Effects of the Solvent Vapor Exposure on the Optical Properties and Photocatalytic Behavior of Cellulose Acetate/Perylene Free-Standing Films.
The search to deliver added value to industrialized biobased materials, such as cellulose derivatives, is a relevant aspect in the scientific, technological and innovation fields at present. To address these aspects, films of cellulose acetate (CA) and a perylene derivative (Pr) were fabricated using a solution-casting method with two different compositions. Consequently, these samples were exposed to dimethylformamide (DMF) solvent vapors so that its influence on the optical, wettability, and topographical properties of the films could be examined. The results demonstrated that solvent vapor could induce the apparent total or partial preferential orientation/migration of Pr toward the polymer-air interface. In addition, photocatalytic activities of the non-exposed and DMF vapor-exposed films against the degradation of methylene blue (MB) in an aqueous medium using light-emitting diode visible light irradiation were comparatively investigated. Apparently, the observed improvement in the performance of these materials in the MB photodegradation process is closely linked to the treatment with solvent vapor. Results from this study have allowed us to propose the fabrication and use of the improved photoactivity "all-organic" materials for potential applications in dye photodegradation in aqueous media.


Two Poems. Genetic Lottery. Work of Art.
The following poems are an autoethnographic account of body image from the perspective of a 39-year-old bountiful, White-privileged, mixed-race femme dyke. The purpose of the poetic form is to inspire emotional connection and offer analytic commentary on the social construction of body image, aging, and beauty as a social commodity, from a lesbian perspective. Together, the poems present a perspective on lesbian body image that highlights our socialization as women first. Lesbian consciousness has a role in how we construct body image outside of a primarily male gaze, but it does not supplant heteronormative feminity. The poems also show the critical social gaze as reconstructed within us and by our lovers. In addition to social influences, the poems also show the life of the individual as a site of body image activism. The agency of "I' to reconstruct interactions of body acceptance and self-love is as clear as the contexts in which those struggles take place.


[Obstructive jaundice caused by metastasis to the head of the pancreas by a malignant melanoma].
We report on a 68-year-old patient who developed an obstructive jaundice 13 years after surgery of a malignant melanoma of the right ear. The initial sonographic and CT diagnosis of a benign pseudocyst of the head of the pancreas had to be revised based on ERCP, sonographically guided puncture and papillary biopsy. By Whipple's procedure, the solitary intrapancreatic metastasis could be successfully removed.


Three-Dimensional (3D) Printed Silver Nanoparticles/Alginate/Nanocrystalline Cellulose Hydrogels: Study of the Antimicrobial and Cytotoxicity Efficacy.
Here, a formulation of silver nanoparticles (AgNPs) and two natural polymers such as alginate (ALG) and nanocrystalline cellulose (CNC) was developed for the 3D printing of scaffolds with large surface area, improved mechanical resistance and sustained capabilities to promote antimicrobial and cytotoxic effects. Mechanical resistance, water content, morphological characterization and silver distribution of the scaffolds were provided. As for applications, a comparable antimicrobial potency against S. aureus and P. aeruginosa was demonstrated by in vitro tests as function of the AgNP concentration in the scaffold (Minimal Inhibitory Concentration value: 10 mg/mL). By reusing the 3D system the antimicrobial efficacy was demonstrated over at least three applications. The cytotoxicity effects caused by administration of AgNPs to hepatocellular carcinoma (HepG2) cell culture through ALG and ALG/CNC scaffold were discussed as a function of time and dose. Finally, the liquid chromatography-mass spectrometry (LC-MS) technique was used for targeted analysis of pro-apoptotic initiation and executioner caspases, anti-apoptotic and proliferative proteins and the hepatocyte growth factor, and provided insights about molecular mechanisms involved in cell death induction.


[Isolation and expression profiling of the Pto-like gene SsPto from Solanum surattense].
A novel Pto-like gene (designated as SsPto) is cloned from yellow-fruit nightshade (Solanum surattense). The full-length cDNA of SsPto is 1331 bp long with an open reading frame of 960 bp encoding a polypeptide of 320 amino acid residues. The deduced SsPto protein has a calculated molecular weight of 36.21 kDa with an isoelectric point of 6.18. Multiple sequence alignment shows that SsPto protein shares 71.4% and 71.6% identities to Pto proteins from Lycopersicon pimpinellifolium and L. hirsutum respectively. Genomic Southern blot analysis indicates the presence of a small family of SsPto in the S. surattense genome. SsPto is found to be constitutively expressed in the S. surattense plant with the highest expression in stems. However, under induction by TMV for 6 days, SsPto expresses the highest in roots. Further expression analysis reveals that the signaling components of defense/stress pathways, such as methyl jasmonate (MeJA), salicylic acid (SA), gibberellic acid (GA3) and hydrogen peroxide (H2O2), up-regulate the SsPto transcript levels over the control. Cold treatment, nevertheless, has no significant effect on SsPto expression whereas SsPto expression is down-regulated by dark treatment. Our findings suggest that this novel stress- and pathogen-inducible SsPto from S. surattense may participate not only in the defense/stress responsive pathways, but also in diverse processes of plant's growth and development.


[Changes of the mitochondrial DNA copy number and the antioxidant system in the PBMC of hepatocellular carcinoma].
To investigate the relationship between the changes of the copy numbers of mtDNA in peripheral blood mono-nucle- ar cell(PBMC) and the disordered of antioxidant capacity of hepatocellular carcinoma (HCC) patients. The Ficoll Hypaque method was used to isolate the PBMC from blood specimens. The ND1 gene of the mitochondrial was amplified by real-time PCR; meantime β-actin was served as a quantitative standard marker; the difference of mtDNA copy number in PBMC was compared between HCC and healthy control group. The level of reactive oxygen species (ROS) in PBMC was determined by flow cytometry. The change of total antioxidant capacity (T- AOC) of plasma was detected by the biochemistry examination. The copy numbers of ND1 gene in PBMC of HCC was 73% that of the healthy control group,which suggested a decrease of the copy numbers of mtDNA in HCC. The levels of ROS of PBMC in HCC was (417. 82 ± 110.62) and (301.82 ± 75.54) in control group, which showed that the levels of ROS of PBMC in HCC were significant higher than that in control group (P < 0.01).Plasma T-AOC in HCC was (1.30 ± 0.85), and (3.20 ± 1.62) in control. The T-AOC of plasma of HCC was significantly lower than in control group (P < 0.01). There was a certain relationship between the decrease of the copy numbers of mtDNA and the disordered antioxidant capacity in hepatocellular carcinoma, which may be associated with the development of hepatocellular carcinoma.


Clostridium difficile Exposures, Colonization, and the Microbiome: Implications for Prevention.
New studies have been published regarding the epidemiology of Clostridium difficile in topics such as asymptomatic C. difficile colonization, community-associated C. difficile infection, environmental contamination outside healthcare settings, animal colonization, and the interactions between C. difficile and the gut microbiome. In addition to summarizing these findings, this review offers a perspective on the potential impact of high-throughput sequencing and other potential techniques on the prevention of C. difficile.Infect Control Hosp Epidemiol 2018;39:596-602.


Renal kinetics in acute heart failure.
Worsening renal function (WRF) in acute heart failure (AHF) has multifactorial pathophysiological mechanisms and heterogeneous prognostic impacts. The aim of this study was to determine the characteristics and renal kinetics of this phenomenon. We prospectively enrolled a cohort of 196 patients admitted for AHF to the Cardiology Department at Nhan Dan Gia Dinh Hospital, from July 2016 to March 2017. AHF was defined using the 2012 European Society of Cardiology criteria. The definition and severity of WRF were based on the 2012 Kidney Disease Improving Outcome criteria for acute kidney injury. Renal recovery was classified using the 2017 Acute Disease Quality Initiative 16 Workgroup Consensus. Among the 196 patients studied, WRF developed in 43.4%. In 80.0% of patients, WRF occurred within 48 hours of admission. In the WRF group, 89.4% were at stage 1, consistent with a relative increase in median serum creatinine of 49.5%. A total of 76.5% of the patients with WRF recovered at discharge, while rapid recovery occurred in 20.0% of patients. Most cases of WRF were mild, and WRF was correlated with a high rate of recovery during hospitalisation. However, rapid renal recovery was not common.


A context-aware-based audio guidance system for blind people using a multimodal profile model.
A wearable guidance system is designed to provide context-dependent guidance messages to blind people while they traverse local pathways. The system is composed of three parts: moving scene analysis, walking context estimation and audio message delivery. The combination of a downward-pointing laser scanner and a camera is used to solve the challenging problem of moving scene analysis. By integrating laser data profiles and image edge profiles, a multimodal profile model is constructed to estimate jointly the ground plane, object locations and object types, by using a Bayesian network. The outputs of the moving scene analysis are further employed to estimate the walking context, which is defined as a fuzzy safety level that is inferred through a fuzzy logic model. Depending on the estimated walking context, the audio messages that best suit the current context are delivered to the user in a flexible manner. The proposed system is tested under various local pathway scenes, and the results confirm its efficiency in assisting blind people to attain autonomous mobility.


Grasslands: A Source of Secondary Metabolites for Livestock Health.
The need for environmentally friendly practices in animal husbandry, in conjunction with the reduction of the use of synthetic chemicals, leads us to reconsider our agricultural production systems. In that context, grassland secondary metabolites (GSMs) could offer an alternative way to support to livestock health. In fact, grasslands, especially those with high dicotyledonous plant species, present a large, pharmacologically active reservoir of secondary metabolites (e.g., phenolic compounds, alkaloids, saponins, terpenoids, carotenoids, and quinones). These molecules have activities that could improve or deteriorate health and production. This Review presents the main families of GSMs and uses examples to describe their known impact on animal health in husbandry. Techniques involved for their study are also described. A particular focus is put on anti-oxidant activities of GSMs. In fact, numerous husbandry pathologies, such as inflammation, are linked to oxidative stress and can be managed by a diet rich in anti-oxidants. The different approaches and techniques used to evaluate grassland quality for livestock health highlight the lack of efficient and reliable technics to study the activities of this complex phytococktail. Better knowledge and management of this animal health resource constitute a new multidisciplinary research field and a challenge to maintain and valorize grasslands.


Packing Defects in Fatty Amine Self-Assembled Monolayers on Mica as Revealed from AFM Techniques.
Self-assembled monolayers of n-octadecylamine (ODA-SAMs) on mica have been prepared and studied by contact and jumping mode atomic force microscopy (AFM). Adhesion and friction data show that the compactness of the monolayers spontaneously increases as they are allowed to ripen. Molecular packing can also be induced by the controlled mechanical perturbation exerted by the probe when getting into and out of contact intermittently. Under these conditions, defects and vacancies aggregate giving rise to detectable pinholes uniformly distributed in AFM images. Created pinhole density was found to decrease with ripening time, thus confirming the proposed spontaneous self-healing mechanism. Pinhole density is also suggested as a parameter characterizing the packing degree of ODA-SAMs, and it has been related to their tribological properties. Additionally, molecular dynamics simulations were used to corroborate the compatibility between the packing degree and the observed topography of ODA-SAMs on mica.


HOTAIR promotes gefitinib resistance through modification of EZH2 and silencing p16 and p21 in non-small cell lung cancer.
The long non-coding RNA Hox transcript antisense intergenic RNA (HOTAIR) plays a critical role in tumorigenesis as well as drug resistance in various cancers. However, the molecular mechanism by which HOTAIR induces gefitinib resistance in non-small cell lung cancer is to date unclear. In the present study, we revealed that HOTAIR is upregulated in gefitinib-resistant lung cancer cells and over-expression of HOTAIR enhances gefitinib resistance in lung cancer cells. In addition, the overexpression of HOTAIR promotes cell cycle progression through epigenetic regulation of EZH2/H3K27. Silencing of EZH2 by either siRNA or inhibitors sensitized the lung cancer cells to gefitinib. Inhibition of EZH2 induces expression of p16 and p21, whereas levels of CDK4, cyclinD1, E2F1, and LSD1 are significantly decreased in PC-9 cells overexpressing HOTAIR. ChIP-PCR experiments indicate that HOTAIR increases H3K27me3 recruitment to the promoter of p16 and p21 in PC-9 lung cancer cells overexpressing HOTAIR. In xenograft mouse models, overexpressing HOTAIR in lung cancer tissues decreased p16 and p21 proteins. Taken together, these data suggest that HOTAIR contributes to gefitinib resistance by regulating EZH2 and p16 and p21. Targeting HOTAIR may be a novel therapeutic strategy for treating gefitinib-resistance in non-small cell lung cancer.


Room-temperature vibrational difference spectrum for S2QB-/S1QB of photosystem II determined by time-resolved Fourier transform infrared spectroscopy.
Time-resolved FTIR spectroscopy has been used to kinetically characterize the vibrational properties of intact photosystem II-enriched membrane samples undergoing the S1QB-to-S2QB- transition at room temperature. To optimize the experimental conditions for the FTIR measurements, oxygen polarographic and variable chlorophyll a fluorescence measurements were used to define the decay of S2 and QA-, respectively. The flash-induced S2QB-/S1QB difference spectra were measured at a temporal resolution of 4.44 s and a spectral resolution of 4 cm-1. An intense positive band is observed at 1480 cm-1 in the difference spectrum and shows a slow decay with a half time of approximately 13 s. Based on its decay kinetics and analogy to the infrared absorption of QA- of photosystem II and QB- in bacterial reaction centers, we conclude that the 1480 cm-1 band arises from QB- of PSII and tentatively assign it to the upsilon(CO) mode of the semiquinone anion QB-. The infrared spectral features attributed to the S1-to-S2 transition of the Mn cluster at room temperature show striking similarity to the S2/S1 difference spectrum measured at cryogenic temperatures (Noguchi, T., Ono, T.-A., and Inoue, Y. (1995) Biochim. Biophys. Acta 1228, 189-200).


H. PYLORI INFECTION, ENDOSCOPIC, HISTOLOGICAL ASPECTS AND CELL PROLIFERATION IN THE GASTRIC MUCOSA OF PATIENTS SUBMITTED TO ROUX-EN-Y GASTRIC BYPASS WITH CONTENTION RING: a cross sectional endoscopic and immunohistochemical study.
Morbid obesity treatment through vertical gastroplasty Roux-en-Y gastric bypass initially used a contention ring. However, this technique may create conditions to the development of potentially malign alterations in the gastric mucosa. Although effective and previously performed in large scale, this technique needs to be better evaluated in long-term studies regarding alterations caused in the gastric mucosa. To analyze the preoperative and postoperative endoscopic, histological and cell proliferation findings in the gastric antrum and body mucosa of patients submitted to the Roux-en-Y gastric bypass with a contention ring. We retrospectively evaluated all patients submitted to Roux-en-Y gastric bypass with a contention ring with more than 60 months of postoperative follow-up. We compared the preoperative (gastric antrum and body) and postoperative (gastric pouch) gastric mucosa endoscopic findings, cell proliferation index and H. pylori prevalence. We evaluated cell proliferation through Ki-67 antibody immunohistochemical expression. In the study period, 33 patients were operated with the Roux-en-Y gastric bypass using a contention ring. We found a chronic gastritis rate of 69.7% in the preoperative period (gastric antrum and body) and 84.8% in the postoperative (gastric pouch). H. pylori was present in 18.2% of patients in the preoperative period (gastric antrum and body) and in 57.5% in the postoperative (gastric pouch). Preoperative cell proliferation index was 18.1% in the gastric antrum and 16.2% in the gastric body, and 23.8% in the postoperative gastric pouch. The postoperative cell proliferation index in the gastric pouch was significantly higher (P=0.001) than in the preoperative gastric antrum and body. Higher cell proliferation index and chronic gastritis intensity were significantly associated to H. pylori presence (P=0.001 and P=0.02, respectively). After Roux-en-Y gastric bypass with contention ring, there was a higher chronic gastritis incidence and higher cell proliferation index in the gastric pouch than in the preoperative gastric antrum and body. Mucosa inflammation intensity and cell proliferation index in the postoperative gastric pouch were associated to H. pylori presence and were higher than those found in the preoperative gastric antrum and body mucosa.


Fractional urinary clearance of immunoreactive lipase in chronic pancreatic disease.
Using an immunoenzymatic method, we studied lipase in the serum and urine of 23 controls, 22 chronic pancreatitis patients in symptomatic remission, and in 9 patients with proven pancreatic cancer. Serum and urine lipase and its fractional urinary clearance were compared with those of amylase and immunoreactive trypsin. Lipase immunoreactivity was detectable in the urine of 81.5% of the studied subjects (controls: 82%, chronic pancreatitis: 86%, pancreatic cancer: 66%); its output was higher than the upper limit of controls in 31.8% of chronic pancreatitis and in only 1 of pancreatic cancer, and it was significantly correlated with the urinary output of trypsin (r = 0.487, P less than 0.001), but not with that of amylase. A significant correlation was found between urinary output and serum levels for lipase, but not for trypsin or amylase. Fractional clearance of lipase was of the same magnitude as that of trypsin but only 0.1% that of amylase. 19% of chronic pancreatitis and pancreatic cancer showed a fractional clearance of lipase above the upper limit of controls, compared with 45% for trypsin and 3.2% for amylase. No difference in urinary clearance of the three enzymes was found between chronic pancreatitis and pancreatic cancer. In conclusion, although of no diagnostic relevance in pain-free patients with chronic pancreatic disease, this measurement can provide information on the mechanisms of renal excretion of pancreatic enzymes.


Effective matching of patients to clinical trials using entity extraction and neural re-ranking.
Clinical trials (CTs) often fail due to inadequate patient recruitment. Finding eligible patients involves comparing the patient's information with the CT eligibility criteria. Automated patient matching offers the promise of improving the process, yet the main difficulties of CT retrieval lie in the semantic complexity of matching unstructured patient descriptions with semi-structured, multi-field CT documents and in capturing the meaning of negation coming from the eligibility criteria. This paper tackles the challenges of CT retrieval by presenting an approach that addresses the patient-to-trials paradigm. Our approach involves two key components in a pipeline-based model: (i) a data enrichment technique for enhancing both queries and documents during the first retrieval stage, and (ii) a novel re-ranking schema that uses a Transformer network in a setup adapted to this task by leveraging the structure of the CT documents. We use named entity recognition and negation detection in both patient description and the eligibility section of CTs. We further classify patient descriptions and CT eligibility criteria into current, past, and family medical conditions. This extracted information is used to boost the importance of disease and drug mentions in both query and index for lexical retrieval. Furthermore, we propose a two-step training schema for the Transformer network used to re-rank the results from the lexical retrieval. The first step focuses on matching patient information with the descriptive sections of trials, while the second step aims to determine eligibility by matching patient information with the criteria section. Our findings indicate that the inclusion criteria section of the CT has a great influence on the relevance score in lexical models, and that the enrichment techniques for queries and documents improve the retrieval of relevant trials. The re-ranking strategy, based on our training schema, consistently enhances CT retrieval and shows improved performance by 15% in terms of precision at retrieving eligible trials. The results of our experiments suggest the benefit of making use of extracted entities. Moreover, our proposed re-ranking schema shows promising effectiveness compared to larger neural models, even with limited training data. These findings offer valuable insights for improving methods for retrieval of clinical documents.


Recent Progress in Crystalline Borates with Edge-Sharing BO4 Tetrahedra.
Crystalline borates have received great attention due to their various structures and wide applications. For a long time, the corner-sharing B-O unit is considered a basic rule in borate structural chemistry. The Dy4B6O15 synthesized under high-pressure is the first oxoborate with edge-sharing [BO4] tetrahedra, while the KZnB3O6 is the first ambient pressure borate with the edge-sharing [BO4] tetrahedra. The edge-sharing connection modes greatly enrich the structural chemistry of borates and are expected to expand new applications in the future. In this review, we summarize the recent progress in crystalline borates with edge-sharing [BO4] tetrahedra. We discuss the synthesis, fundamental building blocks, structural features, and possible applications of these edge-sharing borates. Finally, we also discuss the future perspectives in this field.


Induction of antibody response by antigen conjugates and E. coli lipopolysaccharide in mice tolerant to dextran B-512.
Three groups of mice were made tolerant to dextran (Dex) with one of three schedules: a) an immunogenic dose of 10 micrograms three times a week for 26 weeks; b) an immunogenic dose of 50 micrograms three times a week for two weeks, and c) a single tolerogenic dose of 10 mg. Prior to tolerance induction, continuous administration of 10 micrograms Dex induced a predominantly IgM antibody response. The tolerant mice were then challenged with immunogenic doses of the dextran conjugates Dex-Salmonella typhi (Dex-S. typhi) and Dex-sheep red blood cells (Dex-SRBC), and with E. coli lipopolysaccharide (LPS). IgM and IgG responses were compared in each group. Immunogenic dextran alone did not induce a response in the 1 tolerant mice. The response induced by Dex-S. typhi or Dex-SRBC was low but LPS induced an elevated anti-Dex SFC in the three groups of resistant mice. The antibody responses were not affected by pretreatment of antigen with dextranase. Loss of tolerance was more pronounced in mice made tolerant by continuous stimulation as compared to mice made tolerant by a single large dose of antigen. Thus, LPS is able to induce specific responses from B cells of tolerant animals. Furthermore, the level of response was dependent on the toleration schedule.


The prevalence of malaria in Garki, Nigeria: double sampling with a fallible expert.
Data from the Garki Project are analyzed to assess how misdiagnosis affects the estimated prevalence of Plasmodium falciparum. Three double-sampling models that account for the fallibility of the expert are derived and applied. The models incorporate information about the density of parasites in the blood to varying degrees. The error in the estimation of prevalence is quantified; and its dependence on calendar time, age, prevalence, and density is investigated. Prevalence and average density are discovered to be good predictors of the error, with the latter being better. Implications of the double-sampling models for the design of epidemiological surveys similar to the one in Garki are investigated.


Polygenic Adaptation and Clonal Interference Enable Sustained Diversity in Experimental Pseudomonas aeruginosa Populations.
How biodiversity arises and can be maintained in asexual microbial populations growing on a single resource remains unclear. Many models presume that beneficial genotypes will outgrow others and purge variation via selective sweeps. Environmental structure like that found in biofilms, which are associated with persistence during infection and other stressful conditions, may oppose this process and preserve variation. We tested this hypothesis by evolving Pseudomonas aeruginosa populations in biofilm-promoting arginine media for 3 months, using both a bead model of the biofilm life cycle and planktonic serial transfer. Surprisingly, adaptation and diversification were mostly uninterrupted by fixation events that eliminate diversity, with hundreds of mutations maintained at intermediate frequencies. The exceptions included genotypes with mutator alleles that also accelerated genetic diversification. Despite the rarity of hard sweeps, a remarkable 40 genes acquired parallel mutations in both treatments and often among competing genotypes within a population. These incomplete soft sweeps include several transporters (including pitA, pntB, nosD, and pchF) suggesting adaptation to the growth media that becomes highly alkaline during growth. Further, genes involved in signal transduction (including gacS, aer2, bdlA, and PA14_71750) reflect likely adaptations to biofilm-inducing conditions. Contrary to evolution experiments that select mutations in a few genes, these results suggest that some environments may expose a larger fraction of the genome and select for many adaptations at once. Thus, even growth on a sole carbon source can lead to persistent genetic and phenotypic variation despite strong selection that would normally purge diversity.


Environmental and Nutritional Determinants of Macular Pigment in a Mexican Population.
The carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin deposit at the macula as macular pigment (MP) and provide visual benefits and protection against macular diseases. The present study investigated MP, its nutritional and environmental determinants, and its constituent carotenoids in serum from a Mexican sample, in healthy participants and with metabolic diseases. Additionally, we compared these variables with an Irish sample. MP was measured in 215 subjects from a rural community in Mexico with dual-wavelength autofluorescence imaging reported as MP optical volume (MPOV). Dietary intake and serum concentrations of L and Z were evaluated. The mean MPOV was 8429 (95% confidence interval, 8060-8797); range. 1171-15,976. The mean L and Z serum concentrations were 0.25 ± 0.15 µmol/L and 0.09 ± 0.04 µmol/L, respectively. The MPOV was positively correlated with L and Z serum concentrations (r = 0.347; P < 0.001 and r = 0.311; P < 0.001, respectively), but not with L + Z dietary estimates. Subjects with daily sunlight exposure of more than 50% were found to have significantly higher MPOV than those with less than 50% (P = 0.005). MPOV and serum concentrations of L and Z were significantly higher in the Mexican sample compared with the Irish sample, but this difference was not reflected in dietary analysis. These new data from a Mexican sample provide evidence of the multifactorial interactions and environmental determinants of MP such as sunlight exposure and dietary patterns. These findings will be essential for future studies in Mexico for eye health, visual function, and ocular pathology.


Psychological and Behavioral Impact of Participation in Ovarian Cancer Screening.
Evaluation of costs and benefits associated with cancer screening should include consideration of any psychological and behavioral impact associated with screening participation. Research examining the psychological and behavioral impact of screening asymptomatic women for ovarian cancer (OC) was considered. Research has focused upon potential negative psychological (e.g., distress) and behavioral (e.g., reduced future screening participation) impact of false positive (FP) OC test results. Results suggest FP OC screening results are associated with greater short-term OC-specific distress. While distress dissipates over time it may remain elevated relative to pre-screening levels for several weeks or months even after clinical follow-up has ruled out malignancy. The likelihood of participation in future OC screening may also be reduced. Research focused upon identification of any beneficial impact of participation in OC screening associated with receipt of "normal" results was also considered. This research suggests that a "normal" screening test result can have psychological benefits, including increased positive affect and beliefs in the efficacy of screening. It is concluded that any psychological or behavioral harms attributable to OC screening are generally very modest in severity and duration and might be counterbalanced by psychological benefits accruing to women who participate in routine OC screening and receive normal test results.


Cognitive Impairment in Neuromyelitis Optica Spectrum Disorders: A Review of Clinical and Neuroradiological Features.
Neuromyelitis optica spectrum disorders (NMOSD) are mostly relapsing autoimmune inflammatory disorders of the central nervous system (CNS) with optic neuritis, myelitis, and brainstem syndromes as clinical hallmarks. With a reported prevalence of up to 70%, cognitive impairment is frequent, but often unrecognized and an insufficiently treated burden of the disease. The most common cognitive dysfunctions are decline in attention and memory performance. Magnetic resonance imaging can be used to access structural correlates of neuropsychological disorders. Cognitive impairment is not only a highly underestimated symptom in patients with NMOSD, but potentially also a clinical correlate of attack-independent changes in NMOSD, which are currently under debate. This article reviews cognitive impairment in NMOSD and discusses associations between structural changes of the CNS and cognitive deficits.


Cardiac sympathetic nerve biology and brain monoamine turnover in panic disorder.
Panic disorder serves as a clinical model for testing whether mental stress can cause heart disease. Our own cardiologic management of panic disorder provides case material of recurrent emergency room attendances with angina and electrocardiogram ischemia, triggered arrhythmias (atrial fibrillation, ventricular fibrillation), and documented coronary artery spasm, in some cases with coronary spasm being complicated by coronary thrombosis. Application of radiotracer catecholamine kinetics and clinical microneurography methodology suggests there is a genetic predisposition to panic disorder that involves faulty neuronal norepinephrine uptake, possibly sensitizing the heart to symptom generation. During panic attacks there are large sympathetic bursts, recorded by clinical microneurography in the muscle sympathetic nerve neurogram, and large increases in cardiac norepinephrine spillover, accompanied by surges of adrenal medullary epinephrine secretion. In other conditions such as heart failure and presumably here also, a high level of sympathetic nervous activation can mediate increased cardiac risk. The sympathetic nerve cotransmitter, neuropeptide Y (NPY), is released from the cardiac sympathetics during panic attacks, an intriguing finding given that NPY can cause coronary artery spasm. There is ongoing, continuous release of epinephrine from the heart in panic sufferers, perhaps attributable to epinephrine loading of cardiac sympathetic nerves by uptake from plasma during panic attacks, or possibly to in situ synthesis of epinephrine through the action of intracardiac phenylethanolamine-N-methytransferase (PNMT) activated by repeated cortisol responses. We have used internal jugular venous sampling and measurement of overflowing lipophilic brain monoamine metabolites to quantify brain norepinephrine and serotonin turnover in untreated patients with panic disorder. We find normal norepinephrine turnover but a marked increase in brain serotonin turnover in patients with panic disorder, in the absence of a panic attack, which presumably represents an underlying neurotransmitter substrate for the condition.


[Polymorphism of regulated upon activation, normal T cell expressed and secreted promoter region -28 position in Chinese allergic asthmatic children].
To study the effect of regulated upon activation, normal T cell expressed and secreted (RANTES)-28 polymorphism on allergic asthma in Chinese children. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify the polymorphism at position -28 of the RANTES promoter in 100 asthmatic children (group A). Levels of plasma IgE and RANTES were detected by chemiluminescence and ELISA respectively. The number of peripheral eosinophils was counted. Data were compared with those of the control group of 90 healthy children (group B). (1) Both C allele and G allele were detected at -28 of the RANTES promoter; the prevalence of the G allele in group A was 19.5%, as compared to 10.6% in group B; the prevalence of RANTES-28G allele was significantly different between the two groups (P < 0.05). (2) For genotypes C/C, C/G and G/G in asthmatics, levels of plasma RANTES were (289 +/- 199) ng/L, (515 +/- 119) ng/L and (1 071 +/- 138) ng/L, respectively, the difference being significant among the three genotypes (P < 0.01). (3) For genotypes C/C, C/G and G/G in asthmatics, total levels of plasma IgE (lg IgE) were 2.45 +/- 0.12, 2.77 +/- 0.07 and 3.16 +/- 0.09, respectively, the difference being not significant among the three genotypes (P > 0.05). (4) The numbers of peripheral eosinophils were (2.9 +/- 1.4) x 10(8)/L, (6.4 +/- 0.8) x 10(8)/L and (9.9 +/- 2.3) x 10(8)/L in genotypes C/C, C/G and G/G in asthmatics respectively, and the difference being significant among the three genotypes (P < 0.01). Polymorphism of RANTES C-28G was associated with susceptibility of asthma in children, and may aggravate the disease through increasing the level of RANTES and eosinophils.


Antibodies to MuMTV proteins in the sera of mammary carcinoma patients' healthy daughters.
The presence of antibodies to MuMTV-related proteins in sera of 31 mammary carcinoma patients' healthy daughters have been tested by indirect immunoperoxidase method (ELISA). Ten of them (32.3 +/- 8.4%) reacted with MuMTV proteins preparations, but not with MuLV, RaLV, SSV, MPMV proteins or preparations of mouse embryonic tissues. The percent of positive sera in this group is almost ten times higher than among women without breast cancer in family history (earlier published data). By immunoblotting method the specificity for five positive sera was determined. Two sera react with p27, one with p27 and to a less extent with gp52, one-only with gp52 and one more serum with both proteins equally. Mothers of the daughters with positive-reacted sera were characterized by premenopausal tumors, detected on early (I, IIa) clinical stage of disease.


Ammoniibacillus agariperforans gen. nov., sp. nov., a thermophilic, agar-degrading bacterium isolated from compost.
A thermophilic, agar-degrading bacterium, strain FAB2(T), was isolated from sewage sludge compost. According to phylogenetic analysis based on 16S rRNA gene sequences, strain FAB2(T) belonged to the family Paenibacillaceae within the phylum Firmicutes. However, FAB2(T) was different enough at the genus level from closely related species. The percentages of 16S rRNA gene sequence similarity with related organisms were 90.4 % for Thermobacillus xylanilyticus, 91.8 % for Paenibacillus barengoltzii, 89.4 % for Cohnella lupini, 90.1 % for Fontibacillus aquaticus, and 89.0 % for Saccharibacillus sacchari. Morphological and physiological analyses revealed that the strain was motile, rod-shaped, Gram-stain-positive, aerobic and able to form oval endospores in swollen sporangia. Ammonium was required as a nitrogen source while nitrate, nitrite, urea and glutamate were not utilized. Catalase and oxidase activities were weakly positive and positive, respectively. The bacterium grew in the temperature range of 50-65 °C and in media with pH 7.5 to 9.0. Optimal growth occurred at 60 °C and pH 8.0-8.6. Growth was inhibited at pH≤7.0 and NaCl concentrations ≥2.5 % (w/v). In chemotaxonomic characterization, MK-7 was identified as the dominant menaquinone. Major fatty acids were iso-C16 : 0 and C16 : 0. Dominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Phosphatidylcholine was present in a moderate amount. The diamino acid in the cell wall was meso-diaminopimelic acid. The G+C content of the genomic DNA was 49.5 mol% in a nucleic acid study. On the basis of genetic and phenotypic characteristics, strain FAB2(T) ( = NBRC 109510(T) = KCTC 33130(T)) showed characteristics suitable for classification as the type strain of a novel species of a new genus in the family Paenibacillaceae, for which the name Ammoniibacillus agariperforans gen. nov., sp. nov. is proposed.


Brachypodium as an experimental system for the study of stem parenchyma biology in grasses.
Stem parenchyma is a major cell type that serves key metabolic functions for the plant especially in large grasses, such as sugarcane and sweet sorghum, where it serves to store sucrose or other products of photosynthesis. It is therefore desirable to understand the metabolism of this cell type as well as the mechanisms by which it provides its function for the rest of the plant. Ultimately, this information can be used to selectively manipulate this cell type in a controlled manner to achieve crop improvement. In this study, we show that Brachypodium distachyon is a useful model system for stem pith parenchyma biology. Brachypodium can be grown under condition where it resembles the growth patterns of important crops in that it produces large amounts of stem material with the lower leaves senescing and with significant stores of photosynthate located in the stem parenchyma cell types. We further characterize stem plastid morphology as a function of tissue types, as this organelle is central for a number of metabolic pathways, and quantify gene expression for the four main classes of starch biosynthetic genes. Notably, we find several of these genes differentially regulated between stem and leaf. These studies show, consistent with other grasses, that the stem functions as a specialized storage compartment in Brachypodium.


The Effect of Long-Pulsed Nd:YAG Laser for the Treatment of Onychomycosis.
Topical onychomycosis therapies are usually inadequate, and patient compliance to systemic therapies is poor. Recently, interest in laser therapy for the treatment of onychomycosis has increased. We sought to investigate the efficacy of long-pulsed Nd:YAG laser therapy for onychomycosis. Thirty patients with mycologically confirmed onychomycosis received long-pulsed 1064-nm Nd:YAG laser therapy, moving the beam in a spiral pattern over the whole nail plate two times, with a 1-minute pause between passes. Laser therapy was performed with a spot diameter of 4 mm at a speed of 25 mm/sec once weekly for 4 weeks using fluencies ranging from 40 to 60 J/cm2, depending on the thickness of the nail plate. Patients were evaluated in terms of clinical improvement and mycologic cure. Thirty patients started and 15 completed the study. Mycologic cure was achieved in nine patients (60%), of whom eight (89%) were infected with Trichophyton sp. Complete clinical improvement was achieved in seven patients (47%), all of whom were infected with Trichophyton sp. Mycologic cure was not achieved in one of two patients infected with Epidermophyton or in either patient in whom the agent was Candida or Aspergillus; complete clinical improvement did not occur in any of these patients. No serious adverse events were observed. Based on these results, long-pulsed Nd:YAG laser can be used as an effective treatment for onychomycosis, but further studies are needed to draw firmer conclusions.


Cholesterol Efflux Drives the Generation of Immunosuppressive Macrophages to Promote the Progression of Human Hepatocellular Carcinoma.
Cholesterol is often enriched in tumor microenvironment (TME); however, its impact on disease progression varies in different tissues and cells. Monocytes/macrophages (Mφ) are major components and regulators of the TME and play pivotal roles in tumor progression and therapeutic responses. We aimed to investigate the profile, effects, and regulatory mechanisms of Mφ cholesterol metabolism in the context of human hepatocellular carcinoma (HCC). Here, we found that patients with high serum levels of cholesterol had shorter survival times and lower response rates to anti-PD-1 treatment. However, the cholesterol content in tumor-infiltrating monocytes/Mφ was significantly lower than that in their counterparts in paired nontumor tissues. The expression of the cholesterol efflux transporter, ABCA1, was upregulated in tumor monocytes/Mφ, and ABCA1 upregulation positively associated with decreased cellular cholesterol content and increased serum cholesterol levels. Mechanistically, autocrine cytokines from tumor-treated monocytes increased LXRα and ABCA1 expression, which led to the generation of immature and immunosuppressive Mφ. Although exogenous cholesterol alone had little direct effect on Mφ, it did act synergistically with tumor-derived factors to promote ABCA1 expression in Mφ with more immunosuppressive features. Moreover, high numbers of ABCA1+ Mφ in HCC tumors associated with reduced CD8+ T-cell infiltration and predicted poor clinical outcome for patients. Our results revealed that dysregulated cholesterol homeostasis, due to the collaborative effects of tumors and exogenous cholesterol, drives the generation of immunosuppressive Mφ. The selective modulation of cholesterol metabolism in Mφ may represent a novel strategy for cancer treatment.


Differential responses of rabbit ventricular and atrial transient outward current (Ito) to the Ito modulator NS5806.
Transient outward potassium current (Ito) in the heart underlies phase 1 repolarization of cardiac action potentials and thereby affects excitation-contraction coupling. Small molecule activators of Ito may therefore offer novel treatments for cardiac dysfunction, including heart failure and atrial fibrillation. NS5806 has been identified as a prototypic activator of canine Ito This study investigated, for the first time, actions of NS5806 on rabbit atrial and ventricular Ito Whole cell patch-clamp recordings of Ito and action potentials were made at physiological temperature from rabbit ventricular and atrial myocytes. 10 μmol/L NS5806 increased ventricular Ito with a leftward shift in Ito activation and accelerated restitution. At higher concentrations, stimulation of Ito was followed by inhibition. The EC50 for stimulation was 1.6 μmol/L and inhibition had an IC50 of 40.7 μmol/L. NS5806 only inhibited atrial Ito (IC50 of 18 μmol/L) and produced a modest leftward shifts in Ito activation and inactivation, without an effect on restitution. 10 μmol/L NS5806 shortened ventricular action potential duration (APD) at APD20-APD90 but prolonged atrial APD NS5806 also reduced atrial AP upstroke and amplitude, consistent with an additional atrio-selective effect on Na+ channels. In contrast to NS5806, flecainide, which discriminates between Kv1.4 and 4.x channels, produced similar levels of inhibition of ventricular and atrial Ito NS5806 discriminates between rabbit ventricular and atrial Ito, with mixed activator and inhibitor actions on the former and inhibitor actions against the later. NS5806 may be of significant value for pharmacological interrogation of regional differences in native cardiac Ito.


Glucose-Responsive Polyelectrolyte Complexes Based on Dendritic Mesoporous Silica for Oral Insulin Delivery.
The postprandial glycemic regulation is essential for diabetic patients to reduce the risk of long-term microvascular and macrovascular complications. Herein, we designed a glucose-responsive oral insulin delivery system based on polyelectrolyte complexes (PECs) for controlling the increasing postprandial glucose concentrations. Briefly, alginate-g-3-aminophenylboronic acid (ALG-g-APBA) and chitosan-g-3-fluoro-4-carboxyphenylboronic acid (CS-g-FPBA) were wrapped on mesoporous silica (MSN) to form the negative charged ALG-g-APBA@MSN and the positive charged CS-g-FPBA@MSN nanoparticles, with an optimum insulin loading capacity of 124 mg/g and 295 mg/g, respectively. ALG-g-APBA@MSN was further cross-linked with CS-g-FPBA@MSN to form PECs through electrostatic interaction and borate esters. The dense polyelectrolyte network wrapped on MSN was capable of preventing insulin from diffusion and regulating its release. The in vitro insulin release of PECs demonstrated an obvious glucose response profile in different glucose concentrations (0 mg/mL, 2 mg/mL, 5 mg/mL) and presented a switch "on" and "off" release regulation at hyperglycemic or normal state. The CCK-8 assay showed that none of the MSN, ALG-g-APBA@MSN, CS-g-FPBA@MSN, and PECs possessed cytotoxicity to Caco-2 cells. For in vivo tests, the oral PECs exhibited a significant hypoglycemic effect and maintained in the euglycemic levels up to approximately 12 h on diabetic rats. Overall, the PECs directly triggered by postprandial glucose in the intestine have a good potential to be applied in intelligent insulin delivery by the oral route.


Human delta-aminolevulinate dehydratase: chromosomal localization to 9q34 by in situ hybridization.
The structural gene for human delta-aminolevulinate dehydratase (ALA-D) has been localized to chromosomal region 9q34 by in situ hybridization using a [125I]-labeled human delta-aminolevulinate dehydratase cDNA. Of the 150 silver grains analyzed, 25% were localized to chromosome 9q, while 12% and 8% were on chromosomes 1p and 13q, respectively. The single chromosomal region q34 had over 90% of the total grains observed on chromosome 9. In contrast, the grains on chromosomes 1p and 13q were dispersed, consistent with the absence of any human ALA-D pseudogenes. Southern blot analysis of somatic cell hybrids informative for ALA-D (Wang et al. 1985) also was consistent and supported the finding of only one locus for this heme biosynthetic enzyme.


Fructose Feeding during the Postabsorptive State Alters Body Composition and Spares Nitrogen in Protein-Energy-Restricted Old Rats.
Fructose feeding in the context of high energy intake is recognized as being responsible for metabolic dysregulation. However, its consumption in the postabsorptive state might contribute to reducing the use of amino acids (AAs) as energy substrates and thus spare nitrogen resources, which could be beneficial during catabolic states. We hypothesized that fructose feeding during a catabolic situation corresponding to protein-energy restriction (PER) in older rats would reduce AA utilization for energy purposes, thus slowing down the loss of body weight (BW) and improving body composition. For 45 d, 22-mo-old male Wistar rats (average weight: 716 g) were fed a control ration (13% protein) either at normal (20 g/d), restricted (PER: 10 g/d), or at PER levels supplemented with glucose (3 g/d) or fructose (3 g/d) and then studied in the postabsorptive state. We measured BW, body composition, and enzyme activities and metabolite concentrations related to glucose, fructose, and AA metabolism. Both glucose and fructose feeding reduced PER-induced loss of BW and lean mass (-27% compared with PER), but only fructose reduced the loss of fat mass (-28% compared with PER). Fructose feeding prevented the PER-induced loss of muscle and intestinal mass. Fructose feeding also reduced circulating branched-chain AA concentrations by 50% (compared with PER) and increased those of alanine (+65% compared with PER). A reduction in hepatic enzymes related to AA catabolism was also observed during fructose feeding (compared with PER), whereas glycogen concentrations were enhanced in both intestine (+300%) and muscle (+21%). We showed that in PER older rats, fructose feeding improved body composition and the weight of several organs by reducing AA catabolism and utilization for energy production and liver autophagy potential. This could be advantageous in sparing body proteins, particularly during catabolic states, such as those related to malnutrition during aging.


The Proxy Step-Size Technique for Regularized Optimization on the Sphere Manifold.
We give an effective solution to the regularized optimization problem g (x) + h (x), where x is constrained on the unit sphere ||x ||2 = 1. Here g (·) is a smooth cost with Lipschitz continuous gradient within the unit ball {x : ||x ||2 ≤ 1 } whereas h (·) is typically non-smooth but convex and absolutely homogeneous, e.g., norm regularizers and their combinations. Our solution is based on the Riemannian proximal gradient, using an idea we call proxy step-size - a scalar variable which we prove is monotone with respect to the actual step-size within an interval. The proxy step-size exists ubiquitously for convex and absolutely homogeneous h(·), and decides the actual step-size and the tangent update in closed-form, thus the complete proximal gradient iteration. Based on these insights, we design a Riemannian proximal gradient method using the proxy step-size. We prove that our method converges to a critical point, guided by a line-search technique based on the g(·) cost only. The proposed method can be implemented in a couple of lines of code. We show its usefulness by applying nuclear norm, l1 norm, and nuclear-spectral norm regularization to three classical computer vision problems. The improvements are consistent and backed by numerical experiments. available at https://bitbucket.org/FangBai/proxystepsize-pgs.


In vitro biocompatibility of hydroxyapatite-added GIC: An SEM study using human periodontal ligament fibroblasts.
Nano-hydroxyapatite-added GIC has been developed to improve the physical properties of conventional GIC. However, biological response of periodontal cells to this potentially useful cervical restorative material has been unexplored. The aim of this study was to investigate the in vitro response of human periodontal ligament fibroblasts to hydroxyapatite-added GIC. Three categories of materials, namely, test group 1 (cGIC or type IX GIC), test group 2 (HA-GIC or hydroxyapatite-added GIC), and positive control (glass cover slips) were incubated with human periodontal ligament fibroblasts. The samples were viewed under scanning electron microscope to study the morphological characteristics of fibroblasts. Additionally, elemental analysis was performed to differentiate between the two test groups based on surface chemical composition. Test group 1 (cGIC) exhibited cells with curled up morphology, indicative of poor attachment to the substrate. Test group 2 (Ha-GIC) exhibited cells with flattened morphology and numerous cellular extensions such as lamellipodia and blebs, indicative of good attachment to the substrate. The test group 2 (Ha-GIC) demonstrated higher surface elemental percentages of calcium and phosphorus. Within the limitations of this study, it may be concluded that hydroxyapatite-added GIC is more biocompatible than conventional GIC (type IX), probably attributed to high elemental percentages of calcium and phosphorus. The search for an ideal cervical restorative dental material has been ever elusive. Hydroxyapatite-added GIC is a simple and economical dental material to fabricate from basic conventional GIC. The results from this study strengthen its candidature for cervical and root surface restorations which may later require soft tissue augmentation. The possibility of connective tissue adhesion to this material is an exciting prospect in the field of periorestorative dentistry.


Associations of hypertensive disorders of pregnancy with cognition, dementia, and brain structure: a Mendelian randomization study.
Observational studies have found associations between hypertensive disorders of pregnancy and an increased risk of cognitive dysfunction and reduced brain volume. However, the results of observational studies may have been influenced by confounding factors. This study applied two-sample Mendelian randomization (MR) to explore the causal associations of hypertensive disorders of pregnancy with cognition, dementia, and brain structure. Summary data on hypertensive disorders of pregnancy and their main subtypes, cognition, dementia, and brain structure were obtained from recent European genome-wide association studies. We computed the inverse-variance weighted, MR-Egger, and weighted median MR estimates. Cochran's Q statistics and the MR-Egger intercept test were used to quantify the heterogeneity and horizontal pleiotropy of the instrumental variables. Genetically predicted preeclampsia or eclampsia was inversely associated with gray matter volume [beta = -0.072; 95% confidence interval (CI) = -0.131 to -0.014; P = 1.53 × 10-2]; possibly with brain volume (beta = -0.064; 95% CI = -0.117 to -0.012; P = 1.68 × 10-2). However, the association of hypertensive pregnancy disorders or gestational hypertension with brain structure was not significant. We did not find any significant association between hypertensive disorders of pregnancy, gestational hypertension, or preeclampsia or eclampsia and cognition and dementia-related outcomes. This study provided genetic evidence supporting an association between preeclampsia or eclampsia and reduced brain volume. This supports the view of PE as a risk factor for gray matter volume reduction.


Bilateral retrobulbar hemorrhage and visual loss following traumatic asphyxia.
Retrobulbar hemorrhage and permanent visual loss are rare presentations following traumatic asphyxia. In this case, bilateral permanent visual disturbance developed in a woman after chest-crushing trauma without direct trauma to the orbits. A computed tomography scan confirmed bilateral retrobulbar hemorrhages. An ophthalmologic exam revealed bilateral subconjunctival hemorrhages and severe lid edema. Despite high-dose steroid therapy, visual recovery was limited, and optic nerve atrophy developed. Ischemia of the optic nerve associated with retrobulbar hemorrhage may be postulated as one of the causes of permanent visual impairment following traumatic asphyxia.


[Vaccinations for immunocompromised hosts – focussing on patients after a hematological stem cell or organ transplantation, with HIV or with functional or anatomical asplenia].
Patients with an acquired immune deficiency, for example due to HIV-infection, after a solid organ or haematological stem cell transplantation or due to functional or anatomical asplenia, have a greater risk to experience severe complications or a chronic course of infection compared to healthy individuals. Vaccinations would pose an ideal primary preventive method. However, their efficacy is reduced if applied during the immunosuppressed period. Therefore, whenever possible, vaccinations should be administered before the period of immunosuppression starts – or caught up later during the period of minimal possible immunosuppression. Nevertheless, the benefit conveyed through vaccines is undisputed, particularly if indications regarding dosing of vaccines (amount and frequency of doses) are optimized according to the given state of immunosuppression. Live attenuated vaccines are contraindicated during severe immunosuppression. Serologies should still be analysed and documented however, since these vulnerable patients require passive immunization through specific or standard intravenous immunoglobulins in case of relevant exposure to the respective antigens. For all patients therefore, careful documentation and communication of previous vaccinations and serologies (protective or not) among the various medical specialties is required to optimize patient management. For all immunosuppressed patients the efficacy of polysaccharide vaccines (such as the pneumococcal and meningococcal vaccines PSV-23 and MPV-ACWY) is strongly reduced compared to the conjugated ones (PCV13 and MCV-ACWY). Therefore, contrary to most other national guidelines, the Swiss guidelines recommend to use only the conjugated versions in primary vaccination series as well as in boosters – this applies strongly for immunosuppressed patients, but is recommended also for the general population in Switzerland. Another common management recommendation specific for transplant patients is the indication to control vaccine efficacy by measuring titers. This is also indicated for hepatitis B in HIV-positive patients, but not required for any vaccine in asplenic patients. In summary, vaccines pose an important opportunity for primary and secondary prevention for vulnerable patients at highest risk of experiencing the worst forms of the diseases to be prevented.


Physical aggression during early childhood: trajectories and predictors.
This study aimed to identify the trajectories of physical aggression during early childhood and antecedents of high levels of physical aggression early in life. 572 families with a 5-month-old newborn were recruited. Assessments of physical aggression frequency were obtained from mothers at 17, 30, and 42 months after birth. Using a semiparametric mixture model and multivariate logit regression analyses, distinct clusters of physical aggression trajectories were identified, as well as family and child characteristics that predict high level aggression trajectories. THREE TRAJECTORIES OF PHYSICAL AGGRESSION WERE IDENTIFIED: 1. children (28% of sample) who displayed little or no physical aggression, 2. approximately 58% followed a rising trajectory of modest aggression, and 3. a rising trajectory of high physical aggression (14%). Children who are at highest risk of not learning to regulate physical aggression in early childhood have mothers with a history of antisocial behaviour during their school years, mothers who start childbearing early and who smoke during pregnancy, and parents who have low income and have serious problems living together. Preventive interventions should target families with high-risk profiles on these variables.


Asymmetric effects of fine particulate matter and stringency policy on COVID-19 intensity.
This study aims to examine the influence of environmental performance (PM2.5) on COVID-19 intensity . For this purpose, we employ the newly introduced Hidden Panel Cointegration test and Nonlinear Panel Autoregressive Distributed Lag model. Results indicate the asymmetric linkages between PM2.5 and COVID-19 intensity, as the positive shock in PM2.5 raises the COVID-19 intensity by 21%, whereas the negative shock in PM2.5 decreases COVID-19 intensity by 12% in long-run. On the contrary, the positive shock in stringency measures decreases COVID-19 intensity by 42.8%, while the negative shock in stringency policy increases COVID-19 intensity by 66.7%. These findings imply that higher pollution increases the COVID-19 severity while higher stringency measures slow down people's movement and reduce COVID-19 intensity. However, a sudden negative shock in lockdown increases people's interaction, leading to a higher spread of the virus. These results suggest that governments should adopt stringent action plans to contain the transmissibility of COVID-19.


HDAC4 controls histone methylation in response to elevated cardiac load.
In patients with heart failure, reactivation of a fetal gene program, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), is a hallmark for maladaptive remodeling of the LV. The mechanisms that regulate this reactivation are incompletely understood. Histone acetylation and methylation affect the conformation of chromatin, which in turn governs the accessibility of DNA for transcription factors. Using human LV myocardium, we found that, despite nuclear export of histone deacetylase 4 (HDAC4), upregulation of ANP and BNP in failing hearts did not require increased histone acetylation in the promoter regions of these genes. In contrast, di- and trimethylation of lysine 9 of histone 3 (H3K9) and binding of heterochromatin protein 1 (HP1) in the promoter regions of these genes were substantially reduced. In isolated working murine hearts, an acute increase of cardiac preload induced HDAC4 nuclear export, H3K9 demethylation, HP1 dissociation from the promoter region, and activation of the ANP gene. These processes were reversed in hearts with myocyte-specific deletion of Hdac4. We conclude that HDAC4 plays a central role for rapid modifications of histone methylation in response to variations in cardiac load and may represent a target for pharmacological interventions to prevent maladaptive remodeling in patients with heart failure.


Similar patterns of mitochondrial vulnerability and rescue induced by genetic modification of alpha-synuclein, parkin, and DJ-1 in Caenorhabditis elegans.
How genetic and environmental factors interact in Parkinson disease is poorly understood. We have now compared the patterns of vulnerability and rescue of Caenorhabditis elegans with genetic modifications of three different genetic factors implicated in Parkinson disease (PD). We observed that expressing alpha-synuclein, deleting parkin (K08E3.7), or knocking down DJ-1 (B0432.2) or parkin produces similar patterns of pharmacological vulnerability and rescue. C. elegans lines with these genetic changes were more vulnerable than nontransgenic nematodes to mitochondrial complex I inhibitors, including rotenone, fenperoximate, pyridaben, or stigmatellin. In contrast, the genetic manipulations did not increase sensitivity to paraquat, sodium azide, divalent metal ions (Fe(II) or Cu(II)), or etoposide compared with the nontransgenic nematodes. Each of the PD-related lines was also partially rescued by the antioxidant probucol, the mitochondrial complex II activator, D-beta-hydroxybutyrate, or the anti-apoptotic bile acid tauroursodeoxycholic acid. Complete protection in all lines was achieved by combining d-beta-hydroxybutyrate with tauroursodeoxycholic acid but not with probucol. These results show that diverse PD-related genetic modifications disrupt the mitochondrial function in C. elegans, and they raise the possibility that mitochondrial disruption is a pathway shared in common by many types of familial PD.


The Lost Crown: A Case of an Aspirated Tooth Crown Causing Post-Obstructive Pneumonia.
Non-asphyxiating foreign body aspiration (FBA) is an uncommon occurrence in adults, but it can lead to serious complications and sequelae. Diagnosis of FBA can be difficult as symptoms can mimic other respiratory diseases and the majority of foreign bodies are not visible on chest X-ray. We report a case of an older male who presented with respiratory failure secondary to pneumonia after aspiration of a dental crown. The patient improved after antibiotic therapy and removal of the foreign body by bronchoscopy. Our case is unusual because the diagnosis was delayed after the aspiration event because the patient was asymptomatic before presenting with pneumonia two years later. This case emphasizes the importance of early recognition and management of possible aspiration events to prevent life-threatening sequelae.


Advising vaccinations for the elderly: a cross-sectional survey on differences between general practitioners and physician assistants in Germany.
In Germany, the coverage of officially recommended vaccinations for the elderly is below a desirable level. It is known that advice provided by General Practitioners and Physician Assistants influences the uptake in patients ≥60 years. Therefore, the predictors of advice-giving behavior by these professions should be investigated to develop recommendations for possible actions for improvement. We conducted a postal cross-sectional survey on knowledge, attitudes and advice - giving behavior regarding vaccinations in the elderly among General Practitioners and Physician Assistants in 4995 practices in Germany. To find specific predictors, we performed logistic regressions with non-advising on any officially recommended vaccination or on three specific vaccinations as four separate outcomes, first using all participants, then only General Practitioners and lastly only Physician Assistants as our study population. Participants consisted of 774 General Practitioners and 563 Physician Assistants, of whom overall 21 % stated to have not advised an officially recommended vaccination in elderly patients. The most frequent explanation was having forgotten about it. The habit of not counselling on vaccinations at regular intervals was associated with not advising any vaccination (OR: 2.8), influenza vaccination (OR: 2.3), and pneumococcal vaccination (OR: 3.1). While more General Practitioners than Physician Assistants felt sufficiently informed (90 % vs. 79 %, p < 0.001), General Practitioners displayed higher odds to not advise specific vaccinations (ORs: 1.8-2.8). To reduce the high risk of forgetting to advice on vaccinations, we recommend improving and promoting standing recall-systems, encouraging General Practitioners and Physician Assistants to counsel routinely at regular intervals regarding vaccinations, and providing Physician Assistants with better, tailor-made information on official recommendations and their changes.


Oral manifestations of acute promyelocytic leukemia.
A study was conducted of 16 patients with acute promyelocytic leukemia. The most common oral manifestations were hemorrhagic diathesis and leukemic involvement. There was gingival bleeding, petechiae, and ecchymosis of the oral mucosa, massive infiltration-induced gingival swelling, ulcerative glossitis, swelling of the tonsils, and facial palsy. Inflammatory stomatitis also occurred. Patients with acute promyelocytic leukemia had a higher incidence and severity of oral bleeding than those with other types of acute leukemia. However, the oral findings in our series were not necessarily specific for acute promyelocytic leukemia because the same oral symptoms occur in other forms of acute leukemia.


Arterial Switch Operation With Neoaortic Valve Replacement in a 13-Year Old Patient With Transposition of Great Arteries With Ventricular Septal Defect and Left Ventricular Outflow Tract Obstruction-A Case Report.
The surgical management of d-transposition of great arteries (d-TGAs) with ventricular septal defect (VSD) and left ventricular outflow tract obstruction (LVOTO) is ever evolving and still remains a challenge because of wide anatomic variability, age of presentation, surgical options available, and their variable long-term results in different series. We describe a patient with d-TGA, VSD, and LVOTO who presented to us at 13 years of age and underwent an arterial switch operation along with neoaortic valve replacement with a mechanical prosthesis. The postoperative course was uneventful, and at hospital discharge, the echocardiogram was satisfactory. We present the pros and cons of this hitherto undescribed treatment option.


Evaluation of six decontamination procedures for isolation of Mycobacterium avium complex from avian feces.
Culture is considered the gold standard for definitive diagnosis of mycobacterial infections. However, consensus about the most suitable culture procedure for isolation of nontuberculous mycobacteria is lacking. The study compared the recoveries of mycobacteria after decontamination of spiked and fresh avian feces with 4% sodium hydroxide (NaOH), 12% sulfuric acid (H2SO4), or 1% cetylperidinium chloride (CPC), with and without mixture of three antibiotics, namely vancomycin (VAN, 100 μg/ml), nalidixic acid (NAL, 100 μg/ml), and amphotericin B (AMB, 100 μg/ml). The antibiotic mixture was referred to as VNA. Decontamination procedures were evaluated using two (n = 2) avian fecal samples spiked with 106, 104, and 102 CFU/ml of Mycobacterium avium subsp. avium (ATCC 15769) and fresh avian feces (n = 42). M. avium subsp. avium was detected on the culture media from spiked samples (106 and 104 CFU/ml) decontaminated with NaOH, NaOH-VNA, H2SO4, and H2SO4 -VNA for 2-6 weeks. These bacteria were detected in 2-4 weeks when using CPC and CPC-VNA. M. avium subsp. avium cannot be isolated on culture media from spiked samples (102 CFU/ml) decontaminated with any decontaminating agent. Two mycobacterial isolates, namely, Mycobacterium terrae and M. engbaekii, were isolated from field samples decontaminated with NaOH and CPC-VNA. With regard to the contamination rate, the use of CPC-VNA showed lower contamination rates (5.5% and 19.0%) from spiked and field samples than those of the other methods (NaOH: 22.2% and 59.5%, NaOH-VNA: 16.7% and 21.4%, H2SO4: 11.1% and 40.5%, H2SO4-VNA: 5.5% and 21.4%, and CPC: 66.7% and 50%). In conclusion, the decontamination of fecal samples following a two-step procedure with 1% CPC and VNA can ensure high recovery rate of many mycobacteria with the lowest contamination in cultures.


Boiling temperature as a scaling parameter for the microscopic relaxation dynamics in molecular liquids.
At sufficiently high temperatures, the center-of-mass microscopic diffusion dynamics of liquids is characterized by a single component, often with weak temperature dependence. In this regime, the effective cage made by the neighbor particles cannot be sustained and readily breaks down, enabling long-range diffusion. As the temperature is decreased, the cage relaxation becomes impeded, leading to a higher viscosity with more pronounced temperature dependence. On the microscopic scale, the sustained caging effect leads to a separation between a faster in-cage relaxation component and a slower cage-breaking relaxation component. The evidence for the separate dynamic components, as opposed to a single stretched component, is provided by quasielastic neutron scattering experiments. We use a simple method to evaluate the extent of the dynamic components separation as a function of temperature in a group of related aromatic molecular liquids. We find that, regardless of the glass-forming capabilities or lack thereof, progressively more pronounced separation between the in-cage and cage-breaking dynamic components develops on cooling down as the ratio of T(b)/T, where T(b) is the boiling temperature, increases. This reflects the microscopic mechanism behind the empirical rule for the glass forming capability based on the ratio of boiling and melting temperatures, T(b)/T(m). When a liquid's T(b)/T(m) happens to be high, the liquid can readily be supercooled below its T(m) because the liquid's microscopic relaxation dynamics is already impeded at T(m), as evidenced by a sustained caging effect manifested through the separation of the in-cage and cage-breaking dynamic components. Our findings suggest certain universality in the temperature dependence of the microscopic diffusion dynamics in molecular liquids, regardless of their glass-forming capabilities. Unless the insufficiently low (with respect to T(b)) melting temperature, T(m), intervenes and makes crystallization thermodynamically favorable when cage-breaking is still unimpeded and the structural relaxation is fast, the liquid is likely to become supercooled. The propensity to supercooling and eventually forming a glass is thus determined by a purely thermodynamic factor, T(b)/T(m).


Magnetic nanoparticles modified with DTPA-AMC-rare earth for fluorescent and magnetic resonance dual mode imaging.
In the present study, we report new water-soluble cell fluorescence imaging and contrast agents that are based on DTPA-AMC(7-amino-4-methyl coumarin)-Eu(3+) and DTPA-AMC(7-amino-4-methyl coumarin)-Gd(3+) compounds conjugated to Fe(3)O(4) NPs via a PEG-NH(2) linker. The novel Fe(3)O(4) NP-conjugates present two main advantages for cell fluorescence labelling: water solubility and targeting ability. The in vitro experiments demonstrate that water-soluble Fe(3)O(4) NPs-DBI-PEG-NH-DTPA-AMC(7-amino-4-methyl coumarin)-Eu(3+) has excellent cell permeating activity. Moreover, the relaxation rate test of Fe(3)O(4) NPs-DBI-PEG-NH-DTPA-AMC(7-amino-4-methyl coumarin)-Gd(3+) shows a higher T1 relaxation effect than traditional DTPA-Gd(3+) MRI agents. According to in vivo liver MRI experiments, better contrast of the liver was achieved after addition of Fe(3)O(4) NPs-DBI-PEG-NH-DTPA-AMC(7-amino-4-methyl coumarin)-Gd(3+). The results will provide a significant guide for researchers exploring the biomedical applications of superparamagnetic Fe(3)O(4) NPs.


The Role of Super-Atom Molecular Orbitals in Doped Fullerenes in a Femtosecond Intense Laser Field.
The interaction of gas phase endohedral fullerene Ho3N@C80 with intense (0.1-5 × 1014 W/cm2), short (30 fs), 800 nm laser pulses was investigated. The power law dependence of Ho3N@C80q+, q = 1-2, was found to be different from that of C60. Time-dependent density functional theory computations revealed different light-induced ionization mechanisms. Unlike in C60, in doped fullerenes, the breaking of the cage spherical symmetry makes super atomic molecular orbital (SAMO) states optically active. Theoretical calculations suggest that the fast ionization of the SAMO states in Ho3N@C80 is responsible for the n = 3 power law for singly charged parent molecules at intensities lower than 1.2 × 1014 W/cm2.


A novel gene encoding amidinotransferase in the cylindrospermopsin producing cyanobacterium Aphanizomenon ovalisporum.
The hepatotoxin cylindrospermopsin is produced by several cyanobacteria species, which may flourish in tropical and sub-tropical lakes. Biosynthesis of cylindrospermopsin is poorly understood but its chemical nature, and feeding experiments with stable isotopes, suggested that guanidinoacetic acid is the starter unit and indicated involvement of a polyketide synthase. We have identified a gene encoding an amidinotransferase from the cylindrospermopsin producing cyanobacterium Aphanizomenon ovalisporum. This is the first report on an amidinotransferase gene in cyanobacteria. It is likely to be involved in the formation of guanidinoacetic acid. The aoaA is located in a genomic region bearing genes encoding a polyketide synthase and a peptide synthetase, further supporting its putative role in cylindrospermopsin biosynthesis.


[Which place for VDD mode single electrode pacemaker?].
VDD mode single electrode pacemaker is a technique of cardiac stimulation which preserves auriculo-ventricular synchronism using a single electrode. Its importance has decreased because of the numerous satisfactions previous by the DDD mode. We describe our experience with this mode and we discuss the advantages, limits and indications of this mode of cardiac stimulation.


Soybean (Glycine max) transformation using immature cotyledon explants.
Agrobacterium tumefaciens-mediated transformation of soybeans can be accomplished using immature zygotic cotyledons as target tissues providing an alternate explant to embryogenic tissue cultures, proliferating meristems, and cotyledonary nodes. The immature cotyledon method includes direct induction of transgenic somatic embryos from the explant plated on selective media after cocultivation, followed by maturation and regeneration of individual somatic embryos into whole plants. Although this method has been improved to be simple, rapid, reproducible, and applicable to a range of cultivars in different maturity groups, the transformation efficiency (Southern-positive, independent plants produced per 100 immature cotyledon explants) is 1.7% and needs to be further increased to make this a robust soybean transformation system. Further refinements of cocultivation conditions, tissue culture, and selection of regenerated transgenic plants will probably result in increases in transformation efficiency.


Health care utilization and cost among children with asthma who were enrolled in a health maintenance organization.
To measure the impact of asthma on the use and cost of health care by children in a managed care organization. Population-based historical cohort study. A medium-sized staff model health maintenance organization in western Washington state. All 71 818 children, between age 1 to 17 years, who were enrolled and used services during 1992. Children were identified with one or more asthma diagnoses during 1992 using automated encounter data. Nonurgent outpatient visits, pharmacy fills, urgent care visits, and hospital days, as well as associated costs were measured. All services were categorized as asthma care or nonasthma care. Multivariate regression analysis was used to compute marginal cost for asthma (difference in total cost between children with asthma and other children using services, adjusted for covariates). Treated prevalence of asthma was 4.9%. Children with asthma incurred 88% more costs ($1060.32 vs $563. 81/yr), filled 2.77 times as many prescriptions (11.59 vs 4.19/yr), made 65% more nonurgent outpatient visits (5.75 vs 3.48/yr), and had twice as many inpatient days (.23 vs .11/yr) compared with the general population of children using services. Asthma care represented 37% of all health care received by children with asthma, while the remaining 63% were for nonasthma services. Almost two-thirds of asthma-related costs were attributable to nonurgent outpatient care and prescriptions; only one third was attributable to urgent care and hospitalizations. Controlling for age, sex, and comorbidities, the marginal cost of asthma was $615.17/yr (95% confidence interval $502.73, $727.61), which includes asthma as well as nonasthma services. This marginal cost represents 58% of all health care costs for children with asthma. Children with asthma use significantly more health services (and incur significantly more costs) than other children using services, attributable largely to asthma care. The majority of all health care costs for children with asthma were for nonasthma services. Urgent care visits and hospitalizations are less important components of asthma costs in this managed care organization than has been found in other national studies.


Revisiting Unplanned Endotracheal Extubation and Disease Severity in Intensive Care Units.
Most reports regarding unplanned extubation (UE) are case-control studies with matching age and disease severity. To avoid diminishing differences in matched factors, this study with only matching duration of mechanical ventilation aimed to re-examine the risk factors and the factors governing outcomes of UE in intensive care units (ICUs). This case-control study was conducted on 1,775 subjects intubated for mechanical ventilation. Thirty-seven (2.1%) subjects with UE were identified, and 156 non-UE subjects were randomly selected as the control group. Demographic data, acute Physiological and Chronic Health Evaluation II (APACHE II) scores, and outcomes of UE were compared between the two groups. Logistic regression analysis was used to identify the risk factors of UE. Milder disease, younger age, and higher Glasgow Coma Scale (GCS) scores with more frequently being physically restrained (all p<0.05) were related to UE. Logistic regression revealed that APACHE II score (odds ratio (OR) 0.91, p<0.01), respiratory infection (OR 0.24, p<0.01), physical restraint (OR 5.36, p<0.001), and certain specific diseases (OR 3.79-5.62, p<0.05) were related to UE. The UE patients had a lower ICU mortality rate (p<0.01) and a trend of lower in-hospital mortality rate (p = 0.08). Cox regression analysis revealed that in-hospital mortality was associated with APACHE II score, age, shock, and oxygen used, all of which were co-linear, but not UE. The results showed that milder disease with higher GCS scores thereby requiring a higher use of physical restraints were related to UE. Disease severity but not UE was associated with in-hospital mortality.


Plasma Lp(a) levels correlate with number, severity, and length-extension of coronary lesions in male patients undergoing coronary arteriography for clinically suspected coronary atherosclerosis.
The relation between lipoprotein(a) [Lp(a)] as an independent risk factor for coronary atherosclerosis and the severity and extension of angiographically detectable coronary atherosclerotic lesions has not been systematically evaluated. In 118 male patients (54.3 +/- 7.4 years) with suspected coronary artery disease and without a history of myocardial infarction undergoing coronary angiography, the relation between plasma Lp(a) levels and other lipoproteins and the severity and extension of coronary lesions was studied. The coronary angiograms were evaluated in a blinded manner according to three scores: vessel score (0 to 3 points for 0 to 3 vessels with stenoses > or = 70%), stenosis score (0 to 32 points; number and severity of coronary stenoses or lesions), and extent score (0 to 100 points; length-extension of all coronary lesions in relation to the total coronary vessel length). The score values obtained were analyzed for correlations with age and levels of total cholesterol (6.08 +/- 1.26 mmol/L; mean +/- SD), high-density lipoprotein cholesterol (1.04 +/- 0.33 mmol/L), low-density lipoprotein cholesterol (4.18 +/- 1.15 mmol/L), triglycerides (1.88 +/- 1.37 mmol/L), and Lp(a) in plasma (19.5 +/- 22.6 mg/dL). Bivariate correlation analysis resulted in positive correlations between Lp(a) and vessel score (P < .01), stenosis score (P < .01), and extent score (P < .05). With multivariate analyses, besides Lp(a) plasma level (nl), only patient age showed a significant correlation to all three scores used, whereas none of the lipid parameters correlated significantly with all three scores.


Vestibular syndrome: a change in internal spatial representation.
The vestibular system contributes to a wide range of functions from reflexes to spatial representation. This paper reviews behavioral, perceptive, and cognitive data that highlight the role of changes in internal spatial representation on the vestibular syndrome. Firstly, we review how visual vertical perception and postural orientation depend on multiple reference frames and multisensory integration and how reference frames are selected according to the status of the peripheral vestibular system (i.e., unilateral or bilateral hyporeflexia), the environmental constraints (i.e., sensory cues), and the postural constraints (i.e., balance control). We show how changes in reference frames are able to modify vestibular lesion-induced postural and locomotor deficits and propose that fast changes in reference frame may be considered as fast-adaptive processes after vestibular loss. Secondly, we review data dealing with the influence of vestibular loss on higher levels of internal representation sustaining spatial orientation and navigation. Particular emphasis is placed on spatial performance according to task complexity (i.e., the required level of spatial knowledge) and to the sensory cues available to define the position and orientation within the environment (i.e., real navigation in darkness or visual virtual navigation without any actual self-motion). We suggest that vestibular signals are necessary for other sensory cues to be properly integrated and that vestibular cues are involved in extrapersonal space representation. In this respect, vestibular-induced changes would be based on a dynamic mental representation of space that is continuously updated and that supports fast-adaptive processes.


[Clinical study on chitosan in prevention of knee adhesion after patellar operation].
To investigate the clinical effect of chitosan in prevention of knee dysfunction due to adhesion after operation for patellar fracture. From March to October 1999, 40 cases of patellar fracture were treated by internal fixation, with intra-articular injection of 2% chitosan in only 24 cases after fixation and with no chitosan injection in 16 cases (control group). The function of the knee joint, including extension and flexion, was evaluated 1 month and 1 year after operation respectively. One month after operation, the knees with chitosan injection could actively move in the average range of 104 degrees +/- 23 degrees, and the knees in the control group could move in the average range of 72 degrees +/- 16 degrees, which showed significant difference between two groups (P < 0.01); 1 year after operation, the range of movement of the knees with injection was 165 degrees +/- 38 degrees on average, and that of the knees in the control group was 110 degrees +/- 31 degrees, which also indicated significant difference between two groups (P < 0.05). Medical chitosan could effectively prevent or reduce the post-operative adhesion of knee joint after patellar operation.


Parallel analysis of ribonucleotide-dependent deletions produced by yeast Top1 in vitro and in vivo.
Ribonucleotides are the most abundant non-canonical component of yeast genomic DNA and their persistence is associated with a distinctive mutation signature characterized by deletion of a single repeat unit from a short tandem repeat. These deletion events are dependent on DNA topoisomerase I (Top1) and are initiated by Top1 incision at the relevant ribonucleotide 3'-phosphodiester. A requirement for the re-ligation activity of Top1 led us to propose a sequential cleavage model for Top1-dependent mutagenesis at ribonucleotides. Here, we test key features of this model via parallel in vitro and in vivo analyses. We find that the distance between two Top1 cleavage sites determines the deletion size and that this distance is inversely related to the deletion frequency. Following the creation of a gap by two Top1 cleavage events, the tandem repeat provides complementarity that promotes realignment to a nick and subsequent Top1-mediated ligation. Complementarity downstream of the gap promotes deletion formation more effectively than does complementarity upstream of the gap, consistent with constraints to realignment of the strand to which Top1 is covalently bound. Our data fortify sequential Top1 cleavage as the mechanism for ribonucleotide-dependent deletions and provide new insight into the component steps of this process.


A comparison of two tuberculins in nonsensitized macaques.
Two tuberculins (mammalian and Old Tuberculin) were compared in three species of macaques after one of the tuberculins elicited nonspecific reactions up to 72 hours after intradermal inoculation in nontuberculous monkeys. A significant difference in initial intradermal eyelid reactivity between the tuberculins was found in some subjects. The heterogeneity of tuberculins and the necessity of accurate interpretation of intradermal testing are important components in addressing tuberculosis screening in nonhuman primate colonies.


A temporal window for estimating surface brightness in the Craik-O'Brien-Cornsweet effect.
The central edge of an opposing pair of luminance gradients (COC edge) makes adjoining regions with identical luminance appear to be different. This brightness illusion, called the Craik-O'Brien-Cornsweet effect (COCe), can be explained by low-level spatial filtering mechanisms (Dakin and Bex, 2003). Also, the COCe is greatly reduced when the stimulus lacks a frame element surrounding the COC edge (Purves et al., 1999). This indicates that the COCe can be modulated by extra contextual cues that are related to ideas about lighting priors. In this study, we examined whether processing for contextual modulation could be independent of the main COCe processing mediated by the filtering mechanism. We displayed the COC edge and frame element at physically different times. Then, while varying the onset asynchrony between them and changing the luminance contrast of the frame element, we measured the size of the COCe. We found that the COCe was observed in the temporal range of around 600-800 ms centered at the 0 ms (from around -400 to 400 ms in stimulus onset asynchrony), which was much larger than the range of typical visual persistency. More importantly, this temporal range did not change significantly regardless of differences in the luminance contrast of the frame element (5-100%), in the durations of COC edge and/or the frame element (50 or 200 ms), in the display condition (interocular or binocular), and in the type of lines constituting the frame element (solid or illusory lines). Results suggest that the visual system can bind the COC edge and frame element with a temporal window of ~1 s to estimate surface brightness. Information from the basic filtering mechanism and information of contextual cue are separately processed and are linked afterwards.


Effects of varying attentional focus on health-related physical fitness performance.
Assessing health-related physical fitness is important for determining health status. However, verbal instructions provided during an assessment generally do not specify direction of attentional focus. This investigation examined the effect of attentional focus on performance outcomes during appraisals of health-related physical fitness. Eight females (25.0 ± 4.0 years) and 8 males (26.3 ± 3.9 years) completed 7 physical fitness tests of the Canadian Physical Activity, Fitness and Lifestyle Approach (modified Canadian Aerobic Fitness Test, grip strength, push-ups, sit and reach, partial curl-ups, vertical jump, and back extension) on 3 different days, each separated by 1 week. On day 1, no attentional focus was specified. On days 2 and 3, participants were asked to adopt an external focus (instructions focused attention away from the body) or an internal focus (instructions focused attention on the body's movement) in randomized order. Irrespective of sex, adopting an external focus resulted in significantly better performance on all tests when compared with no focus or internal-focus conditions. An internal focus also resulted in performance decrements for grip strength, push-ups, and vertical jump vs. no focus. These results demonstrate that instructing individuals to adopt an external focus provides a performance advantage on appraisals of aerobic and musculoskeletal fitness, whereas an internal focus may hinder performance. In some participants, these scores may convert to a rating of health status that is 1 health benefit zone higher or lower, respectively. This highlights further the importance of formulating verbal instructions that incorporate attentional focus for optimal performance on appraisals of physical fitness.


Initial Assessment and Management of Select Musculoskeletal Injuries: A Team Physician Consensus Statement.
Musculoskeletal injuries occur frequently in sport during practice, training and competition. Injury assessment and management are common responsibilities for the team physician. Initial Assessment and Management of Musculoskeletal Injury - A Team Physician Consensus Statement is title 23 in a series of annual consensus documents written for the practicing team physician. This statement was developed by the Team Physician Consensus Conference (TPCC), an annual project-based alliance of six major professional associations. The goal of this document is to help the team physician improve the care and treatment of the athlete by understanding the initial assessment and management of selected musculoskeletal injuries.


Postnatal management of fetal and neonatal alloimmune thrombocytopenia: the role of matched platelet transfusion and IVIG.
We evaluated the effects of platelet transfusions and intravenous immunoglobulin (IVIG) in neonates with fetal and neonatal alloimmune thrombocytopenia (FNAIT) with and without antenatal treatment with IVIG. Records of neonates with FNAIT admitted between January 2000 and November 2005 were reviewed. The patients were divided into group I, treated antenatally with IVIG for known FNAIT, and group II, postnatally diagnosed with FNAIT. The primary outcome was the time interval to reach a platelet level above 100 x 10(9)/L in relation to the type of treatment. Nineteen neonates with FNAIT were identified, 13 in group I and 6 in group II. In group I, four children were born with a platelet count above 100 x 10(9)/L and never needed treatment, and four received a single matched platelet transfusion at birth with a maintained response. Five neonates received IVIG and one matched transfusion, with all but one rapidly responding. In antenatally treated cases, postnatal IVIG had no apparent effect on the platelet count. In group II, two neonates died on day 1 with severe intracranial hemorrhage. Two of the four other patients responded to a number of unmatched platelet transfusions, with one neonate rapidly responding after one matched transfusion, while another needed nine matched transfusions before a persistent adequate platelet count was reached after 9 weeks. Postnatal IVIG had no apparent effect on the platelet count in any of our cases. In neonates with FNAIT treated antenatally with IVIG, neonatal management using a single matched platelet transfusion was adequate in all cases. In neonatally diagnosed cases not treated before birth, multiple matched platelet transfusions may be required. We found no evidence to support the use of IVIG in neonates with FNAIT.


A point mutation in the env gene of a murine leukemia virus induces syncytium formation and neurologic disease.
TR1.3 is a Friend-related murine leukemia virus that has been shown to cause intracerebral hemorrhages and neurologic disease due to infection and subsequent cytopathology of cerebral vessel endothelium. A striking feature of this pathology is the formation of endothelial cell syncytia. The pathogenesis of this disease has now been mapped to a single amino acid substitution of tryptophan to glycine in the variable region of the envelope protein. This same mutation enabled TR1.3 to form syncytia and retard cell proliferation in vitro in the SC-1 mouse embryoblast line but did not affect the pH dependence of viral entry. These results demonstrate that subtle molecular changes in retroviral env genes can induce both syncytium formation and overt clinical disease.


Intrinsic and antigen-induced airway hyperresponsiveness are the result of diverse physiological mechanisms.
Airway hyperresponsiveness (AHR) is a defining feature of asthma. We have previously shown, in mice sensitized and challenged with antigen, that AHR is attributable to normal airway smooth muscle contraction with exaggerated airway closure. In the present study we sought to determine if the same was true for mice known to have intrinsic AHR, the genetic strain of mice, A/J. We found that A/J mice have AHR characterized by minimal increase in elastance following aerosolized methacholine challenge compared with mice (BALB/c) that have been antigen sensitized and challenged [concentration that evokes 50% change in elastance (PC(50)): 22.9 +/- 5.7 mg/ml for A/J vs. 3.3 +/- 0.4 mg/ml for antigen-challenged and -sensitized mice; P < 0.004]. Similar results were found when intravenous methacholine was used (PC(30) 0.22 +/- 0.08 mg/ml for A/J vs. 0.03 +/- 0.004 mg/ml for antigen-challenged and -sensitized mice). Computational model analysis revealed that the AHR in A/J mice is dominated by exaggerated airway smooth muscle contraction and that when the route of methacholine administration was changed to intravenous, central airway constriction dominates. Absorption atelectasis was used to provide evidence of the lack of airway closure in A/J mice. Bronchoconstriction during ventilation with 100% oxygen resulted in a mean 9.8% loss of visible lung area in A/J mice compared with 28% in antigen-sensitized and -challenged mice (P < 0.02). We conclude that the physiology of AHR depends on the mouse model used and the route of bronchial agonist administration.


Supported Ultra-Thin Alumina Membranes with Graphene as Efficient Interference Enhanced Raman Scattering Platforms for Sensing.
The detection of Raman signals from diluted molecules or biomaterials in complex media is still a challenge. Besides the widely studied Raman enhancement by nanoparticle plasmons, interference mechanisms provide an interesting option. A novel approach for amplification platforms based on supported thin alumina membranes was designed and fabricated to optimize the interference processes. The dielectric layer is the extremely thin alumina membrane itself and, its metallic aluminum support, the reflecting medium. A CVD (chemical vapor deposition) single-layer graphene is transferred on the membrane to serve as substrate to deposit the analyte. Experimental results and simulations of the interference processes were employed to determine the relevant parameters of the structure to optimize the Raman enhancement factor (E.F.). Highly homogeneous E.F. over the platform surface are obtained, typically 370 ± (5%), for membranes with ~100 nm pore depth, ~18 nm pore diameter and the complete elimination of the Al2O3 bottom barrier layer. The combined surface enhanced Raman scattering (SERS) and interference amplification is also demonstrated by depositing ultra-small silver nanoparticles. This new approach to amplify the Raman signal of analytes is easily obtained, low-cost and robust with useful enhancement factors (~400) and allows only interference or combined enhancement mechanisms, depending on the analyte requirements.