Patient feature based dosimetric Pareto front prediction in esophageal cancer radiotherapy.
To investigate the feasibility of the dosimetric Pareto front (PF) prediction based on patient's anatomic and dosimetric parameters for esophageal cancer patients. Eighty esophagus patients in the authors' institution were enrolled in this study. A total of 2928 intensity-modulated radiotherapy plans were obtained and used to generate PF for each patient. On average, each patient had 36.6 plans. The anatomic and dosimetric features were extracted from these plans. The mean lung dose (MLD), mean heart dose (MHD), spinal cord max dose, and PTV homogeneity index were recorded for each plan. Principal component analysis was used to extract overlap volume histogram (OVH) features between PTV and other organs at risk. The full dataset was separated into two parts; a training dataset and a validation dataset. The prediction outcomes were the MHD and MLD. The spearman's rank correlation coefficient was used to evaluate the correlation between the anatomical features and dosimetric features. The stepwise multiple regression method was used to fit the PF. The cross validation method was used to evaluate the model. With 1000 repetitions, the mean prediction error of the MHD was 469 cGy. The most correlated factor was the first principal components of the OVH between heart and PTV and the overlap between heart and PTV in Z-axis. The mean prediction error of the MLD was 284 cGy. The most correlated factors were the first principal components of the OVH between heart and PTV and the overlap between lung and PTV in Z-axis. It is feasible to use patients' anatomic and dosimetric features to generate a predicted Pareto front. Additional samples and further studies are required improve the prediction model.


Mechanisms of coronary spasm of isolated human epicardial coronary segments excised 3 to 5 hours after sudden death.
Isolated segments of epicardial coronary artery with and without severe atherosclerotic lesions excised from human hearts 3 to 5 hours after sudden coronary death demonstrated spontaneous contractile activity that was dependent on the external calcium level and was inhibited by calcium antagonists and activation of beta-adrenoceptors (isoproterenol and high concentrations of norepinephrine). Isoproterenol, with a median effective dose (ED50) of 6.3 X 10(-7) M, relaxed coronary segments that had been precontracted with 30 mM potassium. Stimulation of the alpha-adrenoceptors activated spontaneous contractions and increased tension. Norepinephrine ED50 (in the presence of 10(-6) M propranolol) was 2.3 X 10(-7) M, and tension at a maximal concentration of 10(-4) M was 385.4 +/- 51.4 mg. The ED50 for acetylcholine and histamine, the potent activators of coronary segment tone and phasic contractility, was 3.98 X 10(-7) and 8.9 X 10(-7) M, respectively; the maximal increase in tension was 1,079.5 +/- 175 (at 10(-4) M) and 1,131.3 +/- 302 mg (at 10(-5) M), respectively. Acetylcholine and histamine increased whereas high concentrations of norepinephrine failed to inhibit rhythmic activity and tension of coronary artery segments with severe atherosclerotic lesions. Membrane electrogenic mechanisms and ways of activating the contractile elements of human coronary artery smooth muscle are discussed.


Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.
The molecular basis of Kufs disease is unknown, whereas a series of genes accounting for most of the childhood-onset forms of neuronal ceroid lipofuscinosis (NCL) have been identified. Diagnosis of Kufs disease is difficult because the characteristic lipopigment is largely confined to neurons and can require a brain biopsy or autopsy for final diagnosis. We mapped four families with Kufs disease for whom there was good evidence of autosomal-recessive inheritance and found two peaks on chromosome 15. Three of the families were affected by Kufs type A disease and presented with progressive myoclonus epilepsy, and one was affected by type B (presenting with dementia and motor system dysfunction). Sequencing of a candidate gene in one peak shared by all four families identified no mutations, but sequencing of CLN6, found in the second peak and shared by only the three families affected by Kufs type A disease, revealed pathogenic mutations in all three families. We subsequently sequenced CLN6 in eight other families, three of which were affected by recessive Kufs type A disease. Mutations in both CLN6 alleles were found in the three type A cases and in one family affected by unclassified Kufs disease. Mutations in CLN6 are the major cause of recessive Kufs type A disease. The phenotypic differences between variant late-infantile NCL, previously found to be caused by CLN6, and Kufs type A disease are striking; there is a much later age at onset and lack of visual involvement in the latter. Sequencing of CLN6 will provide a simple diagnostic strategy in this disorder, in which definitive identification usually requires invasive biopsy.


One-dimensional nearly free electron states in borophene.
Two-dimensional boron (borophene) features structural polymorphs and distinct in-plane anisotropy, opening opportunities to achieve tailored electronic properties by intermixing different phases. Here, using scanning tunneling spectroscopy combined with first-principles calculations, delocalized one-dimensional nearly free electron states (NFE) in the (2,3) or β12 borophene sheet on the Ag(111) surface were observed. The NFE states emerge from a line defect in borophene, manifested as a structural unit of the (2,2) or χ3 sheet, which creates an in-plane potential well that shifts the states toward the Fermi level. The NFE states are held near the 2D plane of borophene, rather than in the vacuum region as observed in other nanostructures. Furthermore, borophene can provide a rare prototype to further study novel NFE behaviors, which may have potential applications in transport or field emission nanodevices based on boron.


Inhibition of rabbit muscle aldolase by phosphorylated aromatic compounds.
The interactions of the phosphorylated derivatives of hydroquinone (HQN-P2), resorcinol (RSN-P2), 4-hydroxybenzaldehyde (HBA-P) and 2, 4-dihydroxybenzaldehyde (DHBA-P; phosphate group at position 4) with fructose bisphosphate aldolase were analysed by enzyme kinetics, UV/visible difference spectroscopy and site-directed mutagenesis. Enzyme activity was competitively inhibited in the presence of HQN-P2, RSN-P2 and HBA-P, whereas DHBA-P exhibited slow-binding inhibition. Inhibition by DHBA-P involved active-site Schiff-base formation and required a phenol group ortho to the aldehyde moiety. Rates of enzyme inactivation and of Schiff-base formation by DHBA-P were identical, and corresponded to 3.2-3.5 DHBA-P molecules covalently bound per aldolase tetramer at maximal inactivation. Site-directed mutagenesis of the active-site lysine residues at positions 107, 146 and 229 was found to be consistent with Schiff-base formation between DHBA-P and Lys-146, and this was promoted by Lys-229. Mutation of Glu-187, located vicinally between Lys-146 and Lys-229 in the active site, perturbed the rate of Schiff-base formation, suggesting a functional role for Glu-187 in Schiff-base formation and stabilization. The decreased cleavage activity of the active-site mutants towards fructose 1, 6-bisphosphate is consistent with a proton-transfer mechanism involving Lys-229, Glu-187 and Lys-146.


Ophthalmic artery catheterization for retinoblastoma treatment: does reflux affect tumor response?
Intra-arterial chemotherapy (IAC) for retinoblastoma (Rb) has been established as a primary treatment for the disease. To determine whether the presence of reflux into the ICA is associated with tumor response or with any other adverse events in pediatric retinoblastoma patients. A retrospective chart review was performed for patients diagnosed with Rb and managed with ophthalmic artery catheterization (OAC). The total study cohort included 205 Rb tumors of 205 eyes in 194 consecutive patients who underwent 624 successful intra-arterial chemotherapy infusions using OAC. Of the 205 eyes, 65 eyes (32.7%) underwent 157 OAC procedures constituted group A (no reflux), 64 eyes (31.2%) underwent 236 OAC procedures constituted group B (variable pattern), and 74 eyes (36.1%) underwent 231 OAC procedures constituted group C (reflux). There was no significant difference in baseline characteristics between the three cohorts. Also, there was no significant difference in tumor characteristics between the three groups, except for genetic status. There was no significant difference between the three groups in terms of tumor response at completion of the treatment regimen. Complete tumor response was achieved at 70.2% in Group A, at 83.3% in Group B, and at 78.5% in group C (P=0.39). Similarly, eye enucleation occurred at 38.5% in group A, 31.8% in group B, and 31.5% in group C. None of the patients in both groups had any neurological adverse events or new onset of seizures. The presence of reflux, which may complicate the procedure and prolong it, was not associated with poor outcomes in our analysis.


Distinct effects of Vibrio cholerae haemagglutinin/protease on the structure and localization of the tight junction-associated proteins occludin and ZO-1.
Vibrio cholerae produces a little-studied cytotoxin, haemagglutinin/protease (HA/P), in addition to several better-characterized enterotoxins, i.e. cholera toxin (CT), zonula occludens toxin (ZOT) and accessory cholera enterotoxin (Ace). We have found recently that HA/P perturbs the barrier function of Mardin-Darby canine kidney epithelial cell line I (MDCK-I) by affecting the intercellular tight junctions (TJs) and the F-actin cytoskeleton. In the present study we have assessed more specifically how TJs are affected by HA/P by investigating the cellular localization and biochemical integrity of two well-characterized TJ-associated proteins, occludin and ZO-1. Western blot analysis showed that occludin bands of 66-85 kDa were digested by HA/P to two predominant bands of around 50 kDa and 35 kDa, and that this degradation was greatly attenuated when the specific bacterial metalloproteinase inhibitor Zincov was co-administered. Trypsin, on the other hand, did not degrade occludin when it was applied in the same way, suggesting that the degradation of occludin by HA/P is an early and specific event. The other TJ-associated protein ZO-1 was not degraded by HA/P in parallel experiments, suggesting the selectivity of HA/P-associated protein degradation. Moreover, immunofluorescence labelling and confocal microscopy showed that ZO-1, but not occludin, around cell-cell boundaries was rearranged by HA/P treatment. Since ZO-1 is located on the inside of the plasma membrane and is directly associated with occludin, the results indicate that breakdown of occludin may send signals to ZO-1 that affect its organization and the structure of the F-actin cytoskeleton. Our finding that the zinc-containing metalloprotease of V. cholerae specifically degraded occludin suggests that specific degradation of important host proteins by bacterial zinc-containing metalloproteases may be an important mechanism in microbial pathogenesis.


Ultrastructural localization of spicule matrix proteins in normal and metalloproteinase inhibitor-treated sea urchin primary mesenchyme cells.
Studies of the sea urchin larval skeleton have contributed greatly to our understanding of the process of biomineralization. In this study we have undertaken an investigation of the morphology of skeleton formation and the localization of proteins involved in the process of spicule formation at the electron microscope level. Sea urchin primary mesenchyme cells undergo a number of morphological changes as they synthesize the larval skeleton. They form a large spicule compartment that surrounds the growing spicule and, as spicule formation comes to an end, the density of the cytoplasm decreases. Inhibition of spicule formation by specific matrix metalloproteinase inhibitors or serum deprivation has some subtle effects on the morphology of cells and causes the accumulation of specific classes of vesicles. We have localized proteins of the organic matrix of the spicule and found that one protein, SM30, is localized to the Golgi apparatus and transport vesicles in the cytoplasm as well as throughout the occluded protein matrix of the spicule itself. This localization suggests that SM30 is an important structural protein in the spicule. Another spicule matrix protein, SM50, has a similar cytoplasmic localization, but in the spicule much of it is localized at the periphery of the spicule compartment, and consequently it may play a role in the assembly of new material onto the growing spicule or in the maintenance of the integrity of the matrix surrounding the spicule.


An approach in mathematical modeling of an upflow packed-bed reactor for enzymatic hydrolysis of wheat straw.
The behavior of a packed-bed reactor for enzymatic hydrolysis of pretreated wheat straw has been described by means of a mathematical model. The flow pattern has been evaluated by residence time distribution experiments. Small deviations from ideal plug flow behavior were found using the dispersion model. The kinetic model proposed for enzymatic hydrolysis of cellulosic fraction of pretreated wheat straw has been derived from batch experimental data. Variations of enzyme concentration throughout the straw bed have been approximately described using a ramp variation of adsorbed enzyme. The final explains qualitatively the experimental results.


Polymorphism -433 C>T of the Osteopontin gene is associated with the susceptibility to develop gliomas and their prognosis in a Chinese cohort.
To investigate role of the Osteopontin (OPN) genetic polymorphisms in the susceptibility to gliomas and their prognosis. A total of 248 Chinese glioma patients and 281 age and sex matched healthy controls were recruited. The genetic polymorphisms at three loci, namely, -156 GG>G, -443 C>T and -66T>G, were determined. The log-rank test and Kaplan- Meier analysis were introduced to assess the effect of OPN gene polymorphisms on patient survival. We found that the genotype frequencies of OPN -443 C>T polymorphism were significantly different between glioma patients and controls. Multivariable analyses showed a higher risk for gliomas in -443 CC genotype carriers compared to -443TT carriers (P<0.001). In addition, we also found the OPN -443 C>T polymorphism was closely related to the gliomas' tumor grade. The -443 C>T polymorphism also affected the tumor OPN expression level, but not the serum OPN level. More importantly, the -443 C>T polymorphism was significantly associated with the prognosis of these patients regardless of their treatment status. The patients with -443CC genotype had a poorer prognosis than those with -443TT and -443CT genotypes. In contrast, the -156 G>GG and -66T>G polymorphisms were not associated with risk, clinical characteristics, or prognosis of gliomas. This study suggests that the -443C>T gene polymorphisms may be used as a molecular marker for glioma occurrence and clinical outcome in glioma patients.


Density functional study for the bridged dinuclear center based on a high-resolution X-ray crystal structure of ba3 cytochrome c oxidase from Thermus thermophilus.
Strong electron density for a peroxide type dioxygen species bridging the Fea3 and CuB dinuclear center (DNC) was observed in the high-resolution (1.8 Å) X-ray crystal structures (PDB entries 3S8G and 3S8F) of ba3 cytochrome c oxidase (CcO) from Thermus thermophilus. The crystals represent the as-isolated X-ray photoreduced CcO structures. The bridging peroxide was proposed to arise from the recombination of two radiation-produced HO(•) radicals formed either very near to or even in the space between the two metals of the DNC. It is unclear whether this peroxide species is in the O2(2-), O2(•)(-), HO2(-), or the H2O2 form and what is the detailed electronic structure and binding geometry including the DNC. In order to answer what form of this dioxygen species was observed in the DNC of the 1.8 Å X-ray CcO crystal structure (3S8G), we have applied broken-symmetry density functional theory (BS-DFT) geometric and energetic calculations (using OLYP potential) on large DNC cluster models with different Fea3-CuB oxidation and spin states and with O2(2-), O2(•)(-), HO2(-), or H2O2 in the bridging position. By comparing the DFT optimized geometries with the X-ray crystal structure (3S8G), we propose that the bridging peroxide is HO2(-). The X-ray crystal structure is likely to represent the superposition of the Fea3(2+)-(HO2(-))-CuB(+) DNC's in different states (Fe(2+) in low spin (LS), intermediate spin (IS), or high spin (HS)) with the majority species having the proton of the HO2(-) residing on the oxygen atom (O1) which is closer to the Fea3(2+) site in the Fea3(2+)-(HO-O)(-)-CuB(+) conformation. Our calculations show that the side chain of Tyr237 is likely trapped in the deprotonated Tyr237(-) anion form in the 3S8G X-ray crystal structure.


Thyroid Hormone Distributor Proteins During Development in Vertebrates.
Thyroid hormones (THs) are ancient hormones that not only influence the growth, development and metabolism of vertebrates but also affect the metabolism of (at least some) bacteria. Synthesized in the thyroid gland (or follicular cells in fish not having a discrete thyroid gland), THs can act on target cells by genomic or non-genomic mechanisms. Either way, THs need to get from their site of synthesis to their target cells throughout the body. Despite being amphipathic in structure, THs are lipophilic and hence do not freely diffuse in the aqueous environments of blood or cerebrospinal fluid (in contrast to hydrophilic hormones). TH Distributor Proteins (THDPs) have evolved to enable the efficient distribution of THs in the blood and cerebrospinal fluid. In humans, the THDPs are albumin, transthyretin (TTR), and thyroxine-binding globulin (TBG). These three proteins have distinct patterns of regulation in both ontogeny and phylogeny. During development, an additional THDP with higher affinity than those in the adult, is present during the stage of peak TH concentrations in blood. Although TTR is the only THDP synthesized in the central nervous system (CNS), all THDPs from blood are present in the CSF (for each species). However, the ratio of albumin to TTR differs in the CSF compared to the blood. Humans lacking albumin or TBG have been reported and can be asymptomatic, however a human lacking TTR has not been documented. Conversely, there are many diseases either caused by TTR or that have altered levels of TTR in the blood or CSF associated with them. The first world-wide RNAi therapy has just been approved for TTR amyloidosis.


Solvent independent symmetry-breaking charge separation in terrylenediimide guanine-quadruplex nanoparticles.
G-quadruplex assemblies are a promising tool for self-assembling π-stacked chromophore arrays to better understand their photophysics. We have shown that coupling a single guanine moiety to terrylenediimide (TDI) produces a structure (GTDI) that self-assembles in tetrahydrofuran (THF) into a nearly monodisperse guanine-quadruplex structure having 16 π-stacked layers (GTDI4)16. The TDI surfaces were determined to have a high degree of cofacial overlap and underwent quantitative symmetry-breaking charge separation (SB-CS) upon photoexcitation. Here, we more deeply examine the relationship between solvent and aggregate formation and develop insights into structure-function relationships over a variety of solvent polarities and hydrogen-bonding capabilities. At high concentrations, GTDI assembles into guanine-quadruplex structures (GTDI4)16 in THF and toluene, as well as (GTDI4)9 in pyridine and benzonitrile. Transient absorption spectroscopy shows that SB-CS occurs in all solvents, regardless of their static dielectric constants, but the SB-CS yield is determined by structure. Solvent polarity independent SB-CS generation is also observed in GTDI films, where there is a complete absence of solvent.


Cytokine activity in cancer-related anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate.
The characteristic clinical picture of anorexia, tissue wasting, loss of body weight accompanied by a decrease in muscle mass and adipose tissue, and poor performance status that often precedes death has been named the cancer-related anorexia/cachexia syndrome (CACS). Chronic administration of pro-inflammatory cytokines, including interleukin-I (IL-I), IL-6, and tumor necrosis factor (TNF), either alone or in combination, is capable of reproducing the different features of CACS. High serum levels of these cytokines have been found in cancer patients, which seem to correlate with progression of the tumor. This article describes a series of experimental and clinical studies demonstrating that: (1) high serum levels of some cytokines, including IL-I, IL-6, and TNF, are present in advanced-stage cancer patients, particularly those with CACS; (2) megestrol acetate (MA) has a beneficial therapeutic effect on CACS symptoms, such as appetite, body weight, and quality of life; (3) MA downregulates the synthesis and release of cytokines and relieves the symptoms of CACS; (4) cytokines play a key role in the onset of CACS; (5) medroxyprogesterone acetate (MPA) reduces the in vitro production of cytokines and serotonin (5-hydroxytryptamine, 5-HT) by peripheral blood mononuclear cells (PBMC) of cancer patients; and (6) MA and MPA reduce the cisplatin-induced 5-HT release in vitro from PBMC of cancer patients. Based on these results, a clinical study incorporating MA/MPA in combination with chemotherapy or chemoimmunotherapy may be warranted. In addition, it has been recently shown that "oxidative stress" resulting from reactive oxygen species, which can be induced by pro-inflammatory cytokines, is involved in tissue wasting and CACS. These results suggest promising approaches for the prevention and treatment of cytokine-induced CACS based on MA, MPA, and metabolic antioxidants.


Relationships between body mass index, mental health, and suicidal ideation: population perspective using two methods.
The aim of the present study was to examine the relationship between body mass index (BMI), mental health, and suicidal ideation in a general population. Two random and representative samples were drawn from the South Australian population. The interview techniques differed, as did the measures of depression and suicidality. One involved 3034 people in face-to-face interviews, and the other involved 30 214 persons providing information via a computer-assisted telephone interviewing (CATI) system. BMI was classified according to World Health Organization criteria. In face-to-face interviews, major depression was defined by the Primary Care Evaluation of Mental Disorders (PRIME-MD) and suicidal ideation by direct enquiry. In the CATI data, psychological distress was assessed on the Kessler 10 instrument and suicidal ideation by four items on the General Health Questionnaire (GHQ). Data analysis controlled for demographic and physical health variables. In the face-to-face interviews, the combined obese and morbidly obese men were significantly less likely to have major depression or suicidal ideation than those of a healthy weight. For the telephone interview-derived data, the only significant finding was for overweight women to report less psychological distress than those of a healthy weight. It is no longer tenable to assume that increased BMI is necessarily associated with major depression, psychological distress, or suicidal ideation. Indeed, it appears protective for some people.


Altered kynurenine pathway metabolites in a mouse model of human attention-deficit hyperactivity/autism spectrum disorders: A potential new biological diagnostic marker.
Deleterious mutations in patchd1 domain containing 1 (PTCHD1) gene have been identified in patients with intellectual disability and/or autism spectrum disorder (ASD). To clarify the causal relationship between Ptchd1 deficiency and behavioral defects relevant to neurodevelopmental disorders, we generated global Ptchd1 knockout (KO) mice. Ptchd1 KO mice displayed hyperlocomotion, increased impulsivity, and lower recognition memory, which resemble attention-deficit hyperactivity disorder (ADHD)-like behaviors. Acute or chronic treatment with atomoxetine ameliorated almost all behavioral deficits in Pthcd1 KO mice. We next determined possible involvement of the kynurenine pathway (KP) metabolites in neurodevelopmental disorders in Ptchd1 KO mice and assessed the potential of KP metabolites as biomarkers for ADHD and/or ASD. Ptchd1 KO mice showed drastic changes in KP metabolite concentrations in the serum and the brain, indicating that the activated KP is associated with ADHD-like behaviors. Our findings indicate that Ptchd1 KO mice can be used as an animal model of human ADHD and/or ASD, and KP metabolites are potential diagnostic biomarkers for neurodevelopmental disorders.


The surveillance of infectious diseases.
Surveillance is the collection, collation, and analysis of data and the dissemination to those who need to know so that an action can result. This article describes the clinician's critical role in disease reporting and outlines the benefits of surveillance to clinical practice. Four commonly used systems of disease surveillance are notifiable disease reporting, laboratory-based surveillance, hospital-based surveillance, and population-based surveillance. We analyze the relative strengths and limitations of each of these systems and present current efforts to evaluate and improve surveillance activities.


Empathy at work: The role of age and emotional job demands.
Empathy-which typically instigates prosocial behavior-comprises both cognitive and affective facets. Research suggests that the cognitive facet of empathy (empathic accuracy) declines with age, whereas the affective facets of empathy (emotional congruence and sympathy) remain stable or increase with age. Going beyond main effects of age, we tested whether working in occupations with varying emotional job demands (EJDs) moderates the effects of age on empathy. We predicted that emotionally demanding occupations provide opportunities to practice empathy and, as a result, may lessen the negative relationship between age and empathic accuracy and/or strengthen the (positive) relationship between age and the affective facets of empathy. A sample of 128 employees (19-65 years) who differed in self-reported EJDs was recruited. Participants viewed film clips portraying different persons retelling a work event during which they experienced positive or negative emotions. After each clip, participants rated the intensity of the protagonist's and their own emotions. Consistent with prior research, our analyses revealed a negative association between age and empathic accuracy, while there were no age differences in emotional congruence and a positive association between age and sympathy. Only the relationship between age and emotional congruence was moderated by EJDs. Contrary to our prediction, relatively older employees in emotionally demanding jobs experienced lower emotional congruence than younger employees. This may suggest that people learn about the double-edged nature of sharing other's feelings as they progress in their career, and thus, keep a healthy distance. Implications for age-comparative research on prosocial processes across adulthood are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Ankle mechanics during sidestep cutting implicates need for 2-degrees of freedom powered ankle-foot prostheses.
The ankle joint of currently available powered prostheses is capable of controlling one degree of freedom (DOF), focusing on improved mobility in the sagittal plane. To increase agility, the requirements of turning in prosthesis design need to be considered. Ankle kinematics and kinetics were studied during sidestep cutting and straight walking. There were no significant differences between the ankle sagittal plane mechanics when comparing sidestep cutting and straight walking; however, significant differences were observed in ankle frontal plane mechanics. During straight walking, the inversion-eversion (IE) angles were smaller than with sidestep cutting. The ankle that initiated the sidestep cutting showed progressively increasing inversion from 2 to 13 degrees while the following contralateral step showed progressively decreasing inversion from 8 to -4 degrees during normal walking speed. The changes in IE kinematics were the most significant during sidestep cutting compared with straight walking. The IE moments of the step that initiated the sidestep cutting were always in eversion, acting as a braking moment opposing the inverting motion. This suggests that an ankle-foot prosthesis with active DOFs in the sagittal and frontal planes will increase the agility of gait for patients with limb loss.


The effects of prolonged abstinence on the processing of smoking cues: an ERP study among smokers, ex-smokers and never-smokers.
Processing bias is an important feature of substance abuse. The issue whether processing bias is a more or less permanent feature of nicotine addiction remains to be resolved. The present study addresses the role of smoking status on smoking-related processing bias. We employed Event-Related Brain Potentials (ERPs) as measure of processing bias to investigate this issue. Further, self-report measures of nicotine craving and pleasantness ratings of smoking stimuli were obtained. Three groups, smokers, ex-smokers and never-smokers, were compared on their electrophysiological brain response to smoking-related and neutral pictures. The present study shows that both the P300 and SPW amplitudes in response to smoking-related pictures are significantly more enhanced for smokers than for ex-smokers and never-smokers at frontal and central sites, whereas the magnitude of the P300 and SPW amplitudes in response to neutral pictures does not differ between the three groups. Accordingly, it can be concluded that smokers show more bias for smoking-related pictures than ex-smokers and smokers. Because there is no significant difference between the P300 and SPW amplitudes of ex-smokers and never-smokers, it can also be concluded that ex-smokers display the same (low) level of processing bias as never-smokers. In addition, nicotine-craving ratings and pleasantness ratings of smoking stimuli were higher in smokers compared to ex-smokers. It can be concluded that the smoking-related craving, pleasantness rating, and processing bias decreases after a period of prolonged abstinence.


Innervation of the Anterior Capsule of the Human Knee: Implications for Radiofrequency Ablation.
Chronic knee pain is common in all age groups. Some patients who fail conservative therapy benefit from radiofrequency neurotomy. Knowledge of the anatomy is critical to ensure a successful outcome. The purpose of this study was to reanalyze the innervation to the anterior knee capsule from the perspective of the interventional pain practitioner. The study included a comprehensive literature review followed by dissection of 8 human knees to identify the primary capsular innervation of the anterior knee joint. Photographs and measurements were obtained for each relevant nerve branch. Stainless-steel wires were placed along the course of each primary innervation, and radiographs were obtained. Literature review revealed a lack of consensus on the number and origin of nerve branches innervating the anterior knee capsule. All dissections revealed the following 6 nerves: superolateral branch from the vastus lateralis, superomedial branch from the vastus medialis, middle branch from the vastus intermedius, inferolateral (recurrent) branch from the common peroneal nerve, inferomedial branch from the saphenous nerve, and a lateral articular nerve branch from the common peroneal nerve. Nerve branches showed variable proximal trajectories but constant distal points of contact with femur and tibia. The inferolateral peroneal nerve branch was found to be too close to the common peroneal nerve, making it inappropriate for radiofrequency neurotomy. The innervation of the anterior capsule of the knee joint seems to follow a constant pattern making at least 3 of these nerves accessible to percutaneous ablation. To optimize clinical outcome, well-aligned radiographs are critical to guide lesion placement.


Choriocarcinoma after hydatidiform mole. Studies related to effectiveness of follow-up practice after hydatidiform mole.
Chemotherapy, in conjunction with other methods of treatment, was used in 100 patients with invasive hydatidiform mole or choriocarcinoma following mole. When treatment was instituted within two to six months of the antecedent mole serious drug resistance was not encountered, drug toxicity was slight, the duration of treatment was comparatively short, and sustained remissions were obtained in 57 out of 60 patients. When the start of chemotherapy was delayed beyond six months drug resistance occurred in many instances, toxicity was often severe, the duration of treatment was much longer, and sustained remissions were obtained in 22 out of 40 patients.The practice of giving prophylactic chemotherapy to all patients with mole is not established as effective or safe. Differences in the social background to hydatidiform mole in different geographical areas may be such that conclusions based on evidence from one area are not necessarily applicable to another.Careful follow-up after mole remains essential, though present methods often fail to ensure recognition of choriocarcinoma while it is still curable. Standard qualitative and quantitative methods for detecting the continued excretion of chorionic gonadotrophin, though useful, are sometimes too insensitive. It is suggested that to supplement local arrangements some form of centralized or regionalized follow-up service based on notification of patients with hydatidiform mole, and making use of radioimmunoassays for chorionic gonadotrophin, could reduce deaths attributable to late diagnosis.


Estrogen and estrogen receptors chauffeur the sex-biased autophagic action in liver.
Autophagy, or cellular self-digestion, is an essential cellular process imperative for energy homeostasis, development, differentiation, and survival. However, the intrinsic factors that bring about the sex-biased differences in liver autophagy are still unknown. In this work, we found that autophagic genes variably expresses in the steroidogenic tissues, mostly abundant in liver, and is influenced by the individual's sexuality. Starvation-induced autophagy in a time-dependent female-dominated manner, and upon starvation, a strong gender responsive circulating steroid-HK2 relation was observed, which highlighted the importance of estrogen in autophagy regulation. This was further confirmed by the enhanced or suppressed autophagy upon estrogen addition (male) or blockage (female), respectively. In addition, we found that estrogen proved to be the common denominator between stress management, glucose metabolism, and autophagic action in female fish. To understand further, we used estrogen receptor (ER)α- and ER-β2-knockout (KO) medaka and found ER-specific differences in sex-biased autophagy. Interestingly, starvation resulted in significantly elevated mTOR transcription (compared with control) in male ERα-KO fish while HK2 and ULK activation was greatly decreased in both KO fish in a female oriented fashion. Later, ChIP analysis confirmed that, NRF2, an upstream regulator of mTOR, only binds to ERα, while both ERα and ERβ2 are effectively pulled down the HK2 and LC3. FIHC data show that, in both ER-KO fish, LC3 nuclear-cytoplasmic transport and its associated pathways involving SIRT1 and DOR were greatly affected. Cumulatively, our data suggest that, ERα-KO strongly affected the early autophagic initiation and altered the LC3 nuclear-cytoplasmic translocation, thereby influencing the sex-biased final autophagosome formation in medaka. Thus, existence of steroid responsive autophagy regulatory-switches and sex-biased steroid/steroid receptor availability influences the gender-skewed autophagy. Expectedly, this study may furnish newer appreciation for gender-specific medicine research and therapeutics.


[Semantic processing of words in selective listening: an examination using recognition tests and event-related brain potentials].
Two experiments were conducted to investigate the degree of semantic processing for unattended words. In a dichotic listening task, each participant was required to attend selectively to either a word sequence in one ear or a speech passage in the opposite ear. The selective listening was confirmed by attenuated P1-N1 and N400 waves of the event-related brain potential to unattended words. The N400 attenuation with semantic priming was observed only for attended words. In a following recognition test with a booklet and auditory presentation, the percentage of false alarms for "new" words (or lures) semantically related to "old" words was higher when the "old" words were attended in selective listening than when unattended. These findings suggest that selective attention can act before and/or at a level of semantic processing.


[Substantiation of preclinical manifestations of bronchopulmonary diseases in workers exposed to organic dust].
144 workers of two Ukrainian fodder plants have been examined. Respiratory troubles presenting as cough, expectoration, shortness of breath have come to be the case from not only exposure to high concentrations of endotoxins but from low-level exposures as well. The prevalence of the toxic organic dust syndrome, musocal irritation syndrome, bronchial hyper-reactivity and obstructive changes in the ventilation function of the lungs have been found out to be associated with endotoxin levels in the air of the work environment of the production floor-area. Regarded as valid screenring procedures to early identify those persons predisposed to obstructive changes in the function of external respiration are pharmacological loading tests. Sanitary-and-hygienic and treatment-and-prophylactic measures are proposed to prevent development of occupational diseases in workers exposed to organic dust.


Characterizing the Semiconductor Nanocrystal Surface through Chemical Reactivity.
ConspectusMany desirable and undesirable properties of semiconductor nanocrystals (NCs) can be traced to the NC surface due to the large surface-to-volume ratio. Therefore, precise control of the NC surface is imperative to achieve NCs with the desired qualities. Ligand-specific reactivity and surface heterogeneity make it difficult to accurately control and tune the NC surface. Without a molecular-level appreciation of the NC surface chemistry, modulating the NC surface is impossible and the risk of introducing deleterious surface defects is imminent. To gain a more comprehensive understanding of the surface reactivity, we have utilized a variety of spectroscopic techniques and analytical methods in concert.This Account describes our use of robust characterization techniques and ligand exchange reactions in effort to establish a molecular-level understanding of NC surface reactivity. The utility of NCs in target applications such as catalysis and charge transfer hangs on precise tunability of NC ligands. Modulating the NC surface requires the necessary tools to monitor chemical reactions. One commonly utilized analytical method to achieve targeted surface compositions is 1H nuclear magnetic resonance (NMR) spectroscopy. Here we describe our use of 1H NMR spectroscopy to monitor chemical reactions at CdSe and PbS NC surfaces to identify ligand specific reactivity. However, seemingly straightforward ligand exchange reactions can vary widely depending on the NC materials and anchoring group. Some non-native X-type ligands will irreversibly displace native ligands. Other ligands exist in equilibrium with native ligands. Depending on the application, it is important to understand the nature of exchange reactions. This level of understanding can be obtained by extracting exchange ratios, exchange equilibrium, and reaction mechanism information from 1H NMR spectroscopy to establish precise NC reactivity.Reactivity that occurs through multiple, parallel ligand exchange mechanisms can involve both the liberation of metal-based Z-type ligands in addition to reactivity of X-type ligands. In these reactions, 1H NMR spectroscopy fails to discern between an X-type oleate or a Z-type Pb(oleate)2 because only the alkene resonance of the organic constituent is probed by this method. Multiple, parallel reaction pathways occur when thiol ligands are introduced to oleate-capped PbS NCs. This necessitated the use of synergistic characterization methods including 1H NMR spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and inductively coupled plasma mass spectrometry (ICP-MS) to characterize both surface-bound and liberated ligands.Similar analytical methods have been employed to probe the NC topology, which is an important, but often overlooked, component to NC reactivity given the facet-specific reactivity of PbS NCs. Through the tandem use of NMR spectroscopy and ICP-MS, we have monitored the liberation of Pb(oleate)2 as an L-type ligand is titrated to the NC to determine the quantity and equilibrium of Z-type ligands. By studying a variety of NC sizes, we correlated the number of liberated ligands with the size-dependent topology of PbS NCs.Lastly, we incorporate redox-active chemical probes into our toolbox to study NC surface defects. We describe how the site-specific reactivity and relative energetics of redox-active surface-based defects are elucidated using redox probes and show that this reactivity is highly dependent on the surface composition. This Account is designed to encourage readers to consider the necessary characterization techniques needed establish a molecular-level understanding of NC surfaces in their own work.


[Comparative techniques for the diagnosis of rabies and its incidence in Tamaulipas in 1987].
Rabies in suspect cases was diagnosed by immunofluorescence, histopathology and biological tests in samples from government health centers in Tamaulipas, Mexico during 1987. Comparative analysis between the diagnostic results and the epidemiological survey was performed. Brain samples of 278 suspect animals were studied; 45 cases were positive to rabies (16.1%). The centers providing high number of samples and positive cases correlate with counties of high human and canine population density, however, the percentage of positive cases versus samples sent does not correlate with the same counties, therefore making it possible to establish high risk areas. During spring, an increase of positive samples were received possibly associated with the canine breeding season. Urban rabies is a real problem in Tamaulipas, expressed by 97.7% of positive canine samples, 63.6% males and 36.3% females of an average age of fifteen months and were primarily of native breeds. Only 22% of positive cases had been previously vaccinated against rabies. A 56.3% incidence reduction versus the last four years was observed. It was concluded that a reduction of false positive results is possible when using the 3 diagnostic procedures described.


Paternal occupation and Wilms' tumour in offspring.
A case-control study was conducted to test the hypothesis that paternal occupation is a risk factor for Wilms' tumour in offspring. Occupations associated with exposure to lead (Pb) and to hydrocarbons were examined by computing odds ratios, all of which were greater than unity but not by a statistically significant margin. When painters were considered separately, children whose fathers had been so employed were six times more likely to develop Wilms' tumour than children whose fathers had other occupations. Like the results for the Pb and hydrocarbon related occupations, the estimated relative risk associated with painters did not reach statistical significance. Although these data require cautious interpretation because of the relatively small number of subjects, the results reported here are not wholly consistent with the results of the one previous study of paternal occupation and Wilms' tumour in offspring.


Long-term effects of cholinergic agonists on memory.
Animal models provide important information about strategies that can be used to assess the effects of chronic exposure to drugs or other compounds. Furthermore, when used in conjunction with analyses designed to utilize the many advantages of animal models to examine learning and memory, these kinds of experiments can have significant ramifications for assessing the mnemonic effects of chronic drug use in people. Finally, given that aging is accompanied by significant deterioration of neurochemical systems, which may compromise the functions of those systems, the results from the experiments with DFP predict that changes in learning and memory abilities that are not apparent in young individuals may begin to surface as those individuals age or may appear following any other kind of insult to their nervous system.


Bridging Adhesion of a Protein onto an Inorganic Surface Using Self-Assembled Dual-Functionalized Spheres.
For the bridging adhesion of different classes of materials in their intact functional states, the adhesion of biomolecules onto inorganic surfaces is a necessity. A new molecular design strategy for bridging adhesion was demonstrated by the introduction of two independent recognition groups on the periphery of spherical complexes self-assembled from metal ions (M) and bidentate ligands (L). These dual-functionalized M12L24 spheres were quantitatively synthesized in one step from two ligands, bearing either a biotin for streptavidin recognition or a titania-binding aptamer, and Pd(II) ions. The selective recognition of titania surfaces was achieved by ligands with hexapeptide aptamers (Arg-Lys-Leu-Pro-Asp-Ala: minTBP-1), whose fixation ability was enhanced by the accumulation effect on the surface of the M12L24 spheres. These well-defined spherical structures can be specifically tailored to promote interactions with both titania and streptavidin simultaneously without detrimentally affecting either recognition motif. The irreversible immobilization of the spheres onto titania was revealed quantitatively by quartz crystal microbalance measurements, and the adhesion of streptavidin to the titania surface mediated by the biotin surrounding the spheres was visually demonstrated by lithographic patterning experiments.


Cranial Suture Closure in Domestic Dog Breeds and Its Relationships to Skull Morphology.
Bulldog-type brachycephalic domestic dog breeds are characterized by a relatively short and broad skull with a dorsally rotated rostrum (airorhynchy). Not much is known about the association between a bulldog-type skull conformation and peculiar patterns of suture and synchondrosis closure in domestic dogs. In this study, we aim to explore breed-specific patterns of cranial suture and synchondrosis closure in relation to the prebasial angle (proxy for airorhynchy and thus bulldog-type skull conformation) in domestic dogs. For this purpose, we coded closure of 18 sutures and synchondroses in 26 wolves, that is, the wild ancestor of all domestic dogs, and 134 domestic dogs comprising 11 breeds. Comparisons of the relative amount of closing and closed sutures and synchondroses (closure scores) in adult individuals showed that bulldog-type breeds have significantly higher closure scores than non-bulldog-type breeds and that domestic dogs have significantly higher closure scores than the wolf. We further found that the prebasial angle is significantly positively correlated with the amount of closure of the basispheno-presphenoid synchondrosis and sutures of the nose (premaxillo-nasal and maxillo-nasal) and the palate (premaxillo-maxillary and interpalatine). Our results show that there is a correlation between patterns of suture and synchondrosis closure and skull shape in domestic dogs, although the causal relationships remain elusive.


Hormonal mechanisms of cooperative behaviour.
Research on the diversity, evolution and stability of cooperative behaviour has generated a considerable body of work. As concepts simplify the real world, theoretical solutions are typically also simple. Real behaviour, in contrast, is often much more diverse. Such diversity, which is increasingly acknowledged to help in stabilizing cooperative outcomes, warrants detailed research about the proximate mechanisms underlying decision-making. Our aim here is to focus on the potential role of neuroendocrine mechanisms on the regulation of the expression of cooperative behaviour in vertebrates. We first provide a brief introduction into the neuroendocrine basis of social behaviour. We then evaluate how hormones may influence known cognitive modules that are involved in decision-making processes that may lead to cooperative behaviour. Based on this evaluation, we will discuss specific examples of how hormones may contribute to the variability of cooperative behaviour at three different levels: (i) within an individual; (ii) between individuals and (iii) between species. We hope that these ideas spur increased research on the behavioural endocrinology of cooperation.


Intracellular third loop domain of angiotensin II type-2 receptor. Role in mediating signal transduction and cellular function.
The present study tests the hypothesis that the unique intracellular third loop domain of angiotensin II type-2 (AT2) receptor is essential for the subsequent intracellular signaling and plays an important role in mediating receptor function. Synthetic intracellular third loop peptide of the AT2 receptor (AT2-3LP, 22 amino acids) and control peptide consisting of the same amino acid composition in random sequence were delivered into adult rat aortic vascular smooth muscle cells by cationic liposome-mediated transfection. Successful intracellular peptide delivery was confirmed by microscopic localization of the fluorescein-labeled AT2-3LP within the cells and also by co-immunoprecipitation of the 125I-labeled 3LP complexed with Gi protein using anti-Gialpha antibody. The AT2-3LP-transfected cells showed reduction of serum-stimulated DNA synthesis and cell proliferation as well as a decrease in mitogen-activated protein kinase activity, simulating the effects of AT2 receptor stimulation. The antagonistic effect of the AT2-3LP on mitogen-activated protein kinase activity and DNA synthesis were reversed by pertussis toxin and sodium orthovanadate. Thus, our data suggest that the intracellular third loop domain of the AT2 receptor is closely linked with the cellular signaling pathways of vascular smooth muscle cells in which Gi and protein-phosphotyrosine phosphatase are involved, resulting in the alteration of mitogen-activated protein kinase activity and in growth inhibition.


Dietary protein level affects iridescent coloration in Anna's hummingbirds, Calypte anna.
Many animal displays involve colorful ornamental traits that signal an individual's quality as a mate or rival. Brilliant iridescent ornaments are common, but little is currently known about their production cost and signaling value. One potential cost of colorful ornaments is the acquisition of limited dietary resources that may be involved, directly or indirectly, in their production. Protein, the primary component of bird feathers and of many nanostructural components of iridescent traits, is naturally restricted in hummingbird diets (comprised mostly of sugars), suggesting that iridescent coloration may be especially challenging to produce in these animals. In this study, we experimentally investigated the effect of dietary protein availability during molt on iridescent color expression in male Anna's hummingbirds (Calypte anna). We fed captive birds either a 6% (high) or a 3% (low) protein diet and stimulated molt by plucking half the gorget and crown ornaments on each bird as well as the non-ornamental iridescent green tail feathers. We found that birds receiving more protein grew significantly more colorful crown feathers (higher red chroma and redder hue) than those fed the low-protein diet. Diet did not affect gorget coloration, but regrowth of feathers in captivity affected both gorget and crown coloration. Additionally, birds on the high-protein diet grew yellower (higher hue) green tail feathers than birds on the low-protein diet. These results indicate that iridescent ornamental feathers are sensitive to diet quality and may serve as honest signals of nutrition to mates or rivals. Further, because both ornamental and non-ornamental iridescent coloration were affected by conditions during their growth, iridescent color in these birds appears to be generally condition dependent.


Life after diagnosis and treatment of cancer in adulthood: contributions from psychosocial oncology research.
The number of individuals living with a history of cancer is estimated at 13.7 million in the United States and is expected to rise with the aging of the population. With expanding attention to the psychosocial and physical consequences of surviving illness, psychological science and evidence-based practice are making important contributions to addressing the pressing needs of cancer survivors. Research is demonstrating that adults diagnosed with cancer evidence generally positive psychosocial adjustment over time; however, a subset is at risk for compromised psychological and physical health stemming from long-term or late effects of cancer and its treatment. In this article, we characterize survivorship after medical treatment completion during the periods of reentry, early survivorship, and long-term survivorship. We describe the major psychosocial and physical sequelae facing adults during those periods, highlight promising posttreatment psychosocial and behavioral interventions, and offer recommendations for future research and evidence-based practice.


Separation of Macrophages and Fibroblasts Using Contactless Dielectrophoresis and a Novel ImageJ Macro.
Background: This study presents a label-free method of separating macrophages and fibroblasts, cell types critically associated with tumors. Materials and Methods: Contactless dielectrophoresis (DEP) devices were used to separate fibroblasts from macrophages by selectively trapping one population. An ImageJ macro was developed to determine the percentage of each population moving or stationary at a given point in time in a video. Results: At 350Vrms, 20 kHz, and 1.25 μL/min, more than 90% of fibroblasts were trapped while less than 20% of macrophages were trapped. Conclusions: Contactless DEP was used to study macrophage and fibroblast separation as a proof-of-concept study for separating cells in the tumor microenvironment. The associated ImageJ macro could be used in other microfluidic cell separation studies.


Influence of substrate on the distribution of calcium channels in identified leech neurons in culture.
The Retzius neuron from the leech, growing in culture on the plant lectin concanavalin A as substrate, produces broad flat growth cones and thick bundles of processes. The same cell extends fine straight processes with numerous branches when grown on a laminin-like substrate extracted from leech central nervous system extracellular matrix, referred to as "leech laminin extract." Cells growing on these two different substrates also show marked differences in the pattern of Ca2+ entry following evoked impulses, as detected optically by local changes in absorbance of the Ca2+-sensitive dye arsenazo III. Ca2+ enters the soma and initial segment of Retzius cells grown on both substrates. However, detectable Ca2+ entry only occurs into the processes of cells growing on leech laminin but not of those growing on concanavalin A. Optical recordings of changes in membrane potential made with the voltage-sensitive dye RH 155 taken from cells growing on either substrate indicate that a depolarization initiated in the soma spreads to the most distant processes with little or no distortion in amplitude or time course. This implies that all voltage-sensitive Ca2+ channels in the cell membrane are equally activated by depolarizing stimuli. Therefore, the fact that impulses evoke Ca2+ entry into processes of Retzius cells grown on leech laminin extract but not of cells grown on concanavalin A shows that the nature of the growth substrate can affect the number and distribution of their functional Ca2+ channels.


Trehalose glycopolymers as excipients for protein stabilization.
Herein, the synthesis of four different trehalose glycopolymers and investigation of their ability to stabilize proteins to heat and lyophilization stress are described. The disaccharide, α,α-trehalose, was modified with a styrenyl acetal, methacrylate acetal, styrenyl ether, or methacrylate moiety resulting in four different monomers. These monomers were then separately polymerized using free radical polymerization with azobisisobutyronitrile (AIBN) as an initiator to synthesize the glycopolymers. Horseradish peroxidase and glucose oxidase were incubated at 70 and 50 °C, respectively, and β-galactosidase was lyophilized multiple times in the presence of various ratios of the polymers or trehalose. The protein activities were subsequently tested and found to be significantly higher when the polymers were present during the stress compared to no additive and to equivalent amounts of trehalose. Different molecular weights (10 kDa, 20 kDa, and 40 kDa) were tested, and all were equivalent in their stabilization ability. However, some subtle differences were observed regarding stabilization ability between the different polymer samples, depending on the stress. Small molecules such as benzyl ether trehalose were not better stabilizers than trehalose, and the trehalose monomer decreased protein activity, suggesting that hydrophobized trehalose was not sufficient and that the polymeric structure was required. In addition, cytotoxicity studies with NIH 3T3 mouse embryonic fibroblast cells, RAW 264.7 murine macrophages, human dermal fibroblasts (HDFs), and human umbilical vein endothelial cells (HUVECs) were conducted with polymer concentrations up to 8 mg/mL. The data showed that all four polymers were noncytotoxic for all tested concentrations. The results together suggest that trehalose glycopolymers are promising as additives to protect proteins from a variety of stressors.


Effects of long-term continuous positive airway pressure on body composition and IGF1.
To investigate the long-term effects of nasal continuous positive airway pressure (CPAP) ventilation in patients with obstructive sleep apnea syndrome (OSAS) on body composition (BC) and IGF1. Observational study. Seventy-eight (11 females and 67 males) OSAS patients who were compliant with CPAP (age 51+/-1.1 years) participated in the study. We assessed body mass index (BMI), total body mass (TBM), total body fat (TBF; kg) and lean body mass (LBM; kg), abdominal subcutaneous (SC) and visceral (V) fat (cm(2)), and waist circumference (WC; cm) by magnetic resonance imaging, and IGF1 (ng/ml) before and after 7.8+/-1.3 months of CPAP use of an average of 5.9+/-1.2 h. Women had a higher BMI, WC; TBM, TBF, and more SC fat. Men had a higher LBM and more V fat. CPAP increased WC (+2.8+/-9.6 cm, P=0.02) and LBM (2.2+/-0.5 kg, P=0.006), but not IGF1. In men, CPAP increased BMI (0.5+/-0.2 kg/m(2), P=0.02), WC (1.7+/-6.9 cm, P=0.002), TBM (1.7+/-0.4 kg, P=0.0001), LBM (1.5+/-0.4 kg, P=0.0003), SC fat (12.9+/-5.1 cm(2), P=0.02), and IGF1 (13.6+/-4.2 ng/ml, P=0.002). Compliance with CPAP increased LBM in men aged <60 years, but not in those aged >60 years, and IGF1 increased in men aged 40-60 years only. Long-term CPAP increased LBM in both sexes and IGF1 in men, while fat mass remained unchanged, suggesting a sexually dimorphic response of IGF1 to CPAP. The role of the GH axis activity and age to this response is unclear. The metabolic consequences of changes in LBM are still to be determined. Future studies on the effects of CPAP on BC should include LBM as an outcome.


A study of treadmill exercise protocols for Chinese males.
Treadmill stress testing currently is used in screening for coronary artery disease. Maximal oxygen consumption is the best index of work capacity and maximal cardiovascular function. Clinically, there are many exercise protocols being utilized, including Bruce, Kattus, Balke, Naughton, and Chinese Air Force (CAF). The purpose of this study is to compare five of them and evaluate their reproducibility. Each of 24 volunteers performed one exercise test per week for 3 periods totalling 15 weeks. During each period, the five different protocols were performed in individually randomized order. Maximal and submaximal oxygen consumption and heart rate were determined. Statistical analysis revealed no difference in maximal oxygen consumption among the various protocols; however significant differences did exist in maximal treadmill time. Maximal exertional duration was not affected by the test periods. All of the five protocols were equally reproducible. The Chinese Air Force has adopted a treadmill protocol with a constant speed of 3.5 mph and a 5% increase in elevation every 3 min. The physiological parameters measured by this protocol include a maximal heart rate of 181 beats/min; maximal oxygen consumption of 48 ml/kg/min; and maximal exercise duration of 17 min. Bruce and Balke protocols were 13 and 24 min, respectively, in our study. The regression equation of oxygen consumption and duration was: Y (ml/kg/min) = 1.26X (min) + 26.3. The CAF protocol is a safe, reproducible, easily performed method with moderate exercise duration. We confirm its advantages and prefer to select this protocol to serve as a routine screening or clinical method for use in testing Chinese people.


Veno-veno-arterial extracorporeal membrane oxygenation for respiratory failure with severe haemodynamic impairment: technique and early outcomes.
Patients with respiratory failure may benefit from veno-venous and veno-arterial extracorporeal membrane oxygenation (ECMO) support. We report on our initial experience of veno-veno-arterial (v-v-a) ECMO in patients with respiratory failure. Between January 2012 and February 2014, 406 patients required ECMO support at our institution. Here, we retrospectively analysed the characteristics and outcomes of patients commenced on either veno-venous or veno-arterial ECMO due to respiratory failure, and then switched to v-v-a ECMO. Ten (2%) patients proceeded to v-v-a ECMO. The underlying conditions were acute respiratory distress syndrome (n = 3), end-stage pulmonary fibrosis (n = 5) and respiratory failure after major thoracic surgery (n = 1) and Caesarean section (n = 1). In all of these patients, ECMO was initially started as veno-venous (n = 9) or veno-arterial (n = 1) ECMO but was switched to a veno-veno-arterial (v-v-a) approach after a mean of 2 (range, 0-7) days. Reasons for switching were: haemodynamic instability (right heart failure, n = 5; pericardial tamponade, n = 1; severe mitral valve regurgitation, n = 1; haemodynamic instability following cardiopulmonary resuscitation, n = 1 and evidence of previously unknown atrial septal defect with pulmonary hypertension and Eisenmenger syndrome, n = 1) and upper-body hypoxaemia (n = 1). ECMO-related complications were bleeding (n = 3) and leg ischaemia (n = 2). Seven patients were successfully taken off ECMO with 4 being bridged to recovery and a further 3 to lung transplantation after a mean of 11 (range, 9-18) days. Five patients survived until hospital discharge and all of them were alive at the end of the follow-up. Veno-veno-arterial ECMO is a technically feasible rescue strategy in treating patients presenting with combined respiratory and haemodynamic failure.


Expression of the progestin-induced fatty acid synthetase in benign mastopathies and breast cancer as measured by RNA in situ hybridization.
We have shown previously that fatty acid synthetase (FAS) is specifically induced by progestins in human breast cancer cell lines. To test the potential value of FAS as a clinical marker in breast diseases, we measured FAS expression in frozen sections of 22 benign and 27 malignant mammary tumors using in situ hybridization with the [35S]UTP alpha S-labeled FAS anti-sense mRNA. The hybridized RNA was quantified with an IMSTAR computerized image analyzer. We found FAS RNA in epithelial cells, but no labeling was detected in the connective tissue. In breast cancer, we found no correlation between FAS expression and estrogen receptor and progesterone receptor concentrations or status. However, the level of FAS was significantly (P less than .02) higher in premenopausal than in post-menopausal patients and increased with the grade of tumor differentiation (P less than .005 between the poorly and well-differentiated tumors). In benign mastopathies, high levels of FAS RNA were found in some cysts (mostly with apocrine metaplasia). In lobules, the FAS RNA level increased proportionally to the degree of proliferation determined by histological examination (P less than .015) and correlated with the H4 histone level measured in an adjacent section using in situ hybridization (r = 0.85, P less than .001). In ductal structures, a lower correlation (r = 0.64, P less than .01) was found between FAS and H4 RNA levels. We conclude that FAS RNA is overexpressed in some mammary tumors and may be useful in predicting high-risk mastopathies and less aggressive breast cancers.


Adaptive visual memory reorganization in right medial temporal lobe epilepsy.
We investigated functional reorganization mechanisms of the human medial temporal lobe (MTL) for episodic memory, in patients suffering from medial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS). We used functional magnetic resonance imaging (fMRI) to measure brain activity changes during matched episodic encoding tasks of abstract words (Verbal) and line drawings (Visual), in patients with unilateral right MTLE undergoing presurgical evaluation and healthy controls. As expected, a significant interaction between material type and the side of MTL activity was present in the control group, with preferential involvement of the left hippocampus in verbal encoding and the right parahippocampal region in visual encoding. When compared with controls, right MTLE patients with intact performance activated a region in the left hippocampus more during visual encoding, which resulted in an interaction between group and hemisphere. Importantly, an effect of memory performance on visual encoding activity was observed in the patients, with greater engagement of the left MTL being associated with higher recognition scores. Interestingly, activity in the left MTL also depended on the epileptic seizure frequency, suggesting a role for this clinical parameter in the recruitment of contralateral regions. Taken together, these results indicate functional reorganization of the MTLs in right HS, through transfer of function from the right to the left hemisphere, and strongly suggest an adaptive role for such reorganization mechanism in supporting preserved visual memory.


N-demethylation of cocaine to norcocaine. Evidence for participation by cytochrome P-450 and FAD-containing monooxygenase.
Experiments were conducted to determine which microsomal enzymes are involved in the in vitro hepatic oxidative N-demethylation of cocaine to norcocaine, the first step in the biotransformation of cocaine to its ultimate hepatotoxic metabolite. Cocaine was found to undergo conversion to norcocaine by two alternate pathways, one involving only cytochrome P-450 and the other requiring both cytochrome P-450 and FAD-containing monooxygenase. In the first pathway, cocaine was directly N-demethylated to norcocaine by cytochrome P-450; this reaction was enhanced by phenobarbital induction and was inhibited by both n-octylamine and metyrapone. The second route was found to be a two-step reaction involving cocaine N-oxide as an intermediate. In this pathway, cocaine is first oxidized to cocaine N-oxide by FAD-containing monooxygenase, followed by a cytochrome P-450-catalyzed N-demethylation to norcocaine. This latter step was enhanced by phenobarbital treatment and inhibited by n-octylamine. Cocaine N-oxide also exhibited a Type I binding spectrum with mouse hepatic microsomes. In addition, a model system consisting of ferrous sulfate was found to catalyze the N-demethylation of cocaine N-oxide. On the basis of these experiments, it is concluded that cytochrome P-450 and FAD-containing monooxygenase participate in the initial oxidation of cocaine to norcocaine. We also propose a mechanism to account for the conversion of cocaine N-oxide to norcocaine.


ITAlian partnership for psychosis prevention (ITAPP): Improving the mental health of young people.
The European impact of the clinical high risk for psychosis (CHR-P) paradigm is constrained by the lack of critical mass (detection) to power prognostic and preventive interventions. An ITAlian partnership for psychosis prevention (ITAPP) was created across CHR-P centers, which were surveyed to describe: (a) service, catchment area, and outreach; (b) service users; and (c) interventions and outcomes. Descriptive statistics and Kaplan-Meier failure function complemented the analyses. The ITAPP included five CHR-P clinical academic centers established from 2007 to 2018, serving about 13 million inhabitants, with a recruitment capacity of 277 CHR-P individuals (mean age: 18.7 years, SD: 4.8, range: 12-39 years; 53.1% females; 85.7% meeting attenuated psychotic symptoms; 85.8% without any substance abuse). All centers were multidisciplinary and included adolescents and young adults (transitional) primarily recruited through healthcare services. The comprehensive assessment of at-risk mental state was the most widely used instrument, while the duration of follow-up, type of outreach, and preventive interventions were heterogeneous. Across 205 CHR-P individuals with follow up (663.7 days ± 551.7), the cumulative risk of psychosis increased from 8.7% (95% CI 5.3-14.1) at 1 year to 15.9% (95% CI 10.6-23.3) at 2 years, 21.8% (95% CI 14.9-31.3) at 3 years, 34.8% (95% CI 24.5-47.9) at 4 years, and 51.9% (95% CI 36.3-69.6) at 5 years. The ITAPP is one of the few CHR-P clinical research partnerships in Europe for fostering detection, prognosis, and preventive care, as well as for translating research innovations into practice.


Diagnosis of childhood pneumonia in the tropics.
Recent global estimates indicate that there are 10 million deaths annually of children aged < 5 years and that 99% of these deaths occur in developing countries, with 70% caused by infections. Pneumonia is the leading cause of the infection-attributable mortality in this age-group, accounting for > 2 million of the deaths. These deaths are potentially preventable if appropriate clinical and laboratory tools are in place to facilitate early detection of the pneumonia, identification of the pathogen involved, and institution of appropriate therapy or, even better, implementation of appropriate vaccination schedules. The currently available tools for the diagnosis of acute, lower-respiratory-tract infections in children have low sensitivity and are, in any case, grossly underutilized. Consequently, there is a great shortage of the data necessary for implementing potentially effective, intervention measures. This review is of the common aetiological agents of childhood pneumonia in the tropics and of the clinical and laboratory techniques currently available for routine diagnosis. Although there are newer and more sensitive diagnostic tools, they are expensive and are not likely to be within reach of most developing countries in the tropics. There is, however, considerable scope to improve the use of the cheaper techniques, and so facilitate the development and implementation of effective control measures.


Preparation and evaluation of GAC-based iron-containing adsorbents for arsenic removal.
Granular activated carbon-based, iron-containing adsorbents (As-GAC) were developed for effective removal of arsenic from drinking water. Granular activated carbon (GAC) was used primarily as a supporting medium for ferric iron that was impregnated by ferrous chloride (FeCl2) treatment, followed by chemical oxidation. Sodium hypochlorite (NaClO) was the most effective oxidant, and carbons produced from steam activation of lignite were most suitable for iron impregnation and arsenic removal. Two As-GAC materials prepared by FeCl2 treatment (0.025 -0.40 M) of Dacro 20 x 50 and Dacro 20 x 40LI resulted in a maximum impregnated iron of 7.89% for Dacro 20 x 50 and 7.65% for Dacro 20 x 40Ll. Nitrogen adsorption-desorption analyses showed the BET specific surface area, total pore volume, porosity, and average mesoporous diameter all decreased with iron impregnation, indicating that some micropores were blocked. SEM studies with associated EDS indicated that the distribution of iron in the adsorbents was mainly on the edge of As-GAC in the low iron content (approximately 1% Fe) sample but extended to the center at the higher iron content (approximately 6% Fe). When the iron content was > approximately 7%, an iron ring formed at the edge of the GAC particles. No difference in X-ray diffraction patterns was observed between untreated GAC and the one with 4.12% iron, suggesting that the impregnated iron was predominantly in amorphous form. As-GAC could remove arsenic most efficiently when the iron content was approximately 6%; further increases of iron decreased arsenic adsorption. The removal of arsenate occurred in a wide range of pH as examined from 4.4 to 11, but efficiency was decreased when pH was higher than 9.0. The presence of phosphate and silicate could significantly decrease arsenate removal at pH > 8.5, while the effects of sulfate, chloride, and fluoride were minimal. Column studies showed that both As(V) and As(III) could be removed to below 10 microg/L within 6000 empty bed volume when the groundwater containing approximately 50 microg/L of arsenic was treated.


PI3K (Phosphatidylinositol 3-Kinase) Activation and Endothelial Cell Proliferation in Patients with Hemorrhagic Hereditary Telangiectasia Type 1.
Hemorrhagic hereditary telangiectasia (HHT) type 2 patients have increased activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in telangiectasia. The main objective is to evaluate the activation of the PI3K pathway in cutaneous telangiectasia of HHT1 patients. A cutaneous biopsy of a digital hand telangiectasia was performed in seven HHT1 and eight HHT2 patients and compared with six controls. The study was approved by the Clinical Research Ethics Committee of our center. A histopathological pattern with more dilated and superficial vessels that pushed up the epidermis was identified in HHT patients regardless of the type of mutation and was associated with older age, as opposed to the common telangiectasia pattern. The mean proliferation index (Ki-67) was statistically higher in endothelial cells (EC) from HHT1 than in controls. The percentage of positive EC for pNDRG1, pAKT, and pS6 in HHT1 patients versus controls resulted in higher values, statistically significant for pNDRG1 and pS6. In conclusion, we detected an increase in EC proliferation linked to overactivation of the PI3K pathway in cutaneous telangiectasia biopsies from HHT1 patients. Our results suggest that PI3K inhibitors could be used as novel therapeutic agents for HHT.


Toward a better understanding of the infrageneric relationships in Cortinarius (Agaricales, Basidiomycota).
Research on the molecular systematics of Cortinarius, a species-rich mushroom genus with nearly global distribution, is just beginning. The present study explores infrageneric relationships using rDNA ITS and LSU sequence data. One large dataset of 132 rDNA ITS sequences and one combined da-taset with 54 rDNA ITS and LSU sequences were generated. Hebeloma was used as outgroup. Bayesian analyses and maximum-likelihood (ML) analyses were carried out. Bayesian phylogenetic inference performed equally well or better than ML, especially in large datasets. The phylogenetic analysis of the combined dataset with species representing all currently recognized subgenera recovered seven well-supported clades (Bayesian posterior probabilities BPP > 90%). These major clades are: /Myxacium s.l., /subg. Cortinarius, the /phlegmacioid clade (including the subclades /Phlegmacium and /Delibuti), the /calochroid clade (/Calochroi, /Ochroleuci and /Allutus), the /telamonioid clade (/Telamonia, /Orellani, /Anomali), /Dermocybe s.l. and /Myxotelamonia. Our results show that Cortinarius consists of many lineages, but the relationships among these clades could not be elucidated. On one hand, the low divergence in rDNA sequences can be held responsible for this; on the other hand, taxon sampling is problematic in Cortinarius phylogeny. Because of the incredibly high diversity (~2000 Cortinarius species), our sampling included <5% of the known species. By choosing type species of subgenera and sections, our sampling is strongly biased toward Northern Hemisphere taxa. More extensive taxon sampling, especially of species from the Southern Hemisphere, is essential to resolve the phylogeny of this important genus of ectomycorrhizal fungi.


Resident dendritic cells are the predominant TNF-secreting cell in early renal ischemia-reperfusion injury.
Renal ischemia-reperfusion injury (IRI) rapidly induces production of inflammatory mediators including, and in particular, tumor necrosis factor (TNF). Possible sources include resident parenchymal and bone marrow-derived cells as well as recruited leukocytes. Cell suspensions from kidneys subjected to IRI were examined by cell separation followed by in vitro culture and enzyme-linked immunosorbent assay (ELISA), immunoperoxidase and immunofluorescence microscopy, and multicolor flow cytometry to determine the contribution of dendritic cells (DCs) to early production of TNF and other inflammatory mediators. Secretion of TNF, interleukin (IL-6), monocyte chemoattractant protein-1 (MCP-1), and regulated on activation normal T cell expressed and secreted (RANTES) was increased in cell suspensions from IRI compared with control kidneys and was higher in DC-enriched preparations. Immunostaining identified TNF(+ve) cells that coexpressed the DC marker CD11c. Flow cytometry of bone marrow-derived (CD45(+ve)) cell populations at 24 h post-IRI demonstrated that F4/80(+ve)/CD11c(+ve) DCs remained proportionately stable and exhibit higher levels of DC maturation markers, whereas the proportion of F4/80(-ve) DCs, monocytes, neutrophils, and T cells increased. Intracellular staining for TNF confirmed that F4/80(+ve) DCs were the predominant TNF(+ve) cell and expressed higher levels than other TNF(+ve) cells. In vivo depletion of DCs from the kidney substantially attenuated TNF secretion by total and CD45(+ve) cells following IRI. The results uncover a role for resident F4/80(+ve) DCs as the predominant secretors of TNF within 24 h of IRI.


[Constructing the meaning of breast feeding through nursing care].
From the referential of Symbolic Interactionism and Dada Based Theory we have searched to achieve the objectives of comprehending the meaning, attributed by the nursing student to breastfeeding and to nursing interventions in this process. The study was accomplished with graduation students from Sao Paulo University (USP) Nursing School. The study results show that the student experience his relation to breastfeeding and to his learning process in assisting the nutrice and her child expressed by two themes: BUILDING UP A VIEW OVER BREASTFEEDING and BUILDING UP ASSISTANCE TO BREASTFEEDING. These themes portrait students' conceptual and technical evolutive process about breastfeeding assistance and their perception of being a nurse, attributing meanings to their performance in the process that is experienced by woman and her child.


Mimicking descending necrotizing mediastinitis as acute myocardial infarction in a patient with severe coronary artery disease: A case report.
It is a crucial disease that descending necrotizing mediastinitis need to be treated promptly with proper antibiotics and drainage. The characteristics of its symptoms such as chest pain are difficult to distinguish from acute myocardial infarction. An 80-year-old female presented with severe squeezing chest pain. The cardiac marker was elevated. And coronary angiography showed the significant coronary stenosis. Although the revascularization through percutaneous coronary intervention was completed successfully, the patient still presented chest pain. Computed tomography of neck revealed that hypodense heterogeneous lesions with clear and distinguishable margin extended from the deep neck to mediastinum diffusely. The patient was diagnosed with descending necrotizing mediastinitis. Percutaneous catheter insertion to patient's abscess lesion at was performed. Catheter drainage of descending necrotizing mediastinitis led to an improvement in the patient's condition. Descending necrotizing mediastinitis made chest paint with elevated cardiac enzyme mimicked myocardial infarction.


[Clinical value of the antioxidative activity of blood serum and lacrimal fluid in endogenous uveitis in children].
The method of chemiluminescence in the system of hemoglobin-peroxide hydrogen-luminal was made use of to study the antioxidant activity (AOA) of lacrimal fluid and blood serum in 20 children with endogenous uveitis. As uveitis aggravated, there is observed a reduced AOA both in lacrimal fluid and blood serum. As the inflammatory process is arrested, AOA begins to go down gradually; moreover, it approaches the values in the control group. The correlation between the lacrimal fluid AOA and the blood serum AOA was calculated and analyzed for each eye for the moment of examination. The low values of the coefficient were found for the constantly relapsing uveitis, while the high values were typical for the initial remission phase. A study of the correlation between the blood serum AOA and the lacrimal fluid AOA showed a low correlation coefficient (r = 0.3) during the uveitis aggravation period and its increase during the remission period (r = 0.7). The obtained data are indicative of that the free-radical processes are involved in the pathogenesis of endogenous uveitis; they also show that it is advisable to study the lacrimal-fluid and blood-serum AOAs in order to forecast the above disease and to choose an optimal therapy methods.


An automated measurement system for characterization of RF and gradient coil parameters.
A fully automated laboratory-based measurement system for characterization of coil system parameters is presented. This method uses an inexpensive personal computer (PC)-controlled stepper motor positioning system in conjunction with a network/spectrum analyzer and an analog-to-digital converter (A/D) board that allows high resolution data acquisition in an unattended manner. A graphical interface was created for complete control of stepper motor movement, measurement, and data acquisition. The system is capable of performing a wide range of measurements that can, either individually or combined, characterize radiofrequency (RF) and gradient coils used in MRI. Measurement methods, theory, and results for conductor and shield current distributions, mutual impedance, and magnetic fields are given. Comparisons with theoretical calculations are included to validate the accuracy and utility of the system.


The microbial eukaryote Blastocystis is a prevalent and diverse member of the healthy human gut microbiota.
To date, the majority of research into the human gut microbiota has focused on the bacterial fraction of the community. Inevitably, this has resulted in a poor understanding of the diversity and functionality of other intestinal microorganisms in the human gut. One such nonbacterial member is the microbial eukaryote Blastocystis, which has been implicated in the aetiology of a range of different intestinal and extra-intestinal diseases. However, prevalence data from different studies are conflicting, and crucially, there is limited information on its incidence and diversity in healthy individuals. Here, we survey the prevalence, genetic diversity and temporal stability of Blastocystis in a group of healthy adults (n = 105) using a sensitive PCR assay. Blastocystis was present in 56% of our sample set, which is much higher than previously reported from an industrialised county (Ireland). Moreover, a diversity of different subtypes (species) were detected, and Blastocystis was present in a subset of individuals sampled over a period of time between 6 and 10 years, indicating that it is capable of long-term host colonisation. These results show that Blastocystis is a common and diverse member of the healthy gut microbiota, thereby extending our knowledge of the microbial ecology of the healthy human intestine.


Differential ligand selectivity of androgen receptors α and β from Murray-Darling rainbowfish (Melanotaenia fluviatilis).
Androgen receptors (ARs) mediate the physiological effects of androgens in vertebrates. In fishes, AR-mediated pathways can be modulated by aquatic contaminants, resulting in the masculinisation of female fish or diminished secondary sex characteristics in males. The Murray-Darling rainbowfish (Melanotaenia fluviatilis) is a small-bodied freshwater teleost used in Australia as a test species for environmental toxicology research. We determined concentration-response profiles for selected agonists and antagonists of rainbowfish ARα and ARβ using transient transactivation assays. For both ARα and ARβ, the order of potency of natural agonists was 11-ketotestosterone (11-KT)>5α-dihydrotestosterone>testosterone>androstenedione. Methyltestosterone was a highly potent agonist of both receptors relative to 11-KT. The relative potency of the veterinary growth-promoting androgen, 17β-trenbolone, varied by more than a factor of 5 between ARα and ARβ. The non-steroidal anti-androgen bicalutamide exhibited high inhibitory potency relative to the structurally related model anti-androgen, flutamide. The inhibitory potency of the agricultural fungicide, vinclozolin, was approximately 1.7-fold relative to flutamide for ARα, but over 20-fold in the case of ARβ. Fluorescent protein tagging of ARs showed that the rainbowfish ARα subtype is constitutively localised to the nucleus, while ARβ is cytoplasmic in the absence of ligand, an observation which agrees with the reported subcellular localisation of AR subtypes from other teleost species. Collectively, these data suggest that M. fluviatilis ARα and ARβ respond differently to environmental AR modulators and that in vivo sensitivity to contaminants may depend on the tissue distribution of the AR subtypes at the time of exposure.


[Experience of vitamin K2 in Thailand].
Vitamin K(2) has dual actions, stimulates osteoblastic functions, for synthesis of osteocalcin, osteonectin and other matrix bone proteins, in addition, new finding, in stem cell culture found osteoblast producing gene expression of collagen type 1, the other action, vitamin K(2) contains mild antiresorpion by inducing the osteoclastic apoptosis. Our study found that postmenopausal and elderly women have high risk of vitamin K(2) deficiency, comparing to the normal value of young, reproductive females. The efficacy of vitamin K(2) will be fulfill benefit after 6 months of administration, prolong use will enhance of bone quality that prevent fracture.


The role of computed tomography in the assessment of dental disease in 66 guinea pigs.
Sixty-six guinea pigs with dental disease were presented to the University of Veterinary Medicine, Vienna, Austria, from 2006 to 2010. Almost all patients had a history of eating difficulties (95 per cent) and underwent clinical and oral examination as well as CT of the head. Findings on extra- and intraoral examination were asymmetric elongation (n=28) and symmetric bridging (n=24) of cheek teeth, obliquely worn incisors (n=17), palpable lower jaw swellings (n=13), exophthalmos (n=10) and incisor macrodontia (n=6). Eighty per cent of guinea pigs with exophthalmos showed ipsilateral periapical disease of the maxillary cheek teeth on CT. Ninety-two per cent of patients with palpable lower jaw swellings showed corresponding dental pathologies on CT. Periapical disease of incisors (n=11) and cheek teeth (n=32) were the most common findings on CT. All abnormally large incisors were found on oral examination and CT, but macrodontia of cheek teeth could only be visualised by CT. Deviation of the lower jaw evaluated in awake animals by visual inspection appeared to correlate with cheek teeth abnormalities. Results emphasise the importance of diagnostic imaging, in particular CT, in guinea pigs with dental disease in order to localise lesions and underlying aetiologies.


Risk of Colorectal Cancer in Chronic Kidney Disease: A Systematic Review and Meta-Analysis.
Association between chronic kidney disease and colorectal cancer (CRC) remains unclear. To assess the risk of CRC in patients with various chronic kidney diseases before and after kidney transplantation. Electronic databases were searched for cohort studies assessing the risk of CRC in patients with chronic kidney diseases. The primary outcome was the risk of CRC among studies that reported the risk as standardized incidence rate (SIR). Fifty-four studies, including 1,208,767 patients that reported the incidence of CRC in chronic kidney diseases were identified. SIR of CRC were obtained from 17 retrospective cohort studies. Among the 3 studies (4 reports) that included chronic kidney disease patients without kidney transplantation, there was a significant increased risk of CRC (pooled SIR 1.18) (95% confidence interval, 1.01-1.37; P=0.033). High heterogeneity was seen (I=85.6%), and metaregression showed that there were positive correlations between the risk of CRC and the proportions of males, age and follow-up period. Among the 15 studies (17 reports) that included postkidney transplant patients, the pooled SIR was significantly increased at 1.40 (95% confidence interval, 1.15-1.71; P=0.00080). High heterogeneity was seen (I=88.9%), and metaregression showed that the follow-up period correlated with the risk of CRC. In the present systematic review and meta-analysis, we demonstrated that patients with chronic kidney disease, regardless of a history of transplant, have a significant increased risk of CRC. A more intensive surveillance for CRC is required in this population.


Transtympanic Sodium Thiosulfate for Prevention of Cisplatin-Induced Ototoxicity: A Randomized Clinical Trial.
To determine safety, feasibility, and preliminary activity of transtympanic injection of sodium thiosulfate (STS) against cisplatin-induced hearing loss (CIHL).DESIGN Randomized controlled trial.SETTING Tertiary cancer hospital.PATIENTS Adults to be treated with high-dose cisplatin (≥ 75 mg/m2).INTERVENTION Selected by randomization, 0.1 M STS gel on one side and placebo gel on the other side was transtympanically applied to the middle ear 3 hours before cisplatin administration. After amendment, the placebo ear was left untreated. Primary outcome was safety and feasibility. Secondary outcomes included pharmacokinetic analysis of systemic cisplatin and preliminary activity of STS. Clinically relevant CIHL was defined as a ≥ 10 dB threshold shift at pure-tone average 8-10-12.5 kHz (PTA8-12.5). Response to STS was defined as a threshold shift at PTA8-12.5 in the STS-treated ear of ≥ 10 dB smaller than the untreated ear. Twelve patients were treated. Average CIHL at PTA8-12.5 was 12.7 dB in untreated ears and 8.8 dB SPL in STS-treated ears (p = 0.403). Four patients did not develop CIHL. Four out of eight patients with CIHL responded to STS: CIHL at PTA8-12.5 in STS-treated ears was 18.4 dB less compared to untreated ears (p = 0.068). Grade 1 adverse events were reported. Pharmacokinetic results were available for 11 patients. Transtympanic application of STS was safe and feasible. Based on our pharmacokinetic analysis, we postulate that transtympanic STS does not interfere with the systemically available cisplatin. Our results provide a preliminary proof of concept for transtympanic application of STS in preventing CIHL and warrants further evaluation on a larger scale.


Towards the evolution of the mHealth in mental health with youth: the cyber-space used in psychological rehabilitation is becoming wearable into a pocket.
The study is focused into the field of tele-mental health with youth. It has three polarities. The first polarity consists on the analysis of the state of art of the guide-lines and reports the recent situation depicted by the American Telemedicine Association and the American Psychiatric Association. The second polarity faces the recent evolution related to the tools available in mHealth to activate remote psychological rehabilitation processes. These tools are today also based on a wearable cyberspace comprehending virtual (VR) and augmented reality (AR). The third polarity concludes the study by opening and submitting basic questions on the related activity of the stake-holders, scholars, regulation bodies and workgroups and showing some example of this activity.


Highly structured homolog pairing reflects functional organization of the Drosophila genome.
Trans-homolog interactions have been studied extensively in Drosophila, where homologs are paired in somatic cells and transvection is prevalent. Nevertheless, the detailed structure of pairing and its functional impact have not been thoroughly investigated. Accordingly, we generated a diploid cell line from divergent parents and applied haplotype-resolved Hi-C, showing that homologs pair with varying precision genome-wide, in addition to establishing trans-homolog domains and compartments. We also elucidate the structure of pairing with unprecedented detail, observing significant variation across the genome and revealing at least two forms of pairing: tight pairing, spanning contiguous small domains, and loose pairing, consisting of single larger domains. Strikingly, active genomic regions (A-type compartments, active chromatin, expressed genes) correlated with tight pairing, suggesting that pairing has a functional implication genome-wide. Finally, using RNAi and haplotype-resolved Hi-C, we show that disruption of pairing-promoting factors results in global changes in pairing, including the disruption of some interaction peaks.


Reflections on a visit to a dementia care village.
Hogewey village in Holland offers an alternative lifestyle for people with dementia. The model minimises disability and maximises wellbeing by providing a physical and social environment congruent with people's lifestyles. Residents live with those who have shared similar previous lifestyles and take an active role in all aspects of daily life, reflecting their interests and social norms. The village is staffed by healthcare professionals and well-supported volunteers, who promote personhood in small social groups and facilitate normal life. The authors explore how this approach contrasts with those used in the UK and draw conclusions about applying the model in the UK. They believe that healthcare professionals can learn from the Dutch example and adapt existing environments to reflect some of the concepts that are applied successfully at Hogewey. Well-supported volunteers, integrated into teams, could take on the role of supportive friends rather than clinically orientated problem-solvers and help to reintegrate people with dementia into local communities.


Norwegian remote sensing experiment in a marginal ice zone.
The Norwegian Remote Sensing Experiment in the marginal ice zone north of Svalbard took place in fall 1979. Coordinated passive and active microwave measurements were obtained from shipborne, airborne, and satellite instruments together with in situ observations. The obtained spectra of emissivity (frequency range, 5 to 100 gigahertz) should improve identification of ice types and estimates of ice concentration. Mesoscale features along the ice edge were revealed by a 1.215-gigahertz synthetic aperture radar. Ice edge location by the Nimbus 7 scanning multichannel microwave radiometer was shown to be accurate to within 10 kilometers.


A national profile of school-based transition programs for deaf adolescents.
In this study, the transition programs of 326 secondary educational programs for deaf and severely hearing-impaired adolescents were surveyed. Three types of programs were surveyed: residential, mainstream, and "other" (a combination of the first two programs). Sixty-four items depicting desirable transition characteristics were included in the survey, and each item was rated by the programs on a value scale and an implementation scale. Analyses of variance were calculated to determine if there were statistically significant differences among the three program types for each individual survey item on the two rating scales. Based on the data, it appears that the residential schools had higher implementation rates than the mainstream and other programs. All three respondent groups valued the transition items more than they had implemented them (i.e., the value scores were higher than the implementation scores). The data point out the need for researchers and educators to develop and implement more effective transition programs for deaf and severely hearing-impaired students.