Gut neuroendocrine cells: relationship to the proliferative activity and apoptosis of mucous epitheliocytes in aging.
Diffuse neuroendocrine system (DNES) cells regulate homeostasis via neurocrine, endocrine and paracrine mechanisms. Extensive effects of peptide hormones and biogenic amines necessitate studying of DNES cell biology in aging. In this connection, the functional morphology of gut neuroendocrine cells (NEC), proliferative activity and apoptosis of mucous epithelial cells in aging have been studied. The study was performed on BALB/c-nu mice of 4, 21 and 34 months of age. NEC, proliferative activity and apoptosis of mucous epitheliocytes in stomach and duodenum have been studied by histochemical, immunohistochemical and morphometrical methods. The total number of NEC shows an increasing trend with advancing age. However, the different types of NEC elicit differential patterns. The total number of epithelial cell nuclei does not show any statistically significant difference during aging. The proliferative activity of mucous epitheliocytes also shows no difference among the three animal groups studied. On the contrary, the apoptotic index increases with advancing age. The results demonstrate that various gut NEC show differential behavior with age and their time-courses are dependent on the site of location (stomach or duodenum). The picture seems quite complex to allow a comprehensive interpretation, nonetheless it gives us some useful indications for further investigation. In fact, since the gut does not show evident gross age-related physiological changes, modifications with age in specific biological parameters can suggest the key mechanisms of compensative regulatory processes possibly acting during aging.


Economic growth, biodiversity loss and conservation effort.
This paper investigates the relationship between economic growth, biodiversity loss and efforts to conserve biodiversity using a combination of panel and cross section data. If economic growth is a cause of biodiversity loss through habitat transformation and other means, then we would expect an inverse relationship. But if higher levels of income are associated with increasing real demand for biodiversity conservation, then investment to protect remaining diversity should grow and the rate of biodiversity loss should slow with growth. Initially, economic growth and biodiversity loss are examined within the framework of the environmental Kuznets hypothesis. Biodiversity is represented by predicted species richness, generated for tropical terrestrial biodiversity using a species-area relationship. The environmental Kuznets hypothesis is investigated with reference to comparison of fixed and random effects models to allow the relationship to vary for each country. It is concluded that an environmental Kuznets curve between income and rates of loss of habitat and species does not exist in this case. The role of conservation effort in addressing environmental problems is examined through state protection of land and the regulation of trade in endangered species, two important means of biodiversity conservation. This analysis shows that the extent of government environmental policy increases with economic development. We argue that, although the data are problematic, the implications of these models is that conservation effort can only ever result in a partial deceleration of biodiversity decline partly because protected areas serve multiple functions and are not necessarily designated to protect biodiversity. Nevertheless institutional and policy response components of the income biodiversity relationship are important but are not well captured through cross-country regression analysis.


Electronic structure calculations permit identification of the driving forces behind frequency shifts in transition metal monocarbonyls.
We report the adiabatic energy decomposition analysis (EDA) of density functional theory (DFT) results, shedding light on the physical content of binding energies and carbon monoxide (CO) frequency (υCO) shifts in select first-row transition metal monocarbonyls (MCOs; M = Ti-, V-, Cr-, Co-, Ni-, Cu-, V, Cr, Mn, Ni, Cu, Zn, Cr+, Mn+, Fe+, Cu+, and Zn+). This approach allows for the direct decomposition of υCO, in contrast to previous studies of these systems. Neutral, anionic, and cationic systems are compared, and our results indicate that the relative importance of electrostatic interactions, intramolecular orbital polarization, and charge transfer can vary significantly with the charge and electron configuration of the metal participating in binding. Various anomalous systems are also discussed and incorporated into a general model of MCO binding. Electrostatic interactions and orbital polarization are found to promote blue shifts in υCO, while charge transfer effects encourage υCO red-shifting; previously reported values of υCO are found to be a result of a complex but quantifiable interplay between these physical components. Our computations indicate that CuCO- and ZnCO possess triplet ground states, and also that CrCO- exhibits a non-linear geometry, all in contrast to previous computational results. Advantages and limitations of this model as an approximation to more complicated systems, like those implicated in heterogeneous catalysis, are discussed. We also report benchmark results for MCO geometries, binding energies, and harmonic CO frequencies, and discuss the validity of single-reference wave function and DFT approaches to the study of these transition metal systems.


Cell proliferation index determination by immunohistochemical detection of hCDC47 protein.
A member of the human minichromosome maintenance complex protein family, hCDC47 (alias MCM7) has been identified as a component of the regulatory mechanism in cell proliferation. The expression of this protein, as determined by immunohistochemistry, was investigated to determine its application as a proliferation marker. A mouse monoclonal antibody (Clone 47DC141, NeoMarkers, Fremont CA) raised against recombinant hCDC47 protein was tested against a wide range of tissues. Immunoreaction patterns were determined in normal and neoplastic, human tissues, including skin, tonsils and lymph nodes, primary, and metastatic brain tumors. The protein was detected in the nuclei of both, normal and neoplastic proliferating cells. Similarly, we also examined the distribution of hCDC47 in normal rat and mouse tissues, and rodent and human tumors grown in nude mice.The pattern of immunolocalization was identical to that seen in human tissue, with positive nuclear immunoreaction readily identified in proliferating cells. Western immunoblot was carried out on extracts from PANC cells (human pancreatic adenocarcinoma cell line) to confirm the specificity of the protein. To correlate Ki67 protein immunoexpression with hCDC47 antibody reactivity, semiquantitative comparisons were carried out on parallel tissue sections. There was excellent correlation in the distribution pattern of the 2 markers, although hCDC47 was more sensitive.Thus this marker may have important clinical and research applications because of its activity in formalin-fixed, paraffin-embedded, proliferating, normal, and neoplastic tissue. More significantly, its application to animal tissue makes it a reliable and easy to use, proliferation marker for experimental studies.


The Involvement of a Concerned Significant Other in Gambling Disorder Treatment Outcome.
Interpersonal distress is a common feature in gambling disorder and adding a concerned significant other (CSO) to the recovery process could be an effective tool for improving treatment outcome. However, little empirical evidence is available regarding the effectiveness of including a CSO to interventions. We aimed to compare treatment outcomes (i.e. compliance with therapy guidelines, dropout from treatment, and relapse during treatment) in a CBT program involving a CSO to CBT treatment as usual (TAU) without a CSO. The sample comprised male gambling disorder patients (N = 675). The manualized CBT intervention consisted of 16 weekly outpatient group sessions and a 3-month follow-up period. Patient CSOs attended a predetermined number of sessions with the patient and were provided with resources to acquire a better understanding of the disorder, to manage risk situations, and to aid patients in adhering to treatment guidelines. Patients with a CSO had significant higher treatment attendance and reduced dropout compared to patients receiving TAU. Moreover, patients whose spouse was involved in the treatment program were less likely to relapse and adhered to the treatment guidelines more than those with a non-spousal CSO. Our results suggest that incorporating interpersonal support to gambling disorder interventions could potentially improve treatment outcomes.


Spreading speed, traveling waves, and minimal domain size in impulsive reaction-diffusion models.
How growth, mortality, and dispersal in a species affect the species' spread and persistence constitutes a central problem in spatial ecology. We propose impulsive reaction-diffusion equation models for species with distinct reproductive and dispersal stages. These models can describe a seasonal birth pulse plus nonlinear mortality and dispersal throughout the year. Alternatively, they can describe seasonal harvesting, plus nonlinear birth and mortality as well as dispersal throughout the year. The population dynamics in the seasonal pulse is described by a discrete map that gives the density of the population at the end of a pulse as a possibly nonmonotone function of the density of the population at the beginning of the pulse. The dynamics in the dispersal stage is governed by a nonlinear reaction-diffusion equation in a bounded or unbounded domain. We develop a spatially explicit theoretical framework that links species vital rates (mortality or fecundity) and dispersal characteristics with species' spreading speeds, traveling wave speeds, as well as minimal domain size for species persistence. We provide an explicit formula for the spreading speed in terms of model parameters, and show that the spreading speed can be characterized as the slowest speed of a class of traveling wave solutions. We also give an explicit formula for the minimal domain size using model parameters. Our results show how the diffusion coefficient, and the combination of discrete- and continuous-time growth and mortality determine the spread and persistence dynamics of the population in a wide variety of ecological scenarios. Numerical simulations are presented to demonstrate the theoretical results.


Adverse Effects of Wi-Fi Radiation on Male Reproductive System: A Systematic Review.
Extensive use of Wi-Fi has contributed to radiofrequency electromagnetic radiation (RF-EMR) pollution in environment. Various studies have been conducted to evaluate the effect of RF-EMR emitted by Wi-Fi transmitter on male reproduction health. However, there are conflicting findings between studies. Thus, this review aims to elucidate the possible effects of 2.45 GHz Wi-Fi exposure on both animal and human male reproductive system. A computerized database search performed through MEDLINE via Ovid and PUBMED with the following set of keywords: 'Wi-Fi or WiFi or wireless fidelity or Wi-Fi router or WiFi router or electromagnetic or radiofrequency radiation' AND 'sperm or spermatozoa or spermatogenesis or semen or seminal plasma or testes or testis or testosterone or male reproduction' had returned 526 articles. Only 17 studies conformed to pre-set inclusion criterion. Additional records identified through Google Scholar and reviewed article further revealed six eligible articles. A total of 23 articles were used for data extraction, including 15 studies on rats, three studies on mice, and five studies on human health. Sperm count, motility and DNA integrity were the most affected parameters when exposed to RF-EMR emitted by Wi-Fi transmitter. Unfortunately, sperm viability and morphology were inconclusive. Structural and/or physiological analyses of the testes showed degenerative changes, reduced testosterone level, increased apoptotic cells, and DNA damage. These effects were mainly due to the elevation of testicular temperature and oxidative stress activity. In conclusion, exposure towards 2.45 GHz RF-EMR emitted by Wi-Fi transmitter is hazardous on the male reproductive system.


The Role of the PI3K Signaling Pathway in CD4(+) T Cell Differentiation and Function.
The relative activity of regulatory versus conventional CD4(+) T cells ultimately maintains the delicate balance between immune tolerance and inflammation. At the molecular level, the activity of phosphatidylinositol 3-kinase (PI3K) and its downstream positive and negative regulators has a major role in controlling the balance between immune regulation and activation of different subsets of effector CD4(+) T cells. In contrast to effector T cells which require activation of the PI3K to differentiate and mediate their effector function, regulatory T cells rely on minimal activation of this pathway to develop and maintain their characteristic phenotype, function, and metabolic state. In this review, we discuss the role of the PI3K signaling pathway in CD4(+) T cell differentiation and function, and focus on how modulation of this pathway in T cells can alter the outcome of an immune response, ultimately tipping the balance between tolerance and inflammation.


Urticaria and infections.
Urticaria is a group of diseases that share a distinct skin reaction pattern. Triggering of urticaria by infections has been discussed for many years but the exact role and pathogenesis of mast cell activation by infectious processes is unclear. In spontaneous acute urticaria there is no doubt for a causal relationship to infections and all chronic urticaria must have started as acute. Whereas in physical or distinct urticaria subtypes the evidence for infections is sparse, remission of annoying spontaneous chronic urticaria has been reported after successful treatment of persistent infections. Current summarizing available studies that evaluated the course of the chronic urticaria after proven Helicobacter eradication demonstrate a statistically significant benefit compared to untreated patients or Helicobacter-negative controls without urticaria (p < 0.001). Since infections can be easily treated some diagnostic procedures should be included in the routine work-up, especially the search for Helicobacter pylori. This review will update the reader regarding the role of infections in different urticaria subtypes.


Exposure of rats to inhalational anesthetics alters the hepatobiliary clearance of cholephilic xenobiotics.
Several recent studies indicate that anesthesia-induced alteration of UDP-glucuronic acid concentrations can affect the rate of xenobiotic glucuronidation by UDP-glucuronosyltransferases. Other data demonstrate that the biliary excretion of several cholephilic drugs is depressed in rats anesthetized with diethyl ether. The present study has examined the effect of 2% halothane, 1.5% isoflurane, 2% enflurane and 3% sevoflurane on the clearance and biliary excretion of acetaminophen, digoxin, phenol red and phenol-3,6-dibromphthalein disulfonate. All volatile anesthetics reduced hepatic UDP-glucuronic acid concentrations 50 to 75%. Biliary excretion of acetaminophen as well as the glucuronide and sulfate conjugates was depressed by all anesthetics for about 1 hr, whereas biliary excretion of the glutathione conjugate was increased during this time. Although total clearance, elimination half-life and steady-state volume of distribution were not altered, biliary clearance of acetaminophen was decreased by 39 to 50%. Formation of the glucuronide conjugate of phenol red and its biliary excretion were depressed by all volatile anesthetics; however, total clearance was increased by 15 to 25% during isoflurane or sevoflurane anesthesia. Total clearance and steady-state volume of distribution of digoxin were decreased only in rats exposed to halothane. There were no changes in biliary excretion. Urinary clearance of digoxin was increased by all volatile anesthetics, whereas biliary clearance was decreased by halothane and enflurane. Biliary excretion, clearance and volume of distribution of phenol-3,6-dibromphthalein disulfonate were not altered by the anesthetics. These data indicate that the hepatobiliary elimination of the glucuronidated metabolites is reduced in rats exposed to volatile anesthetics.


Parent-of-origin effects at the major histocompatibility complex in multiple sclerosis.
Multiple sclerosis (MS) susceptibility is characterized by maternal parent-of-origin effects and increased female penetrance. In 7796 individuals from 1797 MS families (affected individuals n = 2954), we further implicate epigenetic modifications within major histocompatibility complex (MHC) class II haplotypes as mediating these phenomena. Affected individuals with the main MS-associated allele HLA-DRB1*15 had a higher female-to-male ratio versus those lacking it (P = 0.00023). Distorted transmission of MHC haplotypes by both parent-of-origin and gender-of-affected-offspring was most evident in the maternal HLA-DRB1*15 transmission to affected female offspring (OR = 3.31, 95% CI = 2.59-4.24) contrasting with similarity among maternal transmission to affected male offspring (OR = 2.13, 95% CI = 1.44-3.14), paternal transmissions to affected female (OR = 2.14, 95% CI = 1.64-2.78) and male (OR = 2.16, 95% CI = 1.37-3.39) offspring. Significant parent-of-origin effects were observed in affected females (maternal: P = 9.33 x 10(-42); paternal: P = 1.12 x 10(-15); comparison: P = 0.0014), but not in affected males (maternal: P = 6.70 x 10(-8); paternal: P = 2.54 x 10(-6); comparison: P = 0.95). Conditional logistic regression analysis revealed further differential risk of HLA diplotypes. Risks for HLA-DRB1*15 and likely for other HLA-DRB1 haplotypes were restricted by (i) parent-of-origin, (ii) gender-of-offspring and (iii) trans epistasis in offspring. These findings may illuminate the gender bias characterizing autoimmunity overall. They raise questions about the concept of restricted antigen presentation in autoimmunity and suggest that gender-specific epigenetic interactions may be the driving forces behind the MHC haplotypic associations. Haplotype-specific epigenetic modifications at MHC class II and their decay appear to be at the heart of MS pathogenesis and inheritance of risk, providing the focus for gene-environment interactions that determine susceptibility and resistance.


A plant pathogen virulence factor inhibits the eukaryotic proteasome by a novel mechanism.
Pathogenic bacteria often use effector molecules to increase virulence. In most cases, the mode of action of effectors remains unknown. Strains of Pseudomonas syringae pv. syringae (Pss) secrete syringolin A (SylA), a product of a mixed non-ribosomal peptide/polyketide synthetase, in planta. Here we identify SylA as a virulence factor because a SylA-negative mutant in Pss strain B728a obtained by gene disruption was markedly less virulent on its host, Phaseolus vulgaris (bean). We show that SylA irreversibly inhibits all three catalytic activities of eukaryotic proteasomes, thus adding proteasome inhibition to the repertoire of modes of action of virulence factors. The crystal structure of the yeast proteasome in complex with SylA revealed a novel mechanism of covalent binding to the catalytic subunits. Thus, SylA defines a new class of proteasome inhibitors that includes glidobactin A (GlbA), a structurally related compound from an unknown species of the order Burkholderiales, for which we demonstrate a similar proteasome inhibition mechanism. As proteasome inhibitors are a promising class of anti-tumour agents, the discovery of a novel family of inhibitory natural products, which we refer to as syrbactins, may also have implications for the development of anti-cancer drugs. Homologues of SylA and GlbA synthetase genes are found in some other pathogenic bacteria, including the human pathogen Burkholderia pseudomallei, the causative agent of melioidosis. It is thus possible that these bacteria are capable of producing proteasome inhibitors of the syrbactin class.


Relationship Between Spiritual Coping and Survival in Patients with HIV.
Studies of spirituality in initially healthy people have shown a survival advantage, yet there are fewer research studies in the medically ill, despite the widespread use of spirituality/religiousness to cope with serious physical illness. In addition, many studies have used limited measures such as religious service attendance. We aimed to examine if, independent of medication adherence, the use of spirituality/religiousness to cope with HIV predicts survival over 17 years. This was a longitudinal study, started in 1997. Study materials were administered semi annually. A diverse sample of 177 HIV patients initially in the mid-stage of disease (150-500 CD4-cells/mm(3); no prior AIDS-defining symptoms) participated in the study. Participants were administered a battery of psychosocial questionnaires and a blood draw. They completed interviews and essays to assess current stressors. Spiritual coping (overall/strategies) was rated by qualitative content analysis of interviews regarding stress and coping with HIV, and essays. Controlling for medical variables (baseline CD4/viral load) and demographics, Cox regression analyses showed that overall positive spiritual coping significantly predicted greater survival over 17 years (mortality HR = 0.56, p = 0.039). Findings held even after controlling for health behaviors (medication adherence, substance use) and social support. Particular spiritual coping strategies that predicted longer survival included spiritual practices (HR = 0.26, p < 0.001), spiritual reframing (HR = 0.27, p = 0.006), overcoming spiritual guilt (HR = 0.24, p < 0.001), spiritual gratitude (HR = 0.40, p = 0.002), and spiritual empowerment (HR = 0.52, p = 0.024), indicating that people using these strategies were 2-4 times more likely to survive. To our knowledge this is the first study showing a prospective relationship of spiritual coping in people who are medically ill with survival over such a long period of time, and also specifically identifies several strategies of spirituality that may be beneficial.


GhABP19, a Novel Germin-Like Protein From Gossypium hirsutum, Plays an Important Role in the Regulation of Resistance to Verticillium and Fusarium Wilt Pathogens.
Germin-like proteins (GLPs) are water-soluble plant glycoproteins belonging to the cupin superfamily. The important role of GLPs in plant responses against various abiotic and biotic stresses, especially pathogens, is well validated. However, little is known about cotton GLPs in relation to fungal pathogens. Here, a novel GLP gene was isolated from Gossypium hirsutum and designated as GhABP19. The expression of GhABP19 was upregulated in cotton plants inoculated with Verticillium dahliae and Fusarium oxysporum and in response to treatment with jasmonic acid (JA) but was suppressed in response to salicylic acid treatment. A relatively small transient increase in GhABP19 was seen in H2O2 treated samples. The three-dimensional structure prediction of the GhABP19 protein indicated that the protein has three histidine and one glutamate residues responsible for metal ion binding and superoxide dismutase (SOD) activity. Purified recombinant GhABP19 exhibits SOD activity and could inhibit growth of V. dahliae, F. oxysporum, Rhizoctonia solani, Botrytis cinerea, and Valsa mali in vitro. To further verify the role of GhABP19 in fungal resistance, GhABP19-overexpressing Arabidopsis plants and GhABP19-silenced cotton plants were developed. GhABP19-transgenic Arabidopsis lines showed much stronger resistance to V. dahliae and F. oxysporum infection than control (empty vector) plants did. On the contrary, silencing of GhABP19 in cotton conferred enhanced susceptibility to fungal pathogens, which resulted in necrosis and wilt on leaves and vascular discoloration in GhABP19-silenced cotton plants. The H2O2 content and endogenous SOD activity were affected by GhABP19 expression levels in Arabidopsis and cotton plants after inoculation with V. dahliae and F. oxysporum, respectively. Furthermore, GhABP19 overexpression or silencing resulted in activation or suppression of JA-mediated signaling, respectively. Thus, GhABP19 plays important roles in the regulation of resistance to verticillium and fusarium wilt in plants. These modulatory roles were exerted by its SOD activity and ability to activate the JA pathway. All results suggest that GhABP19 was involved in plant disease resistance.


The sensory interactions of organic acids and various flavors in ramen soup systems.
This study was conducted to investigate the sensory interactions between various organic acids and flavorants in 3 types of ramen soup ('beef,' seafood, and 'kimchi') when types and levels of organic acids (citric, malic, and lactic) varied. For 'beef' and seafood ramen soup, weak suprathreshold levels of acids (0.0039% to 0.0071%) were applied to the system and medium suprathreshold of acids (0.0128% to 0.0299%) were applied to the kimchi ramen soup. The amount of acid applied to each system was chosen based on the equiweight level. Descriptive analyses were performed separately for each ramen soup system using 8 trained panelists. A total of 11, 13, and 12 flavor descriptors were generated for 'beef,' seafood, and 'kimchi' soup, respectively. Analysis of variance was conducted to evaluate the effect of organic acid on the sensory characteristics of ramen soup. Principal component analysis was conducted to summarize the relationship between the soup samples and attributes. The effect of organic acids on the flavor attributes of ramen soup was dependent on the soup system as well as adding levels of acid. Addition of lactic acid power (at 0.0066%) in 'beef'ramen soup showed enhancement effect on the sour, salty, beefy, 'mushroom' flavor, and fermented soybean paste soup flavor, whereas lactic acid powder (at 0.0071%) showed enhancement effect only on the sour and fermented soybean paste soup flavor in seafood ramen soup due to the strong 'hot' flavor characteristics of the soup. In kimchi ramen soup, flavor attributes congruent to sourness were enhanced by the addition of organic acids to the system.


Traveling waves and spread rates for a West Nile virus model.
A reaction-diffusion model for the spatial spread of West Nile virus is developed and analysed. Infection dynamics are based on a modified version of a model for cross infection between birds and mosquitoes (Wonham et al., 2004, An epidemiological model for West-Nile virus: Invasion analysis and control application. Proc. R. Soc. Lond. B 271), and diffusion terms describe movement of birds and mosquitoes. Working with a simplified version of the model, the cooperative nature of cross-infection dynamics is utilized to prove the existence of traveling waves and to calculate the spatial spread rate of infection. Comparison theorem results are used to show that the spread rate of the simplified model may provide an upper bound for the spread rate of a more realistic and complex version of the model.


White Matter Changes in Cervical Dystonia Relate to Clinical Effectiveness of Botulinum Toxin Treatment.
In a previous report showing white matter microstructural hemispheric asymmetries medial to the pallidum in focal dystonias, we showed preliminary evidence that this abnormality was reduced 4 weeks after botulinum toxin (BTX) injections. In the current study we report the completed treatment study in a full-size cohort of CD patients (n = 14). In addition to showing a shift toward normalization of the hemispheric asymmetry, we evaluated clinical relevance of these findings by relating white matter changes to degree of symptom improvement. We also evaluated whether the magnitude of the white matter asymmetry before treatment was related to severity, laterality, duration of dystonia, and/or number of previous BTX injections. Our results confirm the findings of our preliminary report: we observed significant fractional anisotropy (FA) changes medial to the pallidum 4 weeks after BTX in CD participants that were not observed in controls scanned at the same interval. There was a significant relationship between magnitude of hemispheric asymmetry and dystonia symptom improvement, as measured by percent reduction in dystonia scale scores. There was also a trend toward a relationship between magnitude of pre-injection white matter asymmetry and symptom severity, but not symptom laterality, disorder duration, or number of previous BTX injections. Post-hoc analyses suggested the FA changes at least partially reflected changes in pathophysiology, but a dissociation between patient perception of benefit from injections and FA changes suggested the changes did not reflect changes to the primary "driver" of the dystonia. In contrast, there were no changes or group differences in DTI diffusivity measures, suggesting the hemispheric asymmetry in CD does not reflect irreversible white matter tissue loss. These findings support the hypothesis that central nervous system white matter changes are involved in the mechanism by which BTX exerts clinical benefit.


Quantum Circuits Assisted by Local Operations and Classical Communication: Transformations and Phases of Matter.
We introduce deterministic state-transformation protocols between many-body quantum states that can be implemented by low-depth quantum circuits followed by local operations and classical communication. We show that this gives rise to a classification of phases in which topologically ordered states or other paradigmatic entangled states become trivial. We also investigate how the set of unitary operations is enhanced by local operations and classical communication in this scenario, allowing one to perform certain large-depth quantum circuits in terms of low-depth ones.


Comparison of invasive and non-invasive pressure gradients in aortic arch obstruction.
Aortic arch obstruction can be evaluated by catheter peak-to-peak gradient or by Doppler peak instantaneous pressure gradient. Previous studies have shown moderate correlation in discrete coarctation, but few have assessed correlation in patients with more complex aortic reconstruction. We carried out retrospective comparison of cardiac catheterisations and pre- and post-catheterisation echocardiograms in 60 patients with native/recurrent coarctation or aortic reconstruction. Aortic arch obstruction was defined as peak-to-peak gradient ⩾25 mmHg in patients with native/recurrent coarctation and ⩾10 mmHg in aortic reconstruction. Diastolic continuation of flow was not associated with aortic arch obstruction in either group. Doppler peak instantaneous pressure gradient, with and without the expanded Bernoulli equation, weakly correlated with peak-to-peak gradient even in patients with a normal cardiac index (r=0.36, p=0.016, and r=0.49, p=0.001, respectively). Receiver operating characteristic curve analysis identified an area under the curve of 0.61 for patients with all types of obstruction, with a cut-off point of 45 mmHg correctly classifying 64% of patients with arch obstruction (sensitivity 39%, specificity 89%). In patients with aortic arch reconstruction who had a cardiac index ⩾3 L/min/m², a cut-off point of 23 mmHg correctly classified 69% of patients (71% sensitivity, 50% specificity) with an area under the curve of 0.82. The non-invasive assessment of aortic obstruction remains challenging. The greatest correlation of Doppler indices was noted in patients with aortic reconstruction and a normal cardiac index.


Molecular recognition by self-assembled monolayers of cavitand receptors.
It is shown by angle-resolved x-ray photoelectron spectroscopy that cavitands derived from resorcin[4]arenes provided with four dialkylsulfide chains form stable monolayers on gold surfaces that are well organized by self-assembly. The cavitand headgroups at the surface of the resorcin[4]arene monolayer act as molecular recognition sites for small organic molecules with remarkable selectivity for perchloroethylene (C(2)Cl(4)). Comparative thermal desorption experiments indicate binding sites with high interaction energies of C(2)Cl(4) at the surface of the resorcin[4]arene monolayers. Fast and reversible "host-guest" interactions were found by the monitoring of extremely small mass changes (in the nanogram range) with a quartz microbalance oscillator provided with gold electrodes coated by resorcin[4]arene monolayers.


Optimizing CRT - Do We Need More Leads and Delivery Methods.
Cardiac resynchronization therapy (CRT) is an established therapeutic option in symptomatic heart failure with reduced ejection fraction and evidence of left ventricular (LV) conduction delay (QRS width ≥120 ms), especially when typical left bundle branch block is present. The rationale behind CRT is restoration of aberrant LV electrical activation. As there is considerable heterogeneity of the LV electrical activation pattern among CRT candidates, an individualized approach with targeting of the LV lead in the region of latest electrical activation while avoiding scar tissue may enhance CRT response. Echocardiography, electro anatomic mapping, and cardiac magnetic resonance imaging with late gadolinium enhancement are helpful to guide such targeted LV lead placement. However, an important limitation remains the anatomy of the coronary sinus, which often does not allow concordant LV lead placement in the optimal region. Epicardial LV lead placement through minimal invasive surgery or endocardial LV lead placement through transseptal punction may overcome this limitation, obviously with an increased complication risk. Furthermore, recent pacing algorithms suggest superiority of LV-only versus biventricular pacing in patients with preserved atrio ventricular (AV) conduction and a typical LBBB pattern. Finally, pacing from only one LV site might not overcome the wide electrical dispersion often seen in patients with LV conduction delays. Therefore, multisite pacing has gained significant interest to improve CRT response. The use of multiple LV leads may potentially lead to more favorable reverse remodeling, improved functional capacity and quality of life in CRT candidates, but adverse events and a shorter battery span are more frequent because of the extra lead. The use of one multipolar LV lead increases the number of pacing configurations within the same coronary sinus side branch (within small distances from each other) without the use of an additional lead. Small observational studies suggest that more effective resynchronization can be achieved with this approach. Finally, there are many reasons for non effective CRT delivery in carefully selected patients with an adequately implanted device. Multidisciplinary, post implantation care inside a dedicated CRT clinic ensures optimal CRT delivery, improves response rate and should be considered standard of care.


Music therapy: a valuable adjunct in the oncology setting.
Music therapy is the supervised and therapeutic use of music by a credentialed therapist to promote positive clinical outcomes. It can be a valuable form of complementary medicine in the oncology setting to decrease patient stress and anxiety, relieve pain and nausea, provide distraction, alleviate depression, and promote the expression of feelings. The music therapist assesses the patient and consults other members of the multidisciplinary team to create a therapeutic treatment plan. Music therapists design music sessions based on patients' needs and their intended therapeutic goals. Patients can participate actively or passively in individual or group sessions. Only a credentialed music therapist can provide safe and beneficial music therapy interventions.


Immediate loading of tooth-implant-supported telescopic mandibular prostheses.
Extractions in partially edentulous patients often lead to insufficient stability of an existing partial prosthesis and a need for additional anchorage. Implants may therefore be placed as supplementary abutments to increase patient comfort and satisfaction. The aim of this study was to evaluate the long-term clinical outcome of implants combined with teeth to support telescopic abutment-retained removable full-arch prostheses under an immediate functional loading protocol. The present retrospective study included implants placed and connected via removable prostheses with periodontally healthy teeth immediately postplacement using prefabricated abutments. Secondary copings, precisely fit to the abutments, were placed and the partial dentures were relined chairside. The prosthetic restorations were not removed for 10 days. Clinical and radiographic evaluations of implants loaded for at least 2 years were performed. One hundred ten implants with a progressive thread design (Ankylos, Dentsply) were placed in 55 patients (mean age, 63.51±9.95 years). Twenty-five implants were placed in fresh extraction sockets (22.73%) and 85 implants were placed in healed ridges. All implants were placed 2 to 3 mm subcrestally (measured from the midfacial bone level). After a mean follow-up of 61.58±28.47 months (range, 24 to 125 months), there were only three failures (2.73%); another six implants (5.45%) displayed crestal bone loss greater than 2 mm but remained stable. Therefore, the failure rate was 8.18% for the entire observation period of 5.13 years. The success rate was 91.82% and the cumulative survival rate was 97.27%. All patients were satisfied with the stability of their prostheses, and no prosthetic, peri-implant, or abutment tooth problems were observed. Telescopic tooth-implant-supported mandibular restorations with immediate loading present an alternative prosthetic solution for partially edentulous patients, providing a long-term predictable clinical outcome.


Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents.
Dengue, a mosquito-borne viral disease, was designated a World Health Organization top 10 threat to global health in 2019. We present primary efficacy data from part 1 of an ongoing phase 3 randomized trial of a tetravalent dengue vaccine candidate (TAK-003) in regions of Asia and Latin America in which the disease is endemic. Healthy children and adolescents 4 to 16 years of age were randomly assigned in a 2:1 ratio (stratified according to age category and region) to receive two doses of vaccine or placebo 3 months apart. Participants presenting with febrile illness were tested for virologically confirmed dengue by serotype-specific reverse-transcriptase polymerase chain reaction. The primary end point was overall vaccine efficacy in preventing virologically confirmed dengue caused by any dengue virus serotype. Of the 20,071 participants who were given at least one dose of vaccine or placebo (safety population), 19,021 (94.8%) received both injections and were included in the per-protocol analysis. The overall vaccine efficacy in the safety population was 80.9% (95% confidence interval [CI], 75.2 to 85.3; 78 cases per 13,380 [0.5 per 100 person-years] in the vaccine group vs. 199 cases per 6687 [2.5 per 100 person-years] in the placebo group). In the per-protocol analyses, vaccine efficacy was 80.2% (95% CI, 73.3 to 85.3; 61 cases of virologically confirmed dengue in the vaccine group vs. 149 cases in the placebo group), with 95.4% efficacy against dengue leading to hospitalization (95% CI, 88.4 to 98.2; 5 hospitalizations in the vaccine group vs. 53 hospitalizations in the placebo group). Planned exploratory analyses involving the 27.7% of the per-protocol population that was seronegative at baseline showed vaccine efficacy of 74.9% (95% CI, 57.0 to 85.4; 20 cases of virologically confirmed dengue in the vaccine group vs. 39 cases in the placebo group). Efficacy trends varied according to serotype. The incidence of serious adverse events was similar in the vaccine group and placebo group (3.1% and 3.8%, respectively). TAK-003 was efficacious against symptomatic dengue in countries in which the disease is endemic. (Funded by Takeda Vaccines; TIDES ClinicalTrials.gov number, NCT02747927.).


Updated systematic review on older adult community mobility and driver licensing policies.
An updated systematic review of literature related to the effects of driver licensing policies, community mobility programs, and driving cessation programs on older adult performance and participation was completed as a part of the American Occupational Therapy Association's Evidence-Based Literature Review Project. The results revealed that relicensing policies instituted by states yield inconsistent results in terms of reducing traffic crashes, traffic violations, and traffic-related fatalities. The evidence related to community mobility and driving cessation programs has suggested that programming to support the transition from driving to other modes of mobility can be beneficial for older adults and their family members. In addition, community contexts that are supportive of pedestrian travel significantly increase this mode of mobility. This evidence-based review informs occupational therapy practice and suggests that increased therapeutic attention should be directed toward supportive transitions from driving and sustaining community mobility for optimal engagement and participation.


Effects of long-term enalapril therapy on cardiac structure and function in patients with left ventricular dysfunction. Results of the SOLVD echocardiography substudy.
Studies of Left Ventricular Dysfunction (SOLVD) demonstrated that enalapril therapy significantly improved the clinical course of patients with left ventricular (LV) dysfunction. The goals of this substudy were to evaluate changes in LV structure and function in SOLVD patients and to test the hypothesis that enalapril inhibits remodeling in patients with LV dysfunction. Patients entering both the prevention and treatment arms of SOLVD from 5 of the 23 clinical centers were recruited for this substudy. The 301 patients who participated underwent Doppler-echocardiographic evaluation according to standard protocol before randomization to either enalapril or placebo and again after 4 and 12 months of therapy. Recorded data were analyzed in a blinded fashion at a central core laboratory. Analysis of baseline clinical characteristics showed that patients enrolled in the substudy were generally representative of the SOLVD population, although prevention arm patients were slightly overrepresented in the substudy group (69.8% compared with 61.9% of remaining SOLVD patients). The enalapril group demonstrated significant reductions in the mitral annular E-wave-to-A-wave velocity ratio (due predominantly to a reduction in E-wave velocity), and this response was different from that seen in the placebo group (P = .030). Changes in the E-to-A ratio in the enalapril group correlated significantly with changes in plasma atrial natriuretic peptide (r = .56; P < or = .01). LV end-diastolic and end-systolic volumes increased in placebo but not enalapril-treated patients, and the differences in response between the treatment groups were significant (P = .025 and .019, respectively). LV mass tended to increase in placebo patients and to be reduced in enalapril-treated patients, and the difference in response between the groups was highly significant (P < or = .001). These data demonstrate that enalapril attenuates progressive increases in LV dilatation and hypertrophy in patients with LV dysfunction. The results support the possibility that the favorable effects of enalapril reported in the SOLVD trials were related to inhibition of LV remodeling.


Does improved storage technology promote modern input use and food security? Evidence from a randomized trial in Uganda.
We use panel data from a randomized controlled trial (RCT) administered among 1200 smallholders in Uganda to evaluate input use and food security impacts of an improved maize storage technology. After two seasons, households who received the technology were 10 percentage points more likely to plant hybrid maize varieties that are more susceptible to insect pests in storage than traditional lower-yielding varieties. Treated smallholders also stored maize for a longer period, reported a substantial drop in storage losses, and were less likely to use storage chemicals than untreated cohorts. Our results indicate that policies to promote soft kernel high-yielding hybrid maize varieties in sub-Saharan Africa should consider an improvement in post-harvest storage as a complementary intervention to increase adoption of these varieties.


Management of penetrating intraperitoneal colon injuries: A meta-analysis and practice management guideline from the Eastern Association for the Surgery of Trauma.
The management of penetrating colon injuries in civilians has evolved over the last four decades. The objectives of this meta-analysis are to evaluate the current treatment regimens available for penetrating colon injuries and assess the role of anastomosis in damage control surgery to develop a practice management guideline for surgeons. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, a subcommittee of the Practice Management Guidelines section of EAST conducted a systematic review using MEDLINE and EMBASE articles from 1980 through 2017. We developed three relevant problem, intervention, comparison, and outcome (PICO) questions regarding penetrating colon injuries. Outcomes of interest included mortality and infectious abdominal complications. Thirty-seven studies were identified for analysis, of which 16 met criteria for quantitative meta-analysis and included 705 patients considered low-risk in six prospective randomized studies. Seven hundred thirty-eight patients in 10 studies undergoing damage control laparotomy and repair or resection and anastomosis (R&A) were included in a separate meta-analysis. Meta-analysis of high-risk patients undergoing repair or R&A was not feasible due to inadequate data. In adult civilian patients sustaining penetrating colon injury without signs of shock, significant hemorrhage, severe contamination, or delay to surgical intervention we recommend that colon repair or R&A be performed rather than routine colostomy. In adult high-risk civilian trauma patients sustaining penetrating colon injury, we conditionally recommend that colon repair or R&A be performed rather than routine colostomy. In adult civilian trauma patients sustaining penetrating colon injury who had damage control laparotomy, we conditionally recommend that routine colostomy not be performed; instead, definitive repair or delayed R&A or anastomosis at initial operation should be performed rather than routine colostomy. Systematic review/meta-analysis, level III.


Messenger RNA expression of target genes in the urinary sediment of patients with chronic kidney diseases.
The degree of renal scarring in kidney biopsy is an important prognostic factor in patients with chronic kidney diseases. We hypothesize that gene expression in the urinary sediment reflects the degree of renal damage. We studied 29 patients with chronic kidney disease who underwent kidney biopsy (12 immunoglobulin-A nephropathy and 17 glomerulosclerosis) and 10 healthy controls. The mRNA expressions of a panel of target genes in urinary sediment were measured by real-time quantitative polymerase chain reaction. The results were compared with the degree of histological damage and renal function decline. There were significant differences in the urinary expression of transforming growth factor-beta (TGF-beta), monocyte chemotactic protein-1 (MCP-1) and collagen IV between disease groups and controls. Urinary TGF-beta mRNA expression correlated significantly with estimated glomerular filtration rate (r = -0.412, P = 0.029) and the degree of tubulointerstitial scarring (r = 0.418, P = 0.024). Urinary MCP-1 expression correlated with the degree of glomerulosclerosis (r = 0.450, P = 0.014), but not tubulointerstitial scarring. Urinary MCP-1 expression correlated with its corresponding level by enzyme-linked immunosorbent assay (ELISA) (r = 0.650, P<0.001), but TGF-beta expression did not correlate with its ELISA level. Urinary TGF-beta gene expression correlated with its intra-renal expression in glomeruli (r = 0.701, P<0.001) and tubulointerstitium (r = 0.573, P = 0.001) by immunohistochemistry, while urinary MCP-1 gene expression correlated with its staining in glomeruli (r = 0.576, P = 0.001) but not tubulointerstitium. After 12 months, there was a significant inverse correlation between the rate of renal function decline and urinary expression of connective tissue growth factor (r = -0.471, P = 0.010) and collagen I (r = -0.399, P = 0.032), but not TGF-beta or MCP-1. Amongst the target genes examined, the mRNA expression of TGF-beta in urinary sediment correlated with renal function, the degree of histological damage and intra-renal level in patients with chronic kidney diseases. Measurement of TGF-beta mRNA expression in urine may be a useful non-invasive tool for assessing the severity of renal damage in patients with chronic kidney diseases.


Monochlorinated calocerins A-D and 9-oxostrobilurin derivatives from the basidiomycete Favolaschia calocera.
Eight previously undescribed compounds were isolated and characterised from the supernatant and mycelium of a culture of the basidiomycete Favolaschia calocera originating from Kakamega equatorial rainforest in Kenya. These were: 9- oxostrobilurins A, G, K and I and the four monochlorinated calocerins A, B, C and D. The calocerins extend our knowledge of halogenated compounds obtained from natural sources. Four further known compounds were also identified: strobilurin G, favolon, pterulinic acid and 2,3 -dihydro-1-benzoxepin derivative. The four oxostrobilurins exhibited prominent antifungal and cytotoxic activities while the four calocerins only showed cytotoxic activity.


Osteomyelitis in cold-stunned Kemp's ridley sea turtles (Lepidochelys kempii) hospitalized for rehabilitation: 25 cases (2008-2018).
To characterize osteolytic lesions in cold-stunned Kemp's ridley sea turtles (Lepidochelys kempii) hospitalized for rehabilitation and describe methods used for the management of such lesions. 25 stranded, cold-stunned Kemp's ridley sea turtles hospitalized between 2008 and 2018. Medical records of sea turtles with a diagnosis of osteolytic lesions were reviewed retrospectively to obtain the date of diagnosis, clinical signs, radiographic findings, microbial culture results, hematologic and plasma biochemical data, cytologic and histologic findings, antimicrobial history, time to first negative culture result, treatment duration, and outcome. Lesions were identified radiographically a median of 50 days after admission and were located within epiphyses or metaphyses of various appendicular joints. Lesions were associated with periarticular swelling (n = 24), lameness (16), lethargy (2), and hyporexia (2). Bacterial culture yielded growth of single organisms (n = 16), multiple organisms (2), or no growth (6). Significant differences in hematologic and biochemical data were detected between the times of diagnosis and convalescence. Cytologic and histologic findings characterized the lesions as osteomyelitis leading to septic arthritis. Sixteen sea turtles were managed medically, and 8 were managed medically and surgically. Surgery resulted in rapid improvement in joint mobility and overall clinical status. Most (22/25 [88%]) sea turtles survived and were released after long-term management. During rehabilitation, cold-stunned Kemp's ridley sea turtles may be affected by osteomyelitis. Medical management based on antimicrobial susceptibility testing was effective for most turtles. Long term management efforts in turtles are justified by high survival rate.


beta-Adrenergic stimulation promotes homocysteic acid release from astrocyte cultures: evidence for a role of astrocytes in the modulation of synaptic transmission.
The sulfur-containing amino acid homocysteic acid (HCA) is present in and released from nervous tissue, exerting excitatory effects on neurons by predominantly activating NMDA receptors. It is interesting that HCA appears to be exclusively localized in glial cells, not in neurons. This profile of glial localization and excitatory action on neurons has led to the hypothesis that HCA could participate in intercellular communication in the brain as a "gliotransmitter." To test this hypothesis further, we searched for specific, receptor-mediated stimuli that could induce release of HCA from cultured astrocytes. For this reason we tested the effect of noradrenaline and vasoactive intestinal peptide, two transmitters known to interact with specific receptors on astrocytes, on the release of HCA from these cells. Noradrenaline and the beta-adrenergic agonist isoproterenol induced an efflux of HCA from astrocyte cultures. Further stressing the beta-adrenergic mediation of this effect is the blockade by atenolol of the HCA release evoked by isoproterenol. The stimulation of HCA release from astrocytes was not observed with the alpha-noradrenergic agonist methoxamine and with vasoactive intestinal peptide. These results taken together further strengthen the role of HCA as a gliotransmitter. Its efflux from glia could be controlled by noradrenaline, activating beta-adrenergic receptors on astrocytes. The present study provides the first evidence for an influence of beta-adrenergic receptor activation on the release of an excitatory amino acid from astrocytes and further supports the notion that glial-neuronal interactions play a role in synaptic transmission.


Herpesvirus tamarinus and its relation to herpes simplex virus.
We have characterized Herpesvirus tamarinus (HT), a virus of New World primates related to herpes simplex virus. HT virion DNA cross-hybridized appreciably with herpes simplex virus type 1 (HSV-1) DNA. The HT-HSV-1 cross-hybridizing DNA sequences were distributed over the length of the genome; some DNA sequences, however, were apparently more homologous than others. HT virion DNA was estimated from the sum of restriction endonuclease fragments to have a mol. wt. 98 X 10(6). Only 1 molar fragments were found with some restriction endonucleases and 0.5 and 1 molar fragments were found with other restriction endonucleases but no evidence was found for 0.25 molar fragments. Independent isolates of HT from different species of South American primates gave nearly identical restriction endonuclease cleavage patterns of virion DNA. Although cross-reacting antigenic proteins of HT and HSV-1 were not detected by neutralization or immunofluorescence tests, cross-reacting antigenic proteins were detected by SDS-polyacrylamide gel electrophoresis of immunoprecipitates of 35S-labelled infected cell extracts.


Should we transport coal, gas, or electricity: cost, efficiency, and environmental implications.
We examine the life cycle costs, environmental discharges, and deaths of moving coal via rail, coal gas via pipeline, and electricity via wire from the Powder River Basin (PRB) in Wyoming to Texas. Which method has least social cost depends on how much additional investment in rail line, transmission, or pipeline infrastructure is required, as well as how much and how far energy is transported. If the existing rail lines have unused capacity, coal by rail is the cheapest method (up to 200 miles of additional track could be added). If no infrastructure exists, greater distances and larger amounts of energy favor coal by rail and gasified coal by pipeline over electricity transmission. For 1,000 miles and 9 gigawatts of power, a gas pipeline is cheapest, has less environmental discharges, uses less land, and is least obtrusive.


Ultra-High Packing Density Next Generation Microtube Array Membrane for Absorption Based Applications.
Previously, we successfully developed an extracorporeal endotoxin removal device (EERD) that is based on the novel next generation alternating microtube array membrane (MTAM-A) that was superior to the commercial equivalent. In this article, we demonstrated multiple different parameter modifications that led to multiple different types of novel new MTAM structures, which ultimately led to the formation of the MTAM-A. Contrary to the single layered MTAM, the MTAM-A series consisted of a superior packing density fiber connected in a double layered, alternating position which allowed for the greater fiber count to be packed per unit area. The respective MTAM variants were electrospun by utilizing our internally developed tri-axial electrospinning set up to produce the novel microstructures as seen in the respective MTAM variants. A key uniqueness of this study is the ability to produce self-arranged fibers into the respective MTAM variants by utilizing a single spinneret, which has not been demonstrated before. Of the MTAM variants, we observed a change in the microstructure from a single layered MTAM to the MTAM-A series when the ratio of surfactant to shell flow rate approaches 1:1.92. MTAM-A registered the greatest surface area of 2.2 times compared to the traditional single layered MTAM, with the greatest tensile strength at 1.02 ± 0.13 MPa and a maximum elongation of 57.70 ± 9.42%. The MTAM-A was selected for downstream immobilization of polymyxin B (PMB) and assembly into our own internally developed and fabricated dialyzer housing. Subsequently, the entire setup was tested with whole blood spiked with endotoxin; and benchmarked against commercial Toraymyxin fibers of the same size. The results demonstrated that the EERD based on the MTAM-A performed superior to that of the commercial equivalent, registering a rapid reduction of 73.18% of endotoxin (vs. Toraymyxin at 38.78%) at time point 15 min and a final total endotoxin removal of 89.43% (vs. Toraymyxin at 65.03%).


Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia.
Some patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop severe pneumonia and acute respiratory distress syndrome1 (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from that in other types of pneumonia2. Here we investigate SARS-CoV-2 pathobiology by characterizing the immune response in the alveoli of patients infected with the virus. We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens, and analysed them using flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA sequencing on 10 bronchoalveolar lavage fluid samples collected from patients with severe coronavirus disease 2019 (COVID-19) within 48 h of intubation. In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. These T cells produce interferon-γ to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. Collectively, our results suggest that SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis in which alveolar macrophages containing SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.


Coping in stressful episodes: the role of individual differences, environmental factors, and situational characteristics.
Theoretical models emphasize the importance of person and environmental variables in stress and coping processes. This article examines individual differences (extraversion and neuroticism), environmental factors (social support and work demand), and situational characteristics (type of stressful episode and its perceived importance) as predictors of three self-report measures of coping (general coping, direct coping, and suppression) derived from the Ways of Coping Questionnaire. The data analyzed were collected from 135 first-year female student nurses. Individual differences were assessed prior to exposure to the ward environment, and information about stressful episodes was obtained during the initial period of nursing practice. Multiple regression analyses showed that individual differences and environmental and situational factors were significant predictors of the coping scores and that patterns of main and interactive effects were different for each type of coping. For direct coping and suppression, predicted interactions across person, environmental, and situational variables contributed significantly to the explained variance. Curvilinear interactions between work demand and neuroticism were significant for both direct coping and suppression; interactions of social support and extraversion with perceived importance predicted direct coping; and interactions between neuroticism and extraversion and between work demand and importance predicted suppression. These findings are discussed in relation to current substantive and methodological issues in the study of coping and adaptation.


Single-pass and omniangle light extraction from light-emitting diodes using transformation optics.
We present a light-extraction approach allowing for single-pass and omniangle outcoupling of light from light-emitting diodes (LED). By using transformation optics, we perceive a feasible graded-index structure that is a transition from the LED exit facet to a low refractive index region with expanded space that represents air. Apart from the material dispersion of the constituents, our approach is wavelength independent. The suggested extractor is geometrically compact with size parameters comparable to the width of an LED and therefore well adapted for pixelated LEDs. A beam-expanding functionality is possible while fully preserving the outcoupling efficiency by applying index and geometry truncation.


Effect of CCN2 on FGF2-induced proliferation and MMP9 and MMP13 productions by chondrocytes.
CCN2 (also known as connective tissue growth factor) interacts with several growth factors involved in endochondral ossification via its characteristic four modules and modifies the effect of such growth factors. Presently we investigated whether CCN2 interacts with fibroblast growth factor 2 (FGF2). Solid-phase binding assay, immunoprecipitation-Western blot analysis, and surface plasmon resonance (SPR) spectroscopy revealed that the C-terminal module of CCN2 (CT) directly bound to FGF2 with a dissociation constant of 5.5 nm. Next, we examined the combinational effects of CCN2 and FGF2 on the proliferation of and matrix metalloproteinase (MMP)-9 and -13 productions by cultured chondrocytes. FGF2 promoted not only the proliferation but also the production of MMP9 and -13, however, combined of FGF2 with CT module nullified the enhancement of both MMP productions and proliferation. To clarify the mechanism, we investigated the binding of CCN2 or its CT module to FGF receptor 1. As a result, we found that CCN2 bound to FGF receptor 1 with a dissociation constant of 362 nm, whereas the CT module did not. In addition, when we tested FGF signaling in chondrocytic HCS-2/8 cells stimulated by the combination of FGF2 with CT module, the level of ERK1/2, p38 MAPK, and c-Jun N-terminal kinase phosphorylation was decreased compared with that found with FGF2 alone. These findings suggest that CCN2 may regulate the proliferation and matrix degradation of chondrocytes by forming a complex with FGF2 as a novel modulator of FGF2 functions.


180° Ferroelectric Stripe Nanodomains in BiFeO3 Thin Films.
There is growing evidence that domain walls in ferroics can possess emergent properties that are absent in the bulk. For example, 180° ferroelectric domain walls in the ferroelectric-antiferromagnetic BiFeO3 are particularly interesting because they have been predicted to possess a range of intriguing behaviors, including electronic conduction and enhanced magnetization. To date, however, ordered arrays of such domain structures have not been reported. Here, we report the observation of 180° stripe nanodomains in (110)-oriented BiFeO3 thin films grown on orthorhombic GdScO3 (010)O substrates and their impact on exchange coupling to metallic ferromagnets. Nanoscale ferroelectric 180° stripe domains with {112̅} domain walls were observed in films <32 nm thick. With increasing film thickness, we observed a domain structure crossover from the depolarization field-driven 180° stripe nanodomains to 71° ferroelastic domains determined by the elastic energy. These 180° domain walls (which are typically cylindrical or meandering in nature due to a lack of strong anisotropy associated with the energy of such walls) are found to be highly ordered. Additional studies of Co0.9Fe0.1/BiFeO3 heterostructures reveal exchange bias and exchange enhancement in heterostructures based on BiFeO3 with 180° domain walls and an absence of exchange bias in heterostructures based on BiFeO3 with 71° domain walls; suggesting that the 180° domain walls could be the possible source for pinned uncompensated spins that give rise to exchange bias. This is further confirmed by X-ray circular magnetic dichroism studies, which demonstrate that films with predominantly 180° domain walls have larger magnetization than those with primarily 71° domain walls. Our results could be useful to extract the structure of domain walls and to explore domain wall functionalities in BiFeO3.


A single-blinded, randomized pilot study evaluating effects of electroacupuncture in diabetic patients with symptoms suggestive of gastroparesis.
The current pharmacological management of diabetic gastroparesis remains difficult. Acupuncture has been widely used for gastrointestinal symptoms. The aim of this study was to investigate the effects of electroacupuncture (EA) on solid gastric emptying time, serum gastrin, motilin, pancreatic polypeptide (PP), fasting and postprandial blood glucose, and symptoms in patients with diabetic gastroparesis. EA at the Zusanli (ST 36) and Hegu (LI 4) points and sham EA as control were administered by an experienced and licensed acupuncturist. This was a pilot study with a randomized, single-blinded design. Nineteen (19) patients with type 2 diabetes who had had symptoms of gastroparesis for more than 3 months were included in the trial and randomized into two groups. Each group received EA (n = 9) or sham EA (n = 10) consisting of 4 sessions over 2 weeks. Symptom severity was evaluated using the Gastroparesis Cardinal Symptom Index (GCSI) at baseline, at the end of treatment, and 2 weeks after the end of the trial; solid-phase gastric half-emptying time was measured by scintigraphy; in addition, serum gastrin, motilin, PP, fasting, and postprandial blood glucose levels were also measured. Gastric half-emptying time in 9 patients with diabetic gastroparesis was significantly shortened by EA treatment (143.8 +/- 55.9 minutes versus 98.8 +/- 28.6 minutes, p < 0.03). Half-emptying time did not change (98.9 +/- 26.4 minutes versus 90.9 +/- 24.8 minutes, p > 0.05) in the sham EA group. Symptom severity, as measured by GCSI total score, improved significantly both at the end of treatment (2.38 +/- 0.56 versus 1.48 +/- 0.19, p < 0.001) and 2 weeks after the end of the trial (2.38 +/- 0.56 versus 1.65 +/- 0.44, p < 0.01) when compared with the baseline in the EA group, but did not change from baseline with sham EA treatment. There were no significant changes in fasting and postprandial blood glucose, serum gastrin, motilin, and PP in both groups. No significant adverse events occurred. This study demonstrates that short-term EA at the Zusanli and Hegu points effectively reduces the dyspeptic symptoms of diabetic gastroparesis and accelerates solid gastric emptying. Sustained improvement in dyspeptic symptoms was observed at 2 weeks after the end of the trial. Its potential for treating gastroparesis may be explored, and a larger trial is required to draw definitive conclusions.


Ral GTPases regulate exocyst assembly through dual subunit interactions.
Ral GTPases have been implicated in the regulation of a variety of dynamic cellular processes including proliferation, oncogenic transformation, actin-cytoskeletal dynamics, endocytosis, and exocytosis. Recently the Sec6/8 complex, or exocyst, a multisubunit complex facilitating post-Golgi targeting of distinct subclasses of secretory vesicles, has been identified as a bona fide Ral effector complex. Ral GTPases regulate exocyst-dependent vesicle trafficking and are required for exocyst complex assembly. Sec5, a membrane-associated exocyst subunit, has been identified as a direct target of activated Ral; however, the mechanism by which Ral can modulate exocyst assembly is unknown. Here we report that an additional component of the exocyst, Exo84, is a direct target of activated Ral. We provide evidence that mammalian exocyst components are present as distinct subcomplexes on vesicles and the plasma membrane and that Ral GTPases regulate the assembly interface of a full octameric exocyst complex through interaction with Sec5 and Exo84.


Dry eye: prevalence and attributable risk factors in a hospital-based population.
To study the prevalence of dry eye in a hospital-based population and to evaluate the various risk factors attributable to dry eye. In this cross-sectional study, 500 patients above 20 years of age were screened randomly for dry eye. A 13-point questionnaire, Lissamine Green test, Tear film break-up time (TBUT), Schirmer's test and presence of strands/filaments were used to diagnose dry eye. The diagnosis was made when at least three of the tests were positive. The role of air pollution, sunlight, excessive winds, smoking, drugs and refractive status as dry eye risk factors was assessed. Ninety-two (18.4%) patients had dry eye. Dry eye prevalence was maximum in those above 70 years of age (36.1%) followed by the age group 31-40 years (20%). It was significantly higher (P = 0.024) in females (22.8%) than in males (14.9%), more common in rural residents (19.6%) than in urban (17.5%) and highest among farmers/labourers (25.3%). A 2.15 fold increase was found in the odds for dry eye in those exposed to excessive wind, 1.91 fold to sunlight exposure, 1.42 to smoking, 1.38 to air pollution and 2.04 for persons on drugs. Dry eye prevalence was 14% in emmetropes, 16.8% in myopes and 22.9% in hypermetropes. It was 15.6% in those with corrected and 25.3% in those with uncorrected refractive errors. Dry eye is an under-diagnosed ocular disorder. Reduction in the modifiable risk factors of dry eye is essential to reduce its prevalence.


A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes.
We performed a multitiered, case-control association study of psoriasis in three independent sample sets of white North American individuals (1,446 cases and 1,432 controls) with 25,215 genecentric single-nucleotide polymorphisms (SNPs) and found a highly significant association with an IL12B 3'-untranslated-region SNP (rs3212227), confirming the results of a small Japanese study. This SNP was significant in all three sample sets (odds ratio [OR](common) 0.64, combined P [Pcomb]=7.85x10(-10)). A Monte Carlo simulation to address multiple testing suggests that this association is not a type I error. The coding regions of IL12B were resequenced in 96 individuals with psoriasis, and 30 additional IL12B-region SNPs were genotyped. Haplotypes were estimated, and genotype-conditioned analyses identified a second risk allele (rs6887695) located approximately 60 kb upstream of the IL12B coding region that exhibited association with psoriasis after adjustment for rs3212227. Together, these two SNPs mark a common IL12B risk haplotype (OR(common) 1.40, Pcomb=8.11x10(-9)) and a less frequent protective haplotype (OR(common) 0.58, Pcomb=5.65x10(-12)), which were statistically significant in all three studies. Since IL12B encodes the common IL-12p40 subunit of IL-12 and IL-23, we individually genotyped 17 SNPs in the genes encoding the other chains of these cytokines (IL12A and IL23A) and their receptors (IL12RB1, IL12RB2, and IL23R). Haplotype analyses identified two IL23R missense SNPs that together mark a common psoriasis-associated haplotype in all three studies (OR(common) 1.44, Pcomb=3.13x10(-6)). Individuals homozygous for both the IL12B and the IL23R predisposing haplotypes have an increased risk of disease (OR(common) 1.66, Pcomb=1.33x10(-8)). These data, and the previous observation that administration of an antibody specific for the IL-12p40 subunit to patients with psoriasis is highly efficacious, suggest that these genes play a fundamental role in psoriasis pathogenesis.


Understanding the day-to-day lives of obese children and their families.
This study investigated the daily lives of obese children and their families to better understand factors influencing weight-related behaviors. A multiple case study design was implemented with 6 obese children and their families. Participant observations occurred in different settings from when the children woke until they went to bed, yielding approximately 95 hours of data per family. Lack of parenting skills and role modeling, environments encouraging poor weight-related behaviors, low self-awareness and enjoyment of sedentary activities were common themes. Child obesity involves a complex set of factors interacting to place a child at risk of developing weight problems.


Comparison of upper airway collapse patterns and its clinical significance: drug-induced sleep endoscopy in patients without obstructive sleep apnea, positional and non-positional obstructive sleep apnea.
To compare patient characteristics, upper airway (UA) collapse patterns and treatment outcome in obstructive sleep apnea (OSA) patients, including non-positional OSA patients (NPP) and positional OSA patients (PP), and non-OSA. Cohort study of patients screened for OSA in 2012. Polysomnography was performed and UA was evaluated using the VOTE classification during drug-induced sleep endoscopy (DISE). Treatment outcome of MAD and UA surgery was evaluated. Eight hundred sixty patients were included. Higher BMI, larger neck circumference, and greater age were independent significant predictors for OSA. DISE was performed in 543 patients: 119 non-OSA and 424 OSA patients of whom 257 PP and 167 NPP patients. PP were younger, had smaller neck circumference, lower BMI and apnea-hypopnea index (AHI) than NPP. Collapse at velum (p < 0.001) and oropharynx (p < 0.001) significantly increased the odds for having OSA. Tongue base and epiglottis collapse were, on group level, not determinative for OSA or non-OSA. Complete concentric collapse (CCC) was observed less frequently in PP (31.5%) as compared to NPP (46.1%). After UA surgery, OSA often was cured or improved to less severe positional OSA. Lower efficacy of UA surgery was observed in PP as compared to NPP. No differences were observed in MAD treatment outcome. Current study provides insight in patients screened for OSA: collapse at velum and oropharynx significantly determined presence of OSA and CCC occurred less frequently in PP compared to NPP. In addition, residual positional dependency is common after UA surgery. More trials are needed to gain insight in pathophysiology and treatment outcome.


Tumor promoter-induced refractory state against ornithine decarboxylase induction by 12-O-tetradecanoylphorbol-13-acetate in mouse epidermis.
More than one application of the potent tumor-promoting agent, 12-O-tetradecanoylphorbol-13-acetate (TPA), to mouse skin at intervals of more than 48 h led to a larger induction of ornithine decarboxylase (EC 22.214.171.124; ODC) than did a single application. In contrast, at intervals of less than 24 h, the first application of TPA appeared to induce a refractory state; the second application of TPA did not induce ODC. The extent of the inhibitory effect caused by the first application of TPA was dependent on the dose. The abilities of a series of phorbol esters to induce the refractory state correlated with their promoting abilities. However, both mezerein and ethylphenylpropiolate, potent hyperplastic agents with little or no promoting properties, induced the refractory state. On the other hand, pretreatment with TPA caused a refractory effect on ODC induction by mezerein but potentiated ODC induction by ethylphenylpropiolate. The epidermal cells escaped from the refractory state by repeated application of TPA at intervals of 24 h as well as at intervals of twice a week; that is, there was a full induction of ODC activity following a second application within 24 h of a prior application. TPA did not elicit production of detectable ODC-antizyme activity in mouse epidermis. Mixing of a soluble extract from mouse epidermis in the refractory state with that from TPA-stimulated epidermis gave essentially additive ODC activity. Elimination of ODC induction by topical application of retinoic acid or injection of cycloheximide concurrent with the first application of TPA did not restore the ability of a second application of TPA to induce ODC. These results suggest that the refractory effect on ODC induction by TPA does not result from feedback regulation of ODC.


Clinical aspects of the link between chronic sinonasal diseases and asthma.
Chronic sinonasal diseases (CSDs) are common comorbidity of asthma. The aim of this study was to assess comprehensively CSD in a population of asthma patients and determine whether the clinical factors in both diseases were related to each other. Eighty adult stable asthmatic patients with sinonasal symptoms (SNSs) of 3 months and who were nonresponsive to aggressive medical treatment were prospectively investigated. All patients underwent a detailed ear, nose, and throat examination and were evaluated by paranasal sinus computed tomography (PNS-CT). The severity of asthma was compared with SNS scores (SNSSs) and sinonasal involvement on PNS-CT. Asthma was severe in 12.5%, moderate in 55%, and mild in 32.5% of cases. There were 15 (18.7%) patients in stage 0, 16 (20%) patients in stage 1, 21 (26.2%) patients in stage 2, and 28 (35%) patients in stage 3 according to PNS-CT scoring. There was no correlation between asthma severity and CT stages, total opacification scores (TOSs), anatomic variations, and SNSSs. Although SNSSs were similar in patients with nasal polyps (NPs) and without NPs, patients with NPs showed significantly higher TOSs and CT stages (p < 0.05). The presence of NPs and age and duration of disease were related to severity of asthma (p < 0.05). Nonatopic asthmatic patients had both more severe asthma (p = 0.05) and more extensive CT findings (p = 0.01). The use of clinical symptoms alone is not very reliable in predicting the presence or severity of CSD. Therefore, SNSs should be supported with objective criteria such as nasal endoscopy and PNS-CT scan. Furthermore, sinonasal involvement may exist independently from severity of asthma.


Establishing a reference group for distal 18q-: clinical description and molecular basis.
Although constitutional chromosome abnormalities have been recognized since the 1960s, clinical characterization and development of treatment options have been hampered by their obvious genetic complexity and relative rarity. Additionally, deletions of 18q are particularly heterogeneous, with no two people having the same breakpoints. We identified 16 individuals with deletions that, despite unique breakpoints, encompass the same set of genes within a 17.6-Mb region. This group represents the most genotypically similar group yet identified with distal 18q deletions. As the deletion is of average size when compared with other 18q deletions, this group can serve as a reference point for the clinical and molecular description of this condition. We performed a thorough medical record review as well as a series of clinical evaluations on 14 of the 16 individuals. Common functional findings included developmental delays, hypotonia, growth hormone deficiency, and hearing loss. Structural anomalies included foot anomalies, ear canal atresia/stenosis, and hypospadias. The majority of individuals performed within the low normal range of cognitive ability but had more serious deficits in adaptive abilities. Of interest, the hemizygous region contains 38 known genes, 26 of which are sufficiently understood to tentatively determine dosage sensitivity. Published data suggest that 20 are unlikely to cause an abnormal phenotype in the hemizygous state and five are likely to be dosage sensitive: TNX3, NETO1, ZNF407, TSHZ1, and NFATC. A sixth gene, ATP9B, may be conditionally dosage sensitive. Not all distal 18q- phenotypes can be attributed to these six genes; however, this is an important advance in the molecular characterization of 18q deletions.


Patella alta and chondromalacia.
The Insall-Salvati method of determining the position of the patella by radiography was employed in fifty-one patients with chondromalacia patellae that had been proved at arthrotomy. There was no definite relationship between chondromalacia patellae and patella alta. There was, however, a highly significant statistical difference between the ratio of the length of the patella to that of the patellar tendon in normal men and women.


Meta-Analysis of Usefulness of Psyllium Fiber as Adjuvant Antilipid Therapy to Enhance Cholesterol Lowering Efficacy of Statins.
Statins are usually well-tolerated drugs with a clear dose-dependent efficacy. However, manifestation of statin's side effects also bears a direct relation to higher doses necessary to achieve high impact cholesterol-lowering effects. Nevertheless, the reliance on statin efficacy alone has often left dietary intervention underutilized even though studies have shown a reduction in serum cholesterol levels when dietary fiber intake is increased. In this meta-analysis, we investigated whether the concomitant use of psyllium, a gel-forming viscous soluble fiber, would cause further overall cholesterol lowering in subjects already receiving statins. A systematic review of the medical literature was performed and identified three randomized, controlled clinical studies that evaluated the cholesterol lowering efficacy of statins when given concomitantly with psyllium as a fiber supplement. The duration of the studies ranged from 4 weeks to 12 weeks. The objective of the meta-analysis was to estimate the overall effect of psyllium plus statin versus statin alone. The results of the meta-analysis showed a clinically and statistically significant (p = 0.001) cholesterol lowering advantage for psyllium plus statin combination treatment over a statin alone. Adding psyllium fiber resulted in reductions in low-density lipoprotein-cholesterol equivalent to doubling the statin dose. In conclusion, the data support that psyllium fiber takenbefore meals adds to the efficacy of statins, providing an easy to implement dietary intervention for those who cannot tolerate side effects associated with higher-dose statins.


How to reduce sitting time? A review of behaviour change strategies used in sedentary behaviour reduction interventions among adults.
Sedentary behaviour - i.e., low energy-expending waking behaviour while seated or lying down - is a health risk factor, even when controlling for physical activity. This review sought to describe the behaviour change strategies used within interventions that have sought to reduce sedentary behaviour in adults. Studies were identified through existing literature reviews, a systematic database search, and hand-searches of eligible papers. Interventions were categorised as 'very promising', 'quite promising', or 'non-promising' according to observed behaviour changes. Intervention functions and behaviour change techniques were compared across promising and non-promising interventions. Twenty-six eligible studies reported thirty-eight interventions, of which twenty (53%) were worksite-based. Fifteen interventions (39%) were very promising, eight quite promising (21%), and fifteen non-promising (39%). Very or quite promising interventions tended to have targeted sedentary behaviour instead of physical activity. Interventions based on environmental restructuring, persuasion, or education were most promising. Self-monitoring, problem solving, and restructuring the social or physical environment were particularly promising behaviour change techniques. Future sedentary reduction interventions might most fruitfully incorporate environmental modification and self-regulatory skills training. The evidence base is, however, weakened by low-quality evaluation methods; more RCTs, employing no-treatment control groups, and collecting objective data are needed.


Progenitor cells as remote "bioreactors": neuroprotection via modulation of the systemic inflammatory response.
Acute central nervous system (CNS) injuries such as spinal cord injury, traumatic brain injury, autoimmune encephalomyelitis, and ischemic stroke are associated with significant morbidity, mortality, and health care costs worldwide. Preliminary research has shown potential neuroprotection associated with adult tissue derived stem/progenitor cell based therapies. While initial research indicated that engraftment and transdifferentiation into neural cells could explain the observed benefit, the exact mechanism remains controversial. A second hypothesis details localized stem/progenitor cell engraftment with alteration of the loco-regional milieu; however, the limited rate of cell engraftment makes this theory less likely. There is a growing amount of preclinical data supporting the idea that, after intravenous injection, stem/progenitor cells interact with immunologic cells located in organ systems distant to the CNS, thereby altering the systemic immunologic/inflammatory response. Such distant cell "bioreactors" could modulate the observed post-injury pro-inflammatory environment and lead to neuroprotection. In this review, we discuss the current literature detailing the above mechanisms of action for adult stem/progenitor cell based therapies in the CNS.


[Bone metabolism in child and adolescent athletes: a systematic review].
Physical exercise is beneficial for the prevention of osteoporosis. Bone metabolism markers are the main indicators of metabolic balance and may indicate early risk in bone tissue. This systematic review aims to summarize and update present knowledge about bone metabolism markers in child and adolescent athletes. Literature search was conducted up to March 2017 in PubMed and Sport Discus. A total of 19 studies (case-control, longitudinal and randomized control trials) met the inclusion criteria and were included in the review. In females, bone remodeling decreases with age independently of sport practiced. Athletes with amenorrhea had lower levels of both markers of bone turnover than control subjects. High-impact sports present higher biomarkers in females. A brief period of training have positive effects in bone formation markers in adolescent males. The age, sex type of exercise and sport, and performance level of the subjects can deeply affect bone metabolism markers during adolescence. More studies are needed to establish common criteria for metabolic response to physical exercise in these stages.


Serum IgE reactivity profiling in an asthma affected cohort.
Epidemiological evidence indicates that atopic asthma correlates with high serum IgE levels though the contribution of allergen specific IgE to the pathogenesis and the severity of the disease is still unclear. We developed a microarray immunoassay containing 103 allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals belonging to families whose members have a documented history of asthma and atopy. We employed k-means clustering, to investigate whether a particular IgE reactivity profile correlated with asthma and other atopic conditions such as rhinitis, conjunctivitis and eczema. Both case-control and parent-to-siblings analyses demonstrated that while the presence of specific IgE against individual allergens correlated poorly with pathological conditions, particular reactivity profiles were significantly associated with asthma (p<10E-09). An artificial neural network (ANN)-based algorithm, calibrated with the profile reactivity data, correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Multivariate statistical analysis demonstrated that the familiar relationships of the study population did not affect the observed correlations. These findings indicate that asthma is a higher-order phenomenon related to patterns of IgE reactivity rather than to single antibody reactions. This notion sheds new light on the pathogenesis of the disease and can be readily employed to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile.


Somatic and axonal LIGHT signaling elicit degenerative and regenerative responses in motoneurons, respectively.
A receptor-ligand interaction can evoke a broad range of biological activities in different cell types depending on receptor identity and cell type-specific post-receptor signaling intermediates. Here, we show that the TNF family member LIGHT, known to act as a death-triggering factor in motoneurons through LT-βR, can also promote axon outgrowth and branching in motoneurons through the same receptor. LIGHT-induced axonal elongation and branching require ERK and caspase-9 pathways. This distinct response involves a compartment-specific activation of LIGHT signals, with somatic activation-inducing death, while axonal stimulation promotes axon elongation and branching in motoneurons. Following peripheral nerve damage, LIGHT increases at the lesion site through expression by invading B lymphocytes, and genetic deletion of Light significantly delays functional recovery. We propose that a central and peripheral activation of the LIGHT pathway elicits different functional responses in motoneurons.


[Indications for the evaluation of reproductive health and pertinent programs].
This report presents a set of indicators to aid in the assessment of reproductive health and its associated programs in developing countries. The indicators basically stem from the accords ratified at the International Conference on Population and Development (ICPD), which was held in 1994 for the purpose of improving the reproductive health status of women, men, and adolescents throughout the world. However, working drafts and ways of approaching the subject were developed in 1996 at several meetings of representatives of the United Nations Population Fund (UNFPA), bilateral agencies, and nongovernmental organizations. The indicators are not in their definitive and final form, and it is expected that comments received from users will allow them to be improved. The indicators deal with the monitoring of progress toward the goals of the ICPD, managerial policies and procedures, family planning, maternal health, infections of the reproductive system and sexually transmitted diseases, abortion and infertility, and other demographic, social, and economic factors.


The coming of age of chaperone-mediated autophagy.
Chaperone-mediated autophagy (CMA) was the first studied process that indicated that degradation of intracellular components by the lysosome can be selective - a concept that is now well accepted for other forms of autophagy. Lysosomes can degrade cellular cytosol in a nonspecific manner but can also discriminate what to target for degradation with the involvement of a degradation tag, a chaperone and a sophisticated mechanism to make the selected proteins cross the lysosomal membrane through a dedicated translocation complex. Recent studies modulating CMA activity in vivo using transgenic mouse models have demonstrated that selectivity confers on CMA the ability to participate in the regulation of multiple cellular functions. Timely degradation of specific cellular proteins by CMA modulates, for example, glucose and lipid metabolism, DNA repair, cellular reprograming and the cellular response to stress. These findings expand the physiological relevance of CMA beyond its originally identified role in protein quality control and reveal that CMA failure with age may aggravate diseases, such as ageing-associated neurodegeneration and cancer.


Complete genome sequence of Leadbetterella byssophila type strain (4M15).
Leadbetterella byssophila Weon et al. 2005 is the type species of the genus Leadbetterella of the family Cytophagaceae in the phylum Bacteroidetes. Members of the phylum Bacteroidetes are widely distributed in nature, especially in aquatic environments. They are of special interest for their ability to degrade complex biopolymers. L. byssophila occupies a rather isolated position in the tree of life and is characterized by its ability to hydrolyze starch and gelatine, but not agar, cellulose or chitin. Here we describe the features of this organism, together with the complete genome sequence, and annotation. L. byssophila is already the 16(th) member of the family Cytophagaceae whose genome has been sequenced. The 4,059,653 bp long single replicon genome with its 3,613 protein-coding and 53 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project.


Risk factors for and assessment of symptomatic pseudarthrosis after lumbar pedicle subtraction osteotomy in adult spinal deformity.
Retrospective review of prospectively collected data. To assess the prevalence, risk factors, and clinical outcomes for pseudarthrosis after a lumbar pedicle subtraction osteotomy (PSO). There exists no large series that examines pseudarthrosis rates of PSOs. Data of 171 consecutive patients with adult deformity who underwent a lumbar PSO by 2 surgeons at a single institution with a minimum 2-year follow-up were analyzed. Pseudarthrosis diagnosed through sagittal malalignment and instrumentation failure noted on radiograph was confirmed intraoperatively. Eighteen (10.5%) of 171 patients developed pseudarthrosis after a PSO. Eleven of the 18 patients (6.4% of all patients, 61.1% of the 18 patients with pseudarthrosis) had pseudarthrosis at the PSO site, L3 being the most common; other locations included the lumbosacral junction (4/18), thoracolumbar junction (2/18), and upper thoracic spine (1/18). Preoperative pseudarthrosis level was a predictor of the postoperative level of pseudarthrosis (93%). Fifteen of the 18 patients (83%) had no interbody fusion directly above or below the PSO site, 16 (88%) had a history of pseudarthrosis at the time of PSO surgery and 2 of 3 patients who had prior radiation to the lumbar region developed pseudarthrosis. Most pseudarthroses occurred within the first 2 years (n = 13/18), between 2 and 5 years (n = 3/18), and more than 5 years (n = 2/18) postoperatively. Prior pseudarthrosis (P < 0.0001), pseudarthrosis at the PSO site (P < 0.0001), prior decompression in the lumbar region (P = 0.0037), prior radiation to the lumbar region (P < 0.0001), and presence of inflammatory/neurological disorders (P < 0.0036) were identified as risk factors. All 18 patients with pseudarthroses required revision surgery (posterior-only surgery, n = 12; anteroposterior surgery, n = 6) due to loss of sagittal alignment and pain. The mean pre-revision Scoliosis Research Society score was 85, post-revision score was 95 (P = 0.0166), and the mean pre-revision Oswestry Disability Index score was 42.5, post-revision score was 34.5 (P = 0.0203). The overall prevalence of pseudarthrosis was 10.5% of which 61% occurred at the actual PSO site and Scoliosis Research Society and Oswestry Disability Index scores improved significantly after pseudarthrosis repair. 4.


Economic evaluation of OROS hydromorphone for chronic pain: a Pan-European perspective.
OROS hydromorphone (osmotic extended-release oral delivery system [OROS] hydromorphone) is a long-acting opioid analgesic, which is approved in Europe for the management of severe pain. The authors aimed to estimate the economic value of this product relative to other widely used oral opioids, including sustained-release morphine, extended-release (ER) oxycodone, and twice-daily (bid) hydromorphone. An adaptable, decision-analytic cost-utility model was developed. Separate versions of the model were developed for five European countries: Germany, Denmark, Slovakia, Portugal, and Italy. OROS hydromorphone represents a cost-effective alternative to other strong oral opioids in the treatment of both nonmalignant and malignant pain in all five countries. In the treatment of chronic severe nonmalignant pain, OROS hydromorphone was dominant (ie, lower cost and incremental quality-adjusted life years gains) when compared with ER oxycodone in Denmark and bid hydromorphone in Germany. Likewise, OROS hydromorphone was dominant in the treatment of chronic severe malignant pain when compared with ER oxycodone in both Germany and Denmark and when compared with bid hydromorphone in all markets where hydromorphone was marketed. This model demonstrates the cost effectiveness of OROS hydromorphone relative to other strong oral opioids in the treatment of chronic severe malignant and nonmalignant pain.


Association studies of sporadic Parkinson's disease in the genomic era.
Parkinson's disease is a common age-related progressive neurodegenerative disorder. Over the last 10 years, advances have been made in our understanding of the etiology of the disease with the greatest insights perhaps coming from genetic studies, including genome-wide association approaches. These large scale studies allow the identification of genomic regions harboring common variants associated to disease risk. Since the first genome-wide association study on sporadic Parkinson's disease performed in 2005, improvements in study design, including the advent of meta-analyses, have allowed the identification of ~21 susceptibility loci. The first loci to be nominated were previously associated to familial PD (SNCA, MAPT, LRRK2) and these have been extensively replicated. For other more recently identified loci (SREBF1, SCARB2, RIT2) independent replication is still warranted. Cumulative risk estimates of associated variants suggest that more loci are still to be discovered. Additional association studies combined with deep re-sequencing of known genome-wide association study loci are necessary to identify the functional variants that drive disease risk. As each of these associated genes and variants are identified they will give insight into the biological pathways involved the etiology of Parkinson's disease. This will ultimately lead to the identification of molecules that can be used as biomarkers for diagnosis and as targets for the development of better, personalized treatment.