different approaches run in parallel and included terms relating to cognitive tests, cognitive screening and dementia. We used standardised database subject headings such as MeSH terms (in MEDLINE) and other standardised headings (controlled vocabulary) in other databases, as appropriate. We selected those studies performed in secondary-care settings, which included (not necessarily exclusively) IQCODE to assess for the presence of dementia and where dementia diagnosis was confirmed with clinical assessment. For the 'secondary care' setting we included all studies which assessed patients in hospital (e.g. acute unscheduled admissions, referrals to specialist geriatric assessment services etc.) and those referred for specialist 'memory' assessment, typically in psychogeriatric services. We screened all titles generated by electronic database searches, and reviewed abstracts of all potentially relevant studies. Two independent assessors checked full papers for eligibility and extracted data. We determined quality assessment (risk of bias and applicability) using the QUADAS-2 tool, and reporting quality using the STARD tool. From 72 papers describing IQCODE test accuracy, we included 13 papers, representing data from 2745 individuals (n = 1413 (51%) with dementia). Pooled analysis of all studies using data presented closest to a cut-off of 3.3 indicated that sensitivity was 0.91 (95% CI 0.86 to 0.94); specificity 0.66 (95% CI 0.56 to 0.75); the positive likelihood ratio was 2.7 (95% CI 2.0 to 3.6) and the negative likelihood ratio was 0.14 (95% CI 0.09 to 0.22).There was a statistically significant difference in test accuracy between the general hospital setting and the specialist memory setting (P = 0.019), suggesting that IQCODE performs better in a 'general' setting.We found no significant differences in the test accuracy of the short (16-item) versus the 26-item IQCODE, or in the language of administration.There was significant heterogeneity in the included studies, including a highly varied prevalence of dementia (10.5% to 87.4%). Across the included papers there was substantial potential for bias, particularly around sampling of included participants and selection criteria, which may limit generalisability. There was also evidence of suboptimal reporting, particularly around disease severity and handling indeterminate results, which are important if considering use in clinical practice. The IQCODE can be used to identify older adults in the general hospital setting who are at risk of dementia and require specialist assessment; it is useful specifically for ruling out those without evidence of cognitive decline. The language of administration did not affect test accuracy, which supports the cross-cultural use of the tool. These findings are qualified by the significant heterogeneity, the potential for bias and suboptimal reporting found in the included studies.


Pituitary apoplexy occurring during large volume liposuction surgery.
A 50-year-old woman developed headache and right-sided ophthalmoplegia upon awakening from general anesthesia after liposuction surgery on her abdomen, hips, and thighs. Neuroimaging showed hemorrhage within a previously undiagnosed pituitary adenoma. The confirmatory surgical specimen contained areas of gross infarction and hemorrhage. The anesthesia record revealed intraoperative reduction of systolic blood pressure to 90 mm Hg for 30 minutes from a baseline of 120 mm Hg. This first reported case of pituitary apoplexy during liposuction surgery probably resulted from intraoperative hypotension attributed to a combination of general anesthesia, the use of subcutaneous lidocaine, sequestration of plasma in injured tissues, and blood loss.


Spectrophotometric study on the reactions of iron(II) and iron(III) with Bromopyrogallol Red and hexadecyltrimethylammonium bromide.
Bromopyrogallol Red (BPR) combines with iron(III) in the presence of hexadecyltrimethylammonium bromide (CTMAB) to form an intensely blue complex having a molar absorptivity of 5.20 x 10(4)l. mole(-1).cm(-1) at 635 nm. The complex contains three molecules of BPR co-ordinated to an iron(III) ion, and two molecules of CTMAB associated with each BPR molecule, giving the overall formula (CTMAB)(6)(BPR)(3)Fe(III). Iron(II) also reacts with BPR and CTMAB in the presence of dissolved oxygen to form the iron(III) complex. No oxidizing or reducing agents are required for the determination of total iron in mixtures of iron(III) and iron(II), and Beer's law is followed from 0.05 to 0.5 ppm iron (1.00-cm cells). Of nine metal ions tested at the 1-ppm level, only manganese(II) and vanadium(V) interfere. Copper(II), cobalt(II), zinc, lead, nickel, aluminium and chromium(III) produce little or no interference when present at 100 ppm concentration.


Alpha4beta1 and alpha5beta1 control cell migration on fibronectin by differentially regulating cell speed and motile cell phenotype.
Computer-aided time lapse fluorescence videomicroscopy was used to study single cell migration behavior of human aortic endothelial cells on fibronectin coated substrates of varying protein surface density. The role of receptors alpha5beta1, alpha(v)beta3, and alpha4beta1 in mediating cell adhesion and migration on fibronectin was characterized using integrin specific monoclonal antibodies. Matrix density had a direct effect on controlling the proportion of migrating cells and the directional persistence of cell movement (p<0.01). While there was relatively little influence of fibronectin surface density on absolute migration speed, the ability of endothelial cells to disperse over a surface, as measured by the dispersion coefficient, was biphasic with respect to the surface density of this matrix protein (p<0.005). Both cell speed and the proportion of migrating cells was controlled by alpha4beta1 (p<0.01). However, alpha5beta1 selectively regulated the transformation of stationary cells to those exhibiting motile behavior (p<0.05). Migratory responses on fibronectin were not influenced by blockade of the alpha(v)beta3 receptor. It is noteworthy that cell surface adhesive receptors which control commitment to a motile phenotype are not necessarily the same as those that control migration speed.


Organ donation after cardiac death: donor and recipient outcomes after the first three years of the Ontario experience.
The aim of this study was to explore donor and recipient outcomes from organ donation after cardiac death (DCD) in Ontario and to examine the impact of DCD on deceased donation rates in Ontario since its implementation. Donor data were obtained from the Trillium Gift of Life Network (TGLN) TOTAL database from June 1, 2006 until May 31, 2009. All DCDs were tracked, including unsuccessful DCD attempts during that time. For the first 36 months after DCD implementation, all Ontario solid organ transplant programs that utilized organs from DCD provided clinical outcome data at one year. Total DCD activity until December 1, 2010 was also tracked. In addition, we compared organ donation and DCD rates across all Canadian jurisdictions and the USA. For the first 36 months of DCD activity in Ontario, June 1, 2006 to May 31, 2009, there were 67 successful DCDs out of 87 attempted DCDs in 18 Ontario hospitals, resulting in 128 kidney, 41 liver, and 21 lung transplants. The one-year kidney patient and death-censored allograft survivals were 96 and 97%, respectively. Mean (SD) creatinine at 12 months was 150 (108) μmol·L(-1). In 26 (20%) extended criteria donors (ECD-DCD), the one-year creatinine was 206 (158) μmol·L(-1) vs 137 (80) μmol·L(-1) in 102 standard criteria donors (SCD-DCD) (P = 0.002). The one-year liver and lung allograft survivals were 78% and 70%, respectively. Since its implementation four and a half years ago, DCD has accounted for 10.9% of deceased donor activity in Ontario. In 2009, Ontario had a record number of organ donors. Of the 221 deceased donors, 37 (17%) donors were DCD. By December 1, 2010 there were 121 DCD Ontario donors resulting in > 300 solid organ transplants and accounting for 90% of all DCD activity in the country. The rapid update of DCD in Ontario can be attributed to strong proponents in the critical care and transplantation communities with continued support from Trillium Gift of Life Network (TGLN). Ontario is the only province to demonstrate growth in deceased donor rates over the last decade (25% over the last four years), which can be attributed primarily to the success of its DCD activity.


Association of Common Carotid Artery Measurements with N-terminal Pro B-type Natriuretic Peptide in Elderly Participants.
Objective Numerous studies have reported an association between common carotid artery (CCA) parameters and atherosclerotic cardiovascular disease (CVD). However, the association between CCA parameters and hemodynamic stress on the left ventricle in elderly patients remains unclear. Methods We assessed CCA parameters, including the height-adjusted CCA interadventitial diameter (diameter/height), mean intima-media thickness (IMT), number of plaques, plaque score, resistance index (RI), and pulsatility index (PI) with ultrasonography, using serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels as a marker for hemodynamic stress on the left ventricle in 1,315 participants ≥70 years old without CVD. Of these participants, 706 had hypertension, defined as taking antihypertensive medications, having a systolic blood pressure ≥140 mmHg, and/or having a diastolic blood pressure ≥90 mmHg. Results After adjusting for the confounding factors, the CCA interadventitial diameter/height was significantly associated with the log NT-proBNP in both the normotensive group (β=0.125, p=0.002) and hypertensive group (β=0.080, p=0.029). The RI was significantly associated with the log NT-proBNP in the hypertensive group (β=0.176, p<0.001) but not in the normotensive group. In addition, the PI was significantly associated with the log NT-proBNP in the hypertensive group (β=0.156, p<0.001) but not in the normotensive group. However, no significant association was observed between the mean IMT, number of plaques, and plaque score and log NT-proBNP. Conclusion CCA measurements may be useful markers for hemodynamic stress on the left ventricle in elderly patients.


Metabolic syndrome is an important factor for the evolution of prognosis of colorectal cancer: survival, recurrence, and liver metastasis.
Several studies have shown that metabolic syndrome (MS) was a risk factor for colorectal cancer, but few studies have reported the relationship between MS and the prognosis of colorectal cancer. Data were collected from 507 cases of colorectal carcinoma between January 2002 and March 2007 to establish the database. These patients were divided into 2 groups based on the presence of MS. We tested the prognostic value of MS in the patients. The risk of adverse events was examined by Cox proportional hazard modeling. The rates of liver metastasis and tumor recurrence were higher in the group of patients with colorectal cancer accompanied by MS. Moreover, MS is one of the important elements that independently can influence the survival (colonic carcinoma: hazard ratio [HR], 1.633; 95% confidence interval [CI], 1.039-2.565; rectal carcinoma: HR, 1.939, 95% CI, 1.076-3.494) and liver metastasis (colonic carcinoma: HR, 2.619; 95% CI, 1.288-5.324; rectal carcinoma: HR, 2.814; 95% CI, .962-2.888) of both colonic and rectal carcinoma patients, and MS patients have the highest risk with worse survival and liver metastases compared with other parameters. The results suggest that MS may be an important prognostic factor for colorectal cancer, decreasing the incidence of MS may improve the therapeutic efficacy of colorectal cancer.


Preemptive kidney transplant from deceased donors: an advantage in relation to reduced waiting list.
Preemptive living donor kidney transplantation is associated with better allograft and recipient survival. However, it remains unclear whether preemptive transplantation from deceased donors is beneficial too. An increased number of deceased donors has reduced the waiting list in our hospital in the last years allowing preemptive deceased donor kidney transplantation (PDDKT). We compared our experience with preemptive transplantation with patients who underwent dialysis before transplantation. Thirty-three PDDKT, including 77.5% male patients of overall mean age of 48 +/- 14 years, were performed in our hospital between January 1999 and December 2004 (8% of transplantations). We compared the outcomes of these patients with those of renal transplants in subjects who had undergone dialysis. The donors for both groups had similar characteristic; they were paired donor kidneys in most cases. The types of donors in both groups were: non-heart-beating (49%), heart-beating deceased (27%) or en bloc pediatric (24%). The serum creatinine of the recipients was 6.9 +/- 1.8 mg/dL prior to transplantation, and the creatinine clearance was 14.6 +/- 3.6 mL/min (estimated by the Cockroft-Gault formula). The Charlson comorbidity index adapted for patients with advanced chronic kidney disease (ACKD) was 0.8 +/- 0.2 in the preemptive group versus 1.7 +/- 0.4 in the dialysis group (P < .05). Delayed graft function rates were 0% versus 25% in preemptive vs dialysis groups, respectively. No differences in 1-month or 1-year renal function as determined by serum creatinine were observed between the groups. We did not observe differences in the incidence of acute rejection or 1- and 2-year graft and patient survivals. PDDKT is the treatment of choice for ACKD. It is associated with less delayed graft function and similar 2-year graft and patient survivals than kidney transplantation after dialysis. The Charlson index reflected less comorbidity among patients with PDDKT, a finding that must influence long-term outcomes.


Dying of a broken heart: ethics and law in a case of hypoplastic left heart syndrome.
The short life of Baby P is reviewed. Baby P was an infant girl who was born with hypoplastic left heart syndrome and died at the age of 30 days. Effective, aggressive surgical treatment for this condition is rapidly developing in some countries, but is rarely available or successful in most. Baby P died without intervention. After presenting the history and background, the legal and ethical issues raised by this case regarding decision-making, futility, and best interests are reviewed.


[Late complications after alloplastic vascular replacement].
The follow-up of 273 AAA patients operated 1981-1985 showed a mean dilation of polyester grafts of 17.4% in 12 days and 34.8% in 3 years. This early dilation is due to mesh expansion of the warp knitted grafts. It has no clinical relevance. In contrary the late dilation after approximately 10 years is due to degradation. The evaluation of 436 explanted grafts attained from 75 hospitals showed graft rupture to be the cause of the explanation for 42/255 (16%) polyester grafts and 2/42 (5%) PTFE grafts. The most ruptures were observed in the surrounding of the inguinal ligament after 10 to 20 years of duration. In comparison to modern endovascular grafts the conventional polyester and PTFE grafts still are the gold standard of durability.


Looking and search measures of object knowledge in preschool children.
The same preschoolers were tested on an observation task and a search task involving the invisible displacement of an object. In the observation task, children watched an object roll behind a screen from which protruded the top of a solid wall. Analyses revealed significantly longer looking to impossible than to possible outcomes in all children. In search, the child was allowed to retrieve the rolled object. Most 3-year-olds but significantly fewer 2.5-year-olds completed the search successfully. An unexpected sex difference was found, with boys outperforming girls. Search performance was not associated with observation measures. The findings indicate that children visually discriminate violations of solidity but that this sensitivity is not associated with successful search performance.


(1)H NMR Spectroscopy of Fecal Extracts Enables Detection of Advanced Colorectal Neoplasia.
Colorectal cancer (CRC) is a growing cause of mortality in developing countries, warranting investigation into its etiopathogenesis and earlier diagnosis. Here, we investigated the fecal metabolic phenotype of patients with advanced colorectal neoplasia and controls using (1)H-nuclear magnetic resonance (NMR) spectroscopy and multivariate modeling. The fecal microbiota composition was assessed by quantitative real-time PCR as well as Wif-1 methylation levels in stools, serum, and urine and correlated to the metabolic profile of each patient. The predictivity of the model was 0.507 (Q(2)Y), and the explained variance was 0.755 (R(2)Y). Patients with advanced colorectal neoplasia demonstrated increased fecal concentrations of four short-chain fatty acids (valerate, acetate, propionate, and butyrate) and decreased signals relating to β-glucose, glutamine, and glutamate. The predictive accuracy of the multivariate (1)H NMR model was higher than that of the guaiac-fecal occult blood test and the Wif-1 methylation test for predicting advanced colorectal neoplasia. Correlation analysis between fecal metabolites and bacterial profiles revealed strong associations between Faecalibacterium prausnitzii and Clostridium leptum species with short-chain fatty acids concentration and inverse correlation between Faecalibacterium prausnitzii and glucose. These preliminary results suggest that fecal metabonomics may potentially have a future role in a noninvasive colorectal screening program and may contribute to our understanding of the role of these dysregulated molecules in the cross-talk between the host and its bacterial microbiota.


[Role of a surveillance system developed by the Viareggio Local Health Unit in injury prevention].
Statistics on occupational injuries published by INVAIL (National Insurance Institute for Occupational Accidents and Diseases) are not useful to plan appropriate preventive actions in local manufacturing sectors. The injury surveillance system, developed by Viareggio Local Health Unit, collects data on all occupational injuries that occurred in the Versilia area, by enterprise, worksite and manufacturing sector. Enterprises operating in particular sectors (e.g. shipyards, construction) are classified differently than in the national injury surveillance system. After trend analysis and interpretation of injury data, the main results are available both in electronic and paper format. Surveillance data are used by the Local Health Unit to promote and formulate specific preventive actions, such as: research and development of safer tools, promotion and control of safer use of specific tools, promotion and enforcement of good practices, control programmes in high risk manufacturing sectors and jobs.


Consequences of ionizing radiation-induced damage in human neural stem cells.
Cranial irradiation remains a frontline treatment for brain cancer, but also leads to normal tissue damage. Although low-dose irradiation (≤10 Gy) causes minimal histopathologic change, it can elicit variable degrees of cognitive dysfunction that are associated with the depletion of neural stem cells. To decipher the mechanisms underlying radiation-induced stem cell dysfunction, human neural stem cells (hNSCs) subjected to clinically relevant irradiation (0-5 Gy) were analyzed for survival parameters, cell-cycle alterations, DNA damage and repair, and oxidative stress. hNSCs showed a marked sensitivity to low-dose irradiation that was in part due to elevated apoptosis and the inhibition of cell-cycle progression that manifested as a G2/M checkpoint delay. Efficient removal of DNA double-strand breaks was indicated by the disappearance of γ-H2AX nuclear foci. A dose-responsive and persistent increase in oxidative and nitrosative stress was found in irradiated hNSCs, possibly the result of a higher metabolic activity in the fraction of surviving cells. These data highlight the marked sensitivity of hNSCs to low-dose irradiation and suggest that long-lasting perturbations in the CNS microenvironment due to radiation-induced oxidative stress can compromise the functionality of neural stem cells.


Photocatalytic reactivities of Nafion-coated TiO2 for the degradation of charged organic compounds under UV or visible light.
Nafion (perfluorinated polymer with sulfonate groups)-coated TiO2 particles (Nf/TiO2) were prepared and their reactivities for the photocatalytic degradation (PCD) of charged organic substrates were investigated. The presence of Nafion adlayers drastically changed the positive TiO2 surface charge to a negative one over the entire pH range and significantly influenced the PCD kinetics and mechanisms. The UV-induced PCD of tetramethylammonium (TMA; cationic substrate) was greatly enhanced in the presence of Nafion adlayers on TiO2 because the ion-exchange sites within the Nafion can hold cationic substrates. On the other hand, despite the unfavorable electrostatic interaction between the Nf/TiO2 and anionic substrates, the PCD of dichloroacetate (DCA) and acid orange 7 (AO7) with Nf/TiO2 was not significantly inhibited. The visible-light-sensitized degradation of dyes was enhanced with Nf/TiO2 not only for cationic dyes (methylene blue (MB) and rhodamine B (RhB)) whose uptake on Nf/TiO2 is enhanced, but also for an anionic dye (AO7) that is less adsorbed on Nf/TiO2. The unexpected behavior in AO7 degradation seems to be related to the role of the Nafion layer in retarding the charge recombination. These observations indicate that Nf/TiO2 can enhance the PCD reactivity for cationic substrates without sacrificing the PCD reactivity for anionic substrates. In addition, it was found that the sensitized degradation of RhB followed a different path when the surface of TiO2 was coated with Nafion. The N-de-ethylation of RhB that leads to the generation of rhodamine-110 was a prevailing path with Nf/TiO2, whereas the cleavage of the chromophoric ring structure was dominant with pure TiO2. The effects of Nafion adlayers on the photoinduced electron transfer and PCD kinetics and mechanisms are discussed.


Anti-inflammatory and protective effects of MT-031, a novel multitarget MAO-A and AChE/BuChE inhibitor in scopolamine mouse model and inflammatory cells.
Previous study demonstrated that the novel multitarget compound, MT-031 preserved in one molecule entity the beneficial properties of its parent drugs, rasagiline and rivastigmine, and exerted high dual potencies of monoamine oxidase-A (MAO-A) and cholinesterase (ChE) inhibition in acute-treated mice and neuroprotective effects against H2O2-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. The present study aimed to further investigate the anti-inflammatory and protective effects of MT-031 in scopolamine mouse model and inflammatory cell cultures. Our findings demonstrated that once daily chronic administration of MT-031 (5-10 mg/kg) to mice antagonized scopolamine-induced memory and cognitive impairments, displayed brain selective MAO-A and AChE/BuChE inhibition, increased the levels of striatal dopamine (DA), serotonin (5-HT) and norepinephrine and prevented the metabolism of DA and 5-HT. In addition, MT-031 upregulated mRNA expression levels of Bcl-2, the neurotrophic factors, (e.g., brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF)), the antioxidant enzyme catalase and the anti-inflammatory cytokine, neurotrophic tyrosine kinase receptor (Ntrk), and down-regulated the mRNA expression levels of the pro-inflammatory interleukin (IL)-6 in scopolamine-induced mice. In accordance, MT-031 was shown to reduce reactive oxygen species accumulation, increase the levels of anti-inflammatory cytokines, IL-10 and decrease the levels of the pro-inflammatory cytokines, IL-1β, IL-6, IL-17 and interferon-gamma (IFN-γ) in activated mouse splenocytes and microglial cells. Taken together, these pharmacological properties of MT-031 can be of clinical importance for developing this novel multitarget compound as a novel drug candidate for the treatment of Alzheimer's disease.


Paragonimiasis: an infrequent but treatable cause of hemoptysis in systemic lupus erythematosus.
Hemoptysis in systemic lupus erythematosus (SLE) may occur in up to 17% of cases. The vast majority of the cases are secondary to bacterial, tuberculosis or opportunistic infections. Also uremia, pulmonary embolism and lung hemorrhage must be considered. The majority of the above referred entities are usually alarming events in any patient with SLE. In contrast, we describe a patient with inactive SLE, who developed hemoptysis secondary to Paragonimus sp., which was treated "easily" with praziquantel. Fluke infection must be considered in the differential diagnosis of hemoptysis in SLE.


RNA splicing. U2 fulfils a commitment.
Genetic and biochemical studies of pre-mRNA splicing have recently converged to elucidate an early step in the process: the targeting of the U2 small nuclear ribonucleoprotein particle to the pre-mRNA.


Assessing the influence of altitude and temperature on biological monitoring of freshwater quality: A preliminary investigation.
The effect of altitude and water temperature on biomonitoring of freshwater quality was examined along an unpolluted area (36 km in length) of the upper Río Tajo (central Spain). The macrobenthic and fish communities were studied, and the Biological Monitoring Water Quality (BMWQ) method was applied. As expected, values of altitude and temperature respectively decreased and increased with increasing distance from the river source; these two physical parameters exhibited a negative and significant (P<0.05) correlation coefficient between them. However, despite evident changes in the functional structure of both aquatic communities along the study area, BMWQ scores were similar at all sampling sites. Pearson correlation coefficients between physical and biological parameters were not significant (P>0.05). The BMWQ index only exhibited significant (positive) correlation coefficients with macrobenthic and fish biomasses, indicating that freshwater quality could affect the biological production of fluvial ecosystems. It is concluded that biomonitoring of freshwater quality may be independent of the influence of altitude and water temperature at local spatial scales. Nonetheless, further investigations would be needed to clearly differentiate between the effects of anthropogenic and natural causes on biological monitoring at larger spatial scales.


Association of dietary cholesterol and egg intakes with the risk of incident dementia or Alzheimer disease: the Kuopio Ischaemic Heart Disease Risk Factor Study.
There is little information about the associations of intakes of cholesterol and eggs, a major source of dietary cholesterol, with the risk of cognitive decline in general populations or in carriers of apolipoprotein E ɛ4 (APO-E4), a major risk factor for dementia. We investigated the associations of cholesterol and egg intakes with incident dementia, Alzheimer disease (AD), and cognitive performance in middle-aged and older men from Eastern Finland. A total of 2497 dementia-free men, aged 42-60 y in 1984-1989 at the baseline examinations of the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study, were included in the study. Information on the apolipoprotein E (Apo-E) phenotype was available for 1259 men. Data on cognitive performance tests at the 4-y re-examinations were available for 480 men. Dietary intakes were assessed with the use of 4-d food records at baseline. Dementia and AD diagnoses were based on Finnish health registers. Cox regression and ANCOVA were used for the analyses. During the 21.9-y follow-up, 337 men were diagnosed with dementia, and 266 men were diagnosed with AD. Neither cholesterol nor egg intake was associated with a higher risk of incident dementia or AD. For example, when evaluated continuously, each intake of 100 mg cholesterol/d was associated with a multivariable-adjusted HR of 0.90 (95% CI: 0.79, 1.02) for incident dementia, and each additional 0.5 egg (27 g)/d was associated with an HR of 0.89 (95% CI: 0.78, 1.01). However, egg intake was associated with better performance on neuropsychological tests of the frontal lobe and executive functioning, the Trail Making Test, and the Verbal Fluency Test. The Apo-E4 phenotype did not modify the associations of cholesterol or egg intake (P-interactions > 0.11). Neither cholesterol nor egg intake is associated with an increased risk of incident dementia or AD in Eastern Finnish men. Instead, moderate egg intake may have a beneficial association with certain areas of cognitive performance.


Value of low-dose 2 x 2 Gy palliative radiotherapy in advanced low-grade non-Hodgkin's lymphoma.
Low-dose radiotherapy over the last decade has been reported to provide effective palliation for patients with low-grade non-Hodgkin's lymphoma. In this retrospective case series of 10 patients, we report our early experience using low-dose radiotherapy (usually 2 x 2 Gy) for patients with advanced-stage follicular, mucosal associated lymphoid tissue, mantle cell and small lymphocytic lymphomas. Median follow up was 27 weeks. Response rates were high (complete response, 70%; partial response, 20%), the response durable and the toxicity was minimal (no toxicity greater than grade 1). Low-dose irradiation is an effective treatment option for patients with low-grade lymphomas with local symptoms.


Association between the occurrence of the anticardiolipin IgM and mite allergen-specific IgE antibodies in children with extrinsic type of atopic eczema/dermatitis syndrome.
As the literature has only controversial data on the role of nonallergen-specific antibodies in atopic eczema dermatitis syndrome, the authors investigated the link between the occurrence of the antiphospholipid [anticardiolipin (ACL), anti-beta2-glycoprotein I] and allergen-specific immunoglobulin E (IgE) antibodies in 72 children with atopic eczema/dermatitis syndrome (AEDS). The measurement of antiphospholipid antibodies was carried out by enzyme-linked immunosorbent assay (ELISA), serum total IgE by nephelometry, and allergen-specific IgE by immunoblotting assay. The statistical analysis was carried out by Fisher's exact test and odds ratio was calculated. Thirteen of 72 children with AEDS (mean age 8.3 years) had elevated serum levels of ACL, and eight anti-beta2-glycoprotein I antibodies. The presence of allergen-specific IgE against inhalant allergens and nutritive allergens was among eight of 13 and three of eight in the cases with elevated ACL. The ratio of patients with highly increased severity scoring of atopic dermatitis (SCORAD) index (>75) was significantly higher in the group with elevated (4/13) than in those with the normal ACL levels (2/59). There was a significant association between the appearance of mite (Dermatophagoides pteronyssinus, D. farinae)-specific IgE and ACL IgM antibodies (6/13). These findings show that there are significant linkage and association between the appearance of ACL IgM or the production of allergen-specific IgE against inhalant (mainly mite) allergens in children with atopic eczema/dermatitis syndrome.


Clinical and immunologic features of selective IgA deficiency.
Selective absence of serum and secretory IgA is probably the most common form of human immunodeficiency. High frequencies of recurrent sinusitis, otitis media, pneumonia, and atopy were noted among a group of 75 such patients, all but 4 of whom were Caucasian. Seven instances of familial absence of IgA were detected among 106 relatives of 34 of the group; in 1 family 1 member from each of 3 successive generations was affected. Two IgA-deficient children were later found to have normal amounts of serum IgA. Despite their humoral deficit, B lymphocytes bearing surface IgA were detected in 9/9 IgA-deficient patients in immunofluorescence studies of their peripheral blood lymphocytes. Although in vitro lymphocyte responses to 2 putative T-cell mitogens and to allogenic cells were normal, results of spontaneous rosette formation studies with sheep erythrocytes raise the possibility of a lymphocyte subpopulation deficit in this condition.


Altered expression profile of superoxide dismutase isoforms in nasal polyps from nonallergic patients.
Nasal polyposis (NP) is a chronic inflammatory disease of the upper respiratory tract. The pathophysiology is unknown but has been shown to be multifactorial. Free radical-mediated damage has been implicated in the pathogenesis of NP. Superoxide dismutases (SODs) are the first and the most important line of antioxidant enzyme defense against reactive oxygen species. Moreover, isozymes of the SOD family are critical for modulating the activity of nitric oxide, a gaseous free radical that is believed to play roles in the physiology and pathology of respiratory tracts. However, the expression profile of SOD isoforms in NP remains unclear. We aimed to investigate the expression profile of the SOD isoforms in nasal polyps from nonallergic patients. Prospective study. Nasal polyp tissues were obtained from eight nonallergic patients who underwent elective polypectomy; mucosal specimens from the middle turbinates were acquired from eight subjects without NP as control tissues. The expression profile of SOD isoenzymes, SOD1, SOD2, and SOD3, in the nasal tissues was determined by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting (WB). NP in all eight of the NP patients manifested as severe or recurrent sinonasal polyposis clinically. The expression pattern of SOD isoenzymes evaluated by RT-PCR analysis indicated that the mean levels of SOD1 mRNA and, to a greater extent, SOD3 mRNA were higher in polyp tissues than in control tissues. There was no significant difference in the expression levels of SOD2 mRNA between the two groups. The data from ELISA and WB analysis showed that there were increased expressions of SOD1 and SOD3 protein in polyp tissues compared with the control tissues, but there was no difference in the expression of SOD2 protein between the two groups. The results from RT-PCR, ELISA, and WB were paralleled and revealed that the expressions of SOD1 and, to a greater extent, SOD3 were higher in polyp tissues than in the control group. The expressions of SOD3 and SOD1 were higher in polyp tissues. These results are consistent with previously reported data and support the hypothesis that there is increased oxidative stress in NP. Our data also suggest that the SODs might be important in the pathogenesis of NP; however, the roles these SOD isoforms, especially SOD3, play in both normal nasal mucosa and NP require further clarification.


[Structural state of the cardiomyocyte sarcolemma in animals of different ages].
Cardiomyocyte plasmalemma membranes of adult (12 months) and old (24-26 months) rats have been studied. Ageing is accompanied with an essential decrease of the content of the membrane protein SH-groups. We have found an increase in the fraction of strongly immobilized spin-labeled SH-groups, a decrease in that of unsaturated lipids, as well as an increase in that of lysophosphatidylcholine in old rats membranes. The pattern of the response of beta-adrenergic receptors to isoproterenol is changed with age. The mobility of spin probe 5NS in the membranes of old rats is lowered at 22.5 degrees C. However there is no statistically significant age difference in the spin-probe mobility at 37 degrees C. Possible role of lysophosphatidylcholine in the stabilization of membrane lipid "fluidity" at physiological temperatures is suggested.


[Incidence and clinical symptomatology of coronary heart disease in acquired valvular defects].
220 consecutive patients with acquired valvular defects were checked within the preoperative examination by means of heart catheter with regard to significant coronary stenoses. In these cases a relative frequency of typical and atypical angina pectoris troubles of 0.136 and 0.459, respectively, was the result. In contrast to this significant coronary stenoses could relatively infrequently made evident angiographically: 6/220 (= 0.027). In patients with valvular defects angina pectoris cannot be used as the leading symptom of an additionally existing coronary heart disease on account of bad sensitiveness.


Thiol proteases. Comparative studies based on the high-resolution structures of papain and actinidin, and on amino acid sequence information for cathepsins B and H, and stem bromelain.
An accurate three-dimensional structure is known for papain (1.65 A resolution) and actinidin (1.7 A). A detailed comparison of these two structures was performed to determine the effect of amino acid changes on the conformation. It appeared that, despite only 48% identity in their amino acid sequence, different crystallization conditions and different X-ray data collection techniques, their structures are surprisingly similar with a root-mean-square difference of 0.40 A between 76% of the main-chain atoms (differences less than 3 sigma). Insertions and deletions cause larger differences but they alter the conformation over a very limited range of two to three residues only. Conformations of identical side-chains are generally retained to the same extent as the main-chain conformation. If they do change, this is due to a modified local environment. Several examples are described. Spatial positions of hydrogen bonds are conserved to a greater extent than are the specific groups involved. The greatest structural similarity is found for the active site residues of papain and actinidin, for the internal water molecules and for the main-chain conformation of residues in alpha-helices and anti-parallel beta-sheet structure. This was reflected also in the similarity of the temperature factors. It suggests that the secondary structural elements form the skeleton of the molecule and that their interaction is the main factor in directing the fold of the polypeptide chain. Therefore, substitution of residues in the skeleton will, in general, have the most drastic effect on the conformation of the protein molecule. In papain and actinidin, some main-chain-side-chain hydrogen bonds are also strongly conserved and these may determine the folding of non-repetitive parts of the structure. Furthermore, we included primary structure information for three homologous thiol proteases: stem bromelain, and the cathepsins B and H. By combining the three-dimensional structural information for papain and actinidin with sequence homologies and identities, we conclude that the overall folding pattern of the polypeptide chain is grossly the same in all five proteases, and that they utilize the same catalytic mechanism.


[Patients with postpoliomyelitis syndrome in a rehabilitation hospital].
An increasing number of patients with suspected post-polio syndrome are referred to Sunnaas Rehabilitation Hospital. Using a case history as illustration, the article presents the model used for examination and treatment of these patients, based upon clinical observations, functional tests and comprehensive judgement by the rehabilitation team.


Microangiopathy and mild mixed neuromyopathic alterations in a patient with homozygous PIEZO-2 mutation.
We report a 9-year-old girl homozygous for a loss-of-function mutation in the PIEZO-2 gene. She showed generalized muscular hypotonia with severe scoliosis, joint deformities, deficient proprioceptive function and selective atrophy and signal alterations of both gastrocnemii on whole body MRI scan. Light microscopic and ultrastructural examination showed few atrophic fibres, abnormal mitochondria, focal myofibrillar disruption and endomysial capillary microangiopathy.


Presence of Penaeus monodon densovirus in the ovary of chronically infected P. monodon subadults.
Shrimp infected with Penaeus monodon densovirus (PmoDNV) usually display no specific gross signs, but heavy infections can kill postlarvae and retard juvenile growth. In the present study, samples of hepatopancreas, feces, gonads and hemolymph were isolated from male and female P. monodon subadults chronically infected by PmoDNV. Each sample of hepatopancreas and gonad was divided into 2 parts: one for PmoDNV detection by polymerase chain reaction (PCR), and the other for routine histology and immunohistochemistry. The frequency of positive findings via PCR assays was 92% in the hepatopancreas, 57% in feces, 50% in ovary, 35% in hemolymph and 0% in the testis. Using the densitometric value (DV) of the specific band for PmoDNV relative to that of the β-actin gene as an index of the viral load in the samples, no significant differences were observed among sample types and sexes. Hematoxylin-eosin staining of infected hepatopancreas revealed typical PmoDNV inclusions in the nuclei of infected cells. The ovaries with high DV (>1) contained various types of inclusions along the row of the follicular cells or possibly in the connective tissue cells surrounding the oocytes. Using immunohistochemistry with specific probes to detect PmoDNV proteins, a positive reaction was observed in viral inclusions found in infected hepatopancreas and in ovaries with high DV, specifically in the ovarian capsule, hemolymph, oocytes and nuclear inclusions. These results suggest that the localization of PmoDNV in P. monodon is not confined to the hepatopancreas, but rather that the virus can also occur in the ovary; hence, trans-ovarian, vertical transmission of the virus is highly possible.


The study design of ComAlong Toddler: a randomised controlled trial of an early communication intervention.
This study design article aims to describe a research study focused on evaluating the use of the Infant-Toddler Checklist to identify children at 18 months with early communication difficulties, and to study the ComAlong Toddler intervention for parents to support their child's communication development. Communication disorders are a common public health problem affecting up to 20% of children. Evidence points to the importance of early detection and intervention to improve young children's communicative abilities and decrease developmental delay. Early identification of communication difficulties is possible with instruments such as Infant-Toddler Checklist. The ComAlong Toddler intervention is tailored to the needs of parents of young children with communication delay before definitive diagnosis. The parents are provided with guidance in communication enhancing strategies during home visit and five group sessions. The study uses a prospective cohort design. Children were consecutively recruited during 2015-2017, and data will be collected 2015-2023. The screening was performed at the child health centre through use of the Infant-Toddler Checklist. An assessment and first consultation were then performed by a speech and language therapist for children with suspected communication delay according to the screen as well as for children referred for other reasons before the age of 2.5 years. Children with confirmed communication delay were randomised between two interventions: the ComAlong Toddler parental course or a telephone follow-up. Outcome measures include child communication and language skills and use of augmentative and alternative communication. To gain insight into the participants' perspectives, surveys have been collected from parents. The study will provide information regarding identification and intervention for 18-month old children with communication delay. ISRCTN13330627.


Electroconformational denaturation of membrane proteins.
Because of high electrical impedance of cell membrane, when living cells are exposed to an external electric field, the field-induced voltage drops will mainly occur on the cell membrane. In addition to Joule heating damage and electroporation of the cell membrane, the electric field-induced supraphysiological transmembrane potential may inevitably damage the membrane proteins, especially the voltage-dependent membrane proteins. That is because the charged particles in the amino acid of the membrane proteins and, in particular, the voltage-sensors in the voltage-dependent membrane proteins are vulnerable to the membrane potential. An intensive, brief electric shock may induce electroconformational damage or denaturation in the membrane proteins. As a result, the cell functions are significantly reduced. This electric field-induced denaturation in the membrane proteins strongly suggests a new underlying mechanism involved in electrical injury.


Impact of a human interest video on living-donor kidney donation rates.
Forty-five potential living donors participated in this study to see if a human interest video featuring living donors and recipients who had been through the transplant process would increase living-donor donation rates and knowledge about living-donor organ donation. While neither donation rates nor knowledge achieved statistical significance, the data clearly demonstrated a clinically significant (clinically relevant) increase in donation rates.


Some motifs were important for myostatin transcriptional regulation in sheep (Ovis aries).
Many motifs along the 1.2 kb myostatin promoter (MSTNpro) in sheep have been found by the MatInspecter program in our recent study. To further verify the role of the motifs and better understand the transcriptional regulation mechanism of the myostatin gene in sheep, the reporter gene EGFP (enhanced green fluorescent protein) was selected and the wild-type (W) vector MSTNPro(W)-EGFP or motif-mutational (M) vector MSTNPro(M)-EGFP were constructed. The transcriptional regulation activities were analyzed by detecting the fluorescence strength of EGFP in C2C12 myoblasts transfected with the vectors. The results showed that E-box (E) 3, E4, E5 and E7, particularly E3, E5 and E7, had important effects on the activity of the 1.2 kb sheep myostatin promoter. In addition, we also detected several other important motifs such as MTBF (muscle-specific Mt binding factor), MEF2 (myocyte enhancer factor 2), GRE (glucocorticoid response elements) and PRE (progesterone response elements) along the sheep myostatin promoter by the mutational analysis.


Synaptic plasticity with discrete state synapses.
Experimental observations on synaptic plasticity at individual glutamatergic synapses from the CA3 Shaffer collateral pathway onto CA1 pyramidal cells in the hippocampus suggest that the transitions in synaptic strength occur among discrete levels at individual synapses [C. C. H. Petersen, Proc. Natl. Acad. Sci. USA 85, 4732 (1998); O'Connor, Wittenberg, and Wang, D. H. O'Connor, Proc. Natl. Acad. Sci. USA (to be published); J. M. Montgomery and D. V. Madison, Trends Neurosci. 27, 744 (2004)]. This happens for both long term potentiation (LTP) and long term depression (LTD) induction protocols. O'Connor, Wittenberg, and Wang have argued that three states would account for their observations on individual synapses in the CA3-CA1 pathway. We develop a quantitative model of this three-state system with transitions among the states determined by a competition between kinases and phosphatases shown by D. H. O'Connor, to be determinant of LTP and LTD, respectively. Specific predictions for various plasticity protocols are given by coupling this description of discrete synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor ligand gated ion channel conductance changes to a model of postsynaptic membrane potential and associated intracellular calcium fluxes to yield the transition rates among the states. We then present various LTP and LTD induction protocols to the model system and report the resulting whole cell changes in AMPA conductance. We also examine the effect of our discrete state synaptic plasticity model on the synchronization of realistic oscillating neurons. We show that one-to-one synchronization is enhanced by the plasticity we discuss here and the presynaptic and postsynaptic oscillations are in phase. Synaptic strength saturates naturally in this model and does not require artificial upper or lower cutoffs, in contrast to earlier models of plasticity.


Detection of proximal secondary caries at cervical class II-amalgam restoration margins in vitro.
To compare the performance of LFpen (DIAGNOdent pen) with two different wedge-shaped tips to conventional bitewing radiography (BW) for detecting proximal secondary caries at the cervical margin of amalgam restorations in vitro. Seventy-five molars with class II amalgam restorations were selected. Depending on the marginal filling extension, data was subdivided into a crown group (C), when the filling ended in enamel, and into a root group (R), when the filling ended beyond the cementum-enamel junction. Bayesian analysis including calculation of the area under the receiver operating curve (AUC) was performed. Furthermore, Spearman correlations between caries and cofactors, such as presence of plaque or stain, occlusal ditching, marginal gap size, filling overhangs, and shortfalls, were calculated. Additionally, for group R the correlation coefficient between LFpen measurements and lesion depth was calculated. Histology served as gold standard. In group C both at the D1 and D3 levels, LFpen with two different tips showed a better performance than bitewing radiography (AUC at D1: 0.83/0.79 (LFpen) and 0.63 (BW); at D3: 0.66/0.66 (LFpen) and 0.53 (BW)). In group R, the respective AUC values were 0.53/0.56 (LF) and 0.59 (BW). A significant medium correlation was observed for occlusal ditching and proximal caries. Stain accumulation at the restoration margins especially in combination with filling overhangs interfered with LFpen readings, resulting in false positive measurements. Compared to BW, LFpen enhances the detection of secondary caries lesions at the cervical margin of amalgam restorations that do not extend below the cementum-enamel junction.


Twelve tips for preparing residents as teachers.
Residents are frequently identified by medical students as their most frequent and memorable teachers; residents also teach their peers, junior and senior colleagues, other health professionals, and their patients. Many will teach in their future practice. Developing the skills to become a teacher is an important part of postgraduate education, and warrants a systematic, planned approach that may include many complementary learning opportunities. Our purpose is to describe one such approach: a 4-week elective experience in medical education offered to postgraduate learners. The paper describes the background and goals for the elective, and the various steps in planning, implementing, and evaluating such a course, drawing on the literature and mining our own experience for examples. Specifically, we address the following: needs assessment; the determination and selection of content, sequence, and teaching and learning methods; the experiential learning opportunities offered; and the emphasis on the participants' developing self-awareness of themselves as teachers, and as part of a community of teachers. The program implementation, program evaluation, and response to feedback received are described. A 4-week elective experience in medical education was positively received by participants.


Behavioral flexibility of a group of bearded capuchin monkeys (Cebus libidinosus) in the National Park of Brasília (Brazil): consequences of cohabitation with visitors.
Increasing urbanization and deforestation have enhanced the opportunities of contact between humans and monkeys and the impact of human activities on primate behavior is receiving growing attention. This study explores whether activity budgets and diet of a group of capuchin monkeys (Cebus libidinosus) inhabiting the area of the swimming pools of the National Park of Brasília is affected by the presence of visitors providing food to them. During one year, both in the dry and the wet seasons, we scored capuchins' behavior via scan sampling every ten minutes. Results showed that this group spent less time foraging for wild foods than other comparable groups living in similar habitats. Moreover, capuchins relied more on human food during the dry season, when pulpy fruits were less available, than in the wet season. Our findings confirm other studies on different monkey species that have shown that access to human food decreases the time spent foraging for wild food and the home range size. They also show that capuchins are able to modify their diet, to exploit alternative food sources, and to change their activity budget in response to the availability of new food opportunities and to seasonal food availability.


Kinetic studies of atmospherically relevant silicon chemistry part I: silicon atom reactions.
Atomic silicon is generated by meteoric ablation in the Earth's upper atmosphere (70-110 km). The reactions of Si(3P(J)) atoms with several atmospherically relevant species were studied by the pulsed laser photolysis of a Si atom precursor (typically PheSiH3), followed by time-resolved laser induced fluorescence at 251.43 nm (Si(3p2 3P0 --> 4s 3P1)). This yielded: k(Si + O2, 190-500 K) = 9.49 x 10(-11) + 1.80 x 10(-10) x exp(-T/115 K) cm3 molecule(-1) s(-1) (uncertainty < or = +/- 15%), in good accord with recent high-level theoretical calculations but in marked disagreement with previous experimental work; k(Si + O3, 190-293 K) = (4.0 +/- 0.5) x 10(-10) cm3 molecule(-1) s(-1); k(Si + CO2, 293 K) < or = 1.2 x 10(-14) cm3 molecule(-1) s(-1); and k(Si + H2O, 293 K) < or = 2.6 x 10(-13) cm3 molecule(-1) s(-1). These results are explained using a combination of quantum chemistry calculations and long-range capture theory. The quenching rate coefficients k(Si(1D2) + N2, 293 K) = (4.0 +/- 0.7) x 10(-11) cm3 molecule(-1) s(-1) and k(Si(1D2) + H2O, 293 K) = (2.3 +/- 0.3) x 10(-10) cm3 molecule(-1) s(-1) were also determined.


Synthesis of (-)-conocarpan by two routes based on radical cyclization and establishment of its absolute configuration.
Two independent routes for the total synthesis of the bioactive neolignan (-)-conocarpan are described. The first (98% ee) is based on formal radical cyclization onto a benzene ring, and involves a 5-exo-trigonal closure onto a double bond restrained within a 6-membered ring. The second route (88% ee), which is shorter, is based on 5-exo-trigonal cyclization of an aryl radical onto a pendant terminal double bond. The two routes differ in their degree of stereoselectivity. The absolute configuration originally assigned to (+)-conocarpan had previously been called into question on the basis of empirical chiroptical rules; the present chemical work confirms the need for revision, and the assigned absolute configurations of several compounds correlated with (+)-conocarpan must also be changed.


Associations of IL-23R polymorphisms with ankylosing spondylitis in East Asian population: a new case-control study and a meta-analysis.
Interleukin-23 receptor (IL-23R) has been confirmed to be associated with ankylosing spondylitis (AS) in Caucasian. However, whether they are associated with AS in East Asian population remains unidentified. Here, we conducted a new case-control study investigating this relationship in Chinese Han population and then performed a meta-analysis in East Asian population. The Chinese Han study included 200 cases and 200 controls. Genotyping was completed using the chip-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Allelic associations were analysed using contingency tables. In the meta-analysis, 1384 cases and 1710 controls from five different studies and the new Chinese Han study were combined using Review Manager software Version 5.1.1. Mantel-Haenszel test was used to calculate fixed effects pooled ORs. No association with AS was observed in the Chinese Han study. Meta-analysis showed that no SNP was significantly associated with AS in East Asian population. In conclusion, we found no evidence for association between IL-23R and AS in East Asian population. Major attention should be paid to other genes belonged to IL-23 signalling pathway network in the future.


[A woman with gas behind her eye].
A 72-year-old woman had reduced vision due to orbital emphysema after a blow-out fracture.


Contribution of a snake venom toxin to myasthenia gravis: the discovery of alpha-bungarotoxin in Taiwan.
Myasthenia gravis (MG) is now recognized as an autoimmune disorder in which antibodies to acetylcholine (ACh) receptor lead to impairment of neuromuscular transmission. The discovery of alpha-bungarotoxin by Chang and Lee in 1963 has played a crucial role in establishing the new concept of MG. However, isolation of bungarotoxins from the venom of Taiwan banded krait, Bungarus multicinctus, was accomplished in the poorly funded and under equipped laboratory of the Department of Pharmacology, National Taiwan University, during the post-WWII period of economic depression and research isolation. Because alpha-bungarotoxin binds specifically and irreversibly with the muscle type nicotinic ACh receptor, it was used to localize ACh receptor and to isolate the ACh receptor protein, opening up a new era of receptor studies. It was also used to produce an antibody to ACh receptor and eventually an experimental autoimmune model of MG and clinical confirmation. The discovery of alpha-bungarotoxin has been considered the most important contribution to neurosciences from Taiwan.


Vaccines for the prevention of human papillomavirus and associated gynecologic diseases: a review.
Routine vaccination programs have had a substantial impact on reducing the prevalence of a variety of infections diseases. In light of the fact that human papillomavirus (HPV) is a prerequisite for virtually every case of cervical cancer and genital warts occurring worldwide, vaccination may be the most effective mechanism to prevent HPV infection and HPV-associated disease. HPV vaccines are created from noninfectious virus-like particles (VLPs) of the major capsid protein, L1, that closely mimic natural HPV virions. Proof-of-principle trials of monovalent vaccines that protect against high-risk HPV types such as HPV 16 or 18 have confirmed that intramuscular injection with VLPs induces the production of HPV type-specific neutralizing antibodies. A bivalent vaccine incorporating oncogenic HPV types 16 and 18 was shown to be safe, well tolerated, and 100% efficacious in preventing persistent HPV infection. A quadrivalent vaccine that protects against genital wart-causing HPV types (HPV 6 and 11) and oncogenic HPV types (HPV 16 and 18) demonstrated 100% efficacy in preventing clinical disease. Because VLP vaccines are prophylactic, vaccination before exposure to HPV will result in the greatest public health benefit; therefore, a successful vaccination program should target preadolescents and stress the importance of vaccination before sexual debut.


Perspectives on family caregiving of people aging with intellectual disability affected by dementia: Commentary from the International Summit on Intellectual Disability and Dementia.
This article, an output of the 2016 International Summit on Intellectual Disability and Dementia, examines familial caregiving situations within the context of a support-staging model for adults with intellectual disability (ID) affected by dementia. Seven narratives offer context to this support-staging model to interpret situations experienced by caregivers. The multidimensional model has two fundamental aspects: identifying the role and nature of caregiving as either primary (direct) or secondary (supportive); and defining how caregiving is influenced by stage of dementia. We propose staging can affect caregiving via different expressions: (1) the "diagnostic phase," (2) the "explorative phase," (3) the "adaptive phase," and (4) the "closure phase." The international narratives illustrate direct and indirect caregiving with commonality being extent of caregiver involvement and attention to the needs of an adult with ID. We conclude that the model is the first to empirically formalize the variability of caregiving within families of people with ID that is distinct from other caregiving groups, and that many of these caregivers have idiosyncratic needs. A support-staging model that recognizes the changing roles and demands of carers of people with ID and dementia can be useful in constructing research, defining family-based support services, and setting public policy.


The frequency and outcome of uveitis in patients with newly diagnosed juvenile idiopathic arthritis in two 4-year cohorts from 1990-1993 and 2000-2003.
To retrospectively compare the frequency and outcome of uveitis between two cohorts of patients with newly-onset juvenile idiopathic arthritis (JIA) separated by a 10 year interval. The diagnosis of JIA was made in 239 patients in 1990-1993 and in 240 patients in 2000-2003 by paediatric rheumatologists at the Rheumatism Foundation Hospital, Heinola, Finland. An ophthalmologist examined all the patients regularly and diagnosed uveitis. The demographics of the patients, type of JIA, frequency, medical treatment and outcome of uveitis were documented. The main outcome measures were the frequency and outcome of uveitis, the number of complications and the best corrected visual acuity (BCVA), need of corticosteroids and other immunosuppressive treatment. The frequency of uveitis was higher (25% vs. 18%) in the earlier cohort. The visual outcome was ≥0.5 in all JIA-uveitis patients except one in the earlier cohort. Complications were fewer (21% vs. 35%) and uveitis was milder according to the Standardisation of Uveitis Nomenclature (SUN) criteria in the later cohort. Remission of uveitis (33% vs. 42%) and arthritis (20% vs. 23%) in JIA-uveitis patients was similar in both cohorts after a follow-up of 6.6 and 5.9 years, respectively. Systemic corticosteroids were more commonly used (25% vs. 7%) in JIA-uveitis patients of the earlier cohort but the use of methotrexate was equal in both cohorts (65% vs. 67%). In this study with early and aggressive treatment and close monitoring the outcome of JIA-uveitis patients was favourable and visual loss was avoided in most cases.


Efficiency of tabu-search-based conformational search algorithms.
Efficient conformational search or sampling approaches play an integral role in molecular modeling, leading to a strong demand for even faster and more reliable conformer search algorithms. This article compares the efficiency of a molecular dynamics method, a simulated annealing method, and the basin hopping (BH) approach (which are widely used in this field) with a previously suggested tabu-search-based approach called gradient only tabu search (GOTS). The study emphasizes the success of the GOTS procedure and, more importantly, shows that an approach which combines BH and GOTS outperforms the single methods in efficiency and speed. We also show that ring structures built by a hydrogen bond are useful as starting points for conformational search investigations of peptides and organic ligands with biological activities, especially in structures that contain multiple rings.


[The acute cerebellar ataxia, reccurrence of disease after 5 years--a case report].
Acute cerebellitis, also known as acute cerebellar ataxia, is a rare inflammatory syndrome characterized by cerebellar dysfunction. It typically occurs as a primary infectious, post-infectious or post vaccination disorder, typically in early childhood. The author presents a case of recurrent, acute cerebellar ataxia in a 20-year-old woman. In the described case the first event of acute cerebellar ataxia occured at the age of 15. The disease lasted 3 weeks and symptoms disappeared entirely. The similar symptoms recurred after 5 years but they were more pronounced and accompanied by pleocytosis, high protein level and low glucose level in cerebrospinal fluid. The symptoms disappeared entirely after 2 months of treatment.