Induction of apoptosis and cell cycle arrest by NS398 in oral squamous cell carcinoma cells via downregulation of E2 promoter-binding factor-1.
Overexpression of cyclooxygenase-2 (COX-2) plays an important role in development and progression of different human cancers, but the underlying molecular mechanisms remain to be defined. Tissue specimens of normal oral epithelia (n=9), dysplasia (n=38), and oral squamous cell carcinoma (SCC, n=54) were immunohistochemically analyzed for COX-2 and E2F-1 expression. A human oral SCC cell line, Tca8113, was used to assess NS398 antitumor activity. PGE2 levels were measured by using radioimmunoassay, and COX-2, pRb, and E2F-1 proteins were determined by Western blot assay. We found expression of COX-2 and E2F-1 proteins was significantly increased in both oral dysplasia and SCC compared to the normal epithelium. Increased COX-2 expression was associated with E2F-1 expression in both oral dysplasia and SCC. NS398 treatment reduced viability of Tca8113 cells in a dose- and time-dependent manner. NS398 suppressed PGE2 levels, a product of COX-2 enzyme, in the tumor cells. The reduced cell viability is due to induction of apoptosis by NS398, which activates caspase-3, but does not inhibit bcl-2. NS398 also induced tumor cell arrest at G1 phase of the cell cycle and inhibited expression of COX-2, pRb and E2F-1 proteins. This study provides evidence that E2F-1 and COX-2 are overexpressed in oral cancer, and further supports suppression of COX-2 in control of oral cancer.


Metabolism of Oat Leaves during Senescence : VII. The Interaction of Carbon Dioxide and Other Atmospheric Gases with Light in Controlling Chlorophyll Loss and Senescence.
In air largely freed from CO(2), senescence of isolated oat (Avena sativa cv Victory) seedling leaves is no longer prevented by white light; instead, the leaves lose both chlorophyll and protein as rapidly as in the dark. Senescence in light is also accelerated in pure O(2), but it is greatly delayed in N(2); 100% N(2) preserves both protein and chlorophyll in light and in darkness. In light in air, most of the compounds tested that had previously been found to delay or inhibit senescence in darkness actually promote the loss of chlorophyll, but they do not promote proteolysis. Under these conditions, proteolysis can therefore be separated from chlorophyll loss. But in light minus CO(2), where chlorophyll loss is rapid in controls, two of these same reagents prevent the chlorophyll loss. Unlike the many reagents whose action in light is thus the opposite of that in darkness, abscisic acid, which promotes chlorophyll loss in the dark, also promotes it in light with or without CO(2). Kinetin, which prevents chlorophyll loss in the dark, also prevents it in light minus CO(2). In general, therefore, the responses to light minus CO(2) are similar to the responses to darkness, and (with the exception of abscisic acid and kinetin) opposite to the response to light in air.


Allonursing in Wild and Farm Animals: Biological and Physiological Foundations and Explanatory Hypotheses.
The dams of gregarious animals must develop a close bond with their newborns to provide them with maternal care, including protection against predators, immunological transference, and nutrition. Even though lactation demands high energy expenditures, behaviors known as allonursing (the nursing of non-descendant infants) and allosuckling (suckling from any female other than the mother) have been reported in various species of wild or domestic, and terrestrial or aquatic animals. These behaviors seem to be elements of a multifactorial strategy, since reports suggest that they depend on the following: species, living conditions, social stability, and kinship relations, among other group factors. Despite their potential benefits, allonursing and allosuckling can place the health and welfare of both non-filial dams and alien offspring at risk, as it augments the probability of pathogen transmission. This review aims to analyze the biological and physiological foundations and bioenergetic costs of these behaviors, analyzing the individual and collective advantages and disadvantages for the dams' own offspring(s) and alien neonate(s). We also include information on the animal species in which these behaviors occur and their implications on animal welfare.


Orthodontic bracket bonding without previous adhesive priming: A meta-regression analysis.
To determine the consensus among studies that adhesive resin application improves the bond strength of orthodontic brackets and the association of methodological variables on the influence of bond strength outcome. In vitro studies were selected to answer whether adhesive resin application increases the immediate shear bond strength of metal orthodontic brackets bonded with a photo-cured orthodontic adhesive. Studies included were those comparing a group having adhesive resin to a group without adhesive resin with the primary outcome measurement shear bond strength in MPa. A systematic electronic search was performed in PubMed and Scopus databases. Nine studies were included in the analysis. Based on the pooled data and due to a high heterogeneity among studies (I(2) = 93.3), a meta-regression analysis was conducted. The analysis demonstrated that five experimental conditions explained 86.1% of heterogeneity and four of them had significantly affected in vitro shear bond testing. The shear bond strength of metal brackets was not significantly affected when bonded with adhesive resin, when compared to those without adhesive resin. The adhesive resin application can be set aside during metal bracket bonding to enamel regardless of the type of orthodontic adhesive used.


Marginal bone loss at implants with different surface characteristics - A 20-year follow-up of a randomized controlled clinical trial.
This report is a 20-year follow-up of a randomized controlled clinical trial evaluating the potential long-term effect of a modified implant surface on the preservation of the peri-implant marginal bone level. In each of 51 patients and for each fixed partial denture (FPD), by randomization at least one implant installed had a non-modified turned surface and one a modified and roughened surface (TiOblast® ). Clinical and radiological examinations were performed at various follow-up intervals. Primary outcome variables were peri-implant marginal bone level change from time of loading and proportion of implants with no bone loss at 20 years. Multilevel analysis followed by nonparametric and Pearson's Chi-Square tests were applied for statistical analysis. At the 20-year follow-up, 25 patients carrying 64 implants were available for evaluation. Turned and TiOblast implants presented with a mean bone level change from the time of FDP delivery amounting to -0.41 mm (95% CI -0.84/0.02) and -0.83 mm (95% CI -1.38/-0.28) respectively (inter-group comparison p > .05). 47% of the Turned and 34% TiOblast implants (p > .05) showed no bone loss. All but one of these implants were free of bacterial plaque and inflammation as well as presented with probing pocket depths ≤5 mm at both the 5- and 20-year follow-up examinations. It is suggested that a moderate increase of implant surface roughness has no beneficial effect on long-term preservation of the peri-implant marginal bone level.


Exposed inferior alveolar neurovascular bundle during surgical removal of a residual cyst.
Iatrogenic neurodeficiency is one of the most distressing complications to any surgical procedure. The prediction of close proximity of the oral lesions to the inferior alveolar neurovascular bundle is extremely important. Furthermore, iatrogenic neurosensory dysfunctions of the facial region involve important medicolegal issues. In this report, we describe the case of a patient who did not show either paresthesia or anesthesia after the surgical removal of a mandibular residual cyst that exhibited adherence to the inferior alveolar nerve bundle.


The Contested Whiteness of Arab Identity in the United States: Implications for Health Disparities Research.
In response to the Institute on Minority Health and Health Disparities' (NIMHD) new health disparities research framework, we call on the National Institutes of Health (NIH) to acknowledge Arabs in the United States as a health disparity population. Arab classification as White leads to their cultural invisibility and perpetuates a cycle of undocumented health disparities.We provide examples of how this contested identity reinforces challenges associated with identifying this population and contributes to enactments of structural violence and undocumented health disparities. Decades of research with Arabs in the United States provides consistent evidence that their health does not fit the health profile of White Americans and that Arabs do not benefit from Whiteness and White privilege associated with their White racial categorization. On the contrary, Arabs in the United States experience discrimination and health disparities that require urgent attention; this can be achieved only by identifying the population with a racial category other than White.We conclude with recommendations to NIH and NIMHD to revise their definition of health disparity populations to include Arabs in the United States.


Features and treatment of rabies.
The epidemiology, virology, transmission, pathology, clinical manifestations, diagnosis, and treatment of rabies infection are described. The incidence of rabies is increasing. The virus is usually transmitted through the bite of an infected animal; however, corneal transplantation from an infected donor and viral inhalation may also result in infection. The clinical course of rabies occurs in five stages. Stage I is the incubation period, stage II is the prodromal period, stage III is the neurological period, stage IV is coma, and stage V, which occurs infrequently, is recovery. Early in the disease, constitutional symptoms and signs of local wound healing may be present. During the later stages, a wide array of clinical manifestations may occur, including hydrophobia and aerophobia, which are pathognomonic for rabies. Once inoculation with the rabies virus is suspected, prompt therapy, including appropriate wound care and rabies vaccination, is imperative, even in previously immunized individuals. Human diploid-cell vaccine and rabies vaccine adsorbed, which stimulate the production of antibodies, and human rabies immune globulin, which provides protective antibodies, are nearly 100% effective in preventing progression from stage I disease. If left untreated, rabies is usually fatal. However, treatment with human diploid-cell vaccine or rabies vaccine adsorbed and with human rabies immune globulin is nearly always curative if initiated early in the incubation period.


Shape of the liquid-vapor coexistence curve for temperature and density dependent effective interactions.
The asymmetry of the coexistence curve that is observed in several micellar systems is discussed in relation with the dependence of the effective interaction on temperature and density. Standard results for the diameter of the coexistence curve in the van der Waals theory are generalized so as to deal with this combined dependence. The qualitative trends so deduced are assessed by comparison with coexistence curves of Yukawa fluids computed with integral equation theories. The role of the variables used to plot the coexistence curve and the nonlinear behavior of its diameter beyond the critical region are discussed in relation with the decrease of the interaction strength with density. The possibility of using the asymmetry of the coexistence curve as an indicator of the state dependence of the effective interaction is finally discussed.


Pilot study on the effect of subcutaneous administration of lactated Ringer's solution on biochemistry parameters in healthy euvolemic cats.
Subcutaneous fluid administration is a commonly used therapy in veterinary practice. Its safety and efficacy have been demonstrated in human clinical studies, but have only rarely been discussed in the veterinary literature. This prospective observational study was performed to evaluate changes during a 24 h period in serum biochemistries associated with administration of lactated Ringer's solution subcutaneously to healthy cats. Lactated Ringer's solution was administered subcutaneously once to ten healthy, euvolemic cats at a dose of 22 mL kg-1. Blood biochemistry analytes were sampled at baseline and at serial time points for a total of 24 h. Changes in biochemical analytes at each time point were compared to baseline and evaluated for statistical significance. Serum blood urea nitrogen (BUN) was significantly less than baseline at 4, 6, 12, 18, and 24 h post-infusion. Serum creatinine was significantly less than baseline at 2, 4 and 6 h. Packed cell volume (PCV) was significantly less than baseline at 6, 12, 18, and 24 h. Total plasma proteins were significantly less than baseline at all time points. Serum electrolytes did not change from baseline at any time point. Urine specific gravity was significantly increased from baseline only at 6 h post-Lactated Ringer's solution (LRS) administration. Subcutaneous administration of lactated Ringer's solution appears to result in haemodilution with minimal change to serum electrolyte concentrations in clinically normal, euvolemic cats.


Predictors of clinical response to interleukin-2--based immunotherapy in melanoma patients: a French multiinstitutional study.
Various parameters have been reported to be correlated with response to interleukin-2 (IL-2) therapy. A multiinstitutional study was performed to assess by multivariate analysis the predictive value of known clinical and biologic melanoma prognostic markers recorded before the onset of IL-2 therapy on the likelihood of objective clinical response. Serum C-reactive protein (CRP), IL-6, and lactate dehydrogenase (LDH) levels were measured in 81 metastatic melanoma patients included in different IL-2-based regimens before the starting of IL-2-therapy. Clinically defined prognostic groups, i.e., patients with superficial or visceral metastases, were also analyzed for response correlates. Patients were evaluated for response to treatment 4 to 6 weeks after completion of one course of therapy. On univariate analysis, the pretreatment values of CRP (P = .001), IL-6 (P = .007), and LDH (P = .02) and site of metastases (P = .0004) were correlated with clinical response. However, only CRP (P < .007) and clinically defined group (P < .004) were independent predictors on multifactorial analysis. Indeed, when adjusted to CRP, IL-6 tended to improve patient selection, but did not reach statistical significance (P = .07). Furthermore, using multivariate survival analysis based on the Cox proportional hazards model, only CRP was found to be an independent prognostic factor for survival (P < .0001). In this study, patients with high serum levels of CRP and/or visceral organ involvement before therapy were unlikely to respond to IL-2 therapy. Therefore, clinical classification based on the site of metastases and serum CRP determination before the start of IL-2 therapy may help to improve selection of melanoma patients who may benefit from IL-2 and could prevent unnecessary morbidity.


Lung inflammation and epithelial changes in a murine model of atopic asthma.
A murine model of allergen-induced airway inflammation and epithelial phenotypic change, and the time-courses of these events, are described. Mice were sensitized to ovalbumin using an adjuvant-free protocol, and challenged by multiple intratracheal instillations of ovalbumin by a non-surgical technique. Many of the characteristic features of human atopic asthma were seen in the mice. A marked eosinophilic infiltration of lung tissue and airways followed allergen challenge, and its severity increased with each challenge, as did the number of eosinophils in the blood. Lymphocytes, neutrophils, and monocytes also invaded the lungs. Airway macrophages showed signs of activation, their appearance resembling those recovered from antigen-challenged human asthmatic airways. The airway epithelium was thickened and displayed a marked goblet cell hyperplasia in terminal bronchioles and larger airways. After repeated challenges, the reticular layer beneath the basement membrane of the airway epithelium showed fibrosis, reproducing a commonly observed histologic feature of human asthma. Goblet cell hyperplasia began to appear before eosinophils or lymphocytes had migrated across the airway epithelium, and persisted for at least 11 days after the third intratracheal challenge with ovalbumin, despite the number of inflammatory cells in the lungs and airways having decreased to near-normal levels by 4 days. Plugs of mucus occluded some of the airways. These results indicate that some of the phenotypic changes in airway epithelium that follow an allergic response in the lung can be initiated before the migration of eosinophils or lymphocytes across the epithelial layer.


Apraxia.
In this review, we present a summary of some of the most pertinent new research on aspects of apraxia. Rather than attempt a review of all neurologic syndromes that have been identified as forms of apraxia, such as buccofacial, truncal, apraxia of eye opening, and apraxia of speech, we focus on current literature and trends in the study of limb apraxia. Although the classic empirical approach to the study of apraxia has been through systematic neuropsychologic assessment of various aspects of the syndrome, questions remain regarding the exact neural substrate that forms the foundation of the praxis system. More recent work using sophisticated neuroimaging methods has yielded a wealth of new data that contributes significantly to our understanding of the neuroanatomic correlates of this complex disorder. In addition, the results of recent sophisticated neuropsychologic studies have suggested modifications to classic cognitive models of apraxia. A discussion of current work and directions for future research are also provided.


Auto fluorescence of intervertebral disc tissue: a new diagnostic tool.
The paper reports on auto fluorescence phenomena of inter-vertebral human discs. It systematically investigates the auto fluorescence effects of ex vivo disc specimen and reports on surgical cases to demonstrate the potential value of the new method. The paper offers biologic explanations of the phenomenon and discusses the potential value of the UV auto fluorescence technique as a diagnostic tool. Intra- and postoperative observations are made by a surgical microscope with an integrated UV light source. Quantitative measurements were carried out using a photon counter and a spectrometer ex vivo. The auto fluorescence phenomenon allows the differentiation of traumatized and degenerated disc tissue intraoperatively in some cases, it allows the differentiation of bony and collagen endplate in cervical disc surgery. The source of the auto fluorescent light emission are amino acids of the collagen molecules. The proteoglycan components and the liquid components of the disc do not show relevant auto fluorescence. Emission wavelength of disc material is equivalent to color perception. It differs due to different collagen composition of the intervertebral disc components from yellow-green to blue-green and can be visualized in situ by naked eye.UV-auto fluorescence of inter-vertebral discs is a new clinical tool that has the potential to differentiate disc material from the anatomical surrounding, to distinguish between different fractions of the disc and to give information on the quality and status of the disc material. Since the technology has just emerged, it needs further investigations to quantify the clinical observations reported in this paper.


Accuracy of Point-of-Care-Ultrasonography in Confirming Shoulder Reduction in Emergency Departments.
Aims Accurate identification of the successful reduction of a dislocated shoulder could avoid additional episodes of procedural sedation and repeated performance of X-rays. The objective of this study was to assess the diagnostic accuracy of point-of-care-ultrasound (POCUS) in the confirmation of a successful joint reduction in patients with shoulder dislocation. Methods This was a single-centre, prospective observational study set in an urban academic ED in Ireland, with a convenience sample of adult patients with shoulder dislocation on X-ray. Ultrasound was performed on participants before and after joint reduction using a posterior approach technique. The operator's confidence levels were recorded after image acquisition. Results Thirty-three subjects were recruited. All dislocations were correctly identified on pre-reduction US, indicating a sensitivity of 100% (CI 89.42 - 100). Post-reduction US confirmed successful reduction in 30 subjects that were subsequently reported as such on X-Ray, giving it a specificity of 100% (CI 88.43 - 100). Failure to achieve reduction was correctly identified on US in three cases, resulting in post-reduction US Sensitivity of 100% (CI 29.24 - 100) and 100% accuracy (CI 89.42 - 100). Conclusion This study has shown that POCUS, with a posterior approach technique, has 100% sensitivity and specificity in confirming successful shoulder reduction in the ED.


Whole-Genome Sequencing and Bioinformatics Analysis of Apiotrichum mycotoxinivorans: Predicting Putative Zearalenone-Degradation Enzymes.
Biological detoxification techniques have been developed by using microorganisms such as bacteria, yeast, and fungi to eliminate mycotoxin contamination. However, due to the lack of molecular details of related enzymes, the underlying mechanism of detoxification of many mycotoxins remain unclear. On the other hand, the next generation sequencing technology provides a large number of genomic data of microorganisms that can degrade mycotoxins, which makes it possible to use bioinformatics technology to study the molecular details of relevant enzymes. In this paper, we report the whole-genome sequencing of Apiotrichum mycotoxinivorans (Trichosporon mycotoxinivorans in old taxonomy) and the putative Baeyer-Villiger monooxygenases (BVMOs) and carboxylester hydrolases for zearalenone (ZEA) degradation through bioinformatic analysis. In particular, we developed a working pipeline for genome-scaled prediction of substrate-specific enzyme (GPSE, available at https://github.com/JinyuanSun/GPSE), which ultimately builds homologous structural and molecular docking models to demonstrate how the relevant degrading enzymes work. We expect that the enzyme-prediction woroflow process GPSE developed in this study might help accelerate the discovery of new detoxification enzymes.


Defining and applying a method for improving the sensitivity and specificity of an emergency department early event detection system.
The sensitivity and specificity of syndrome definitions used in early event detection (EED) systems affect the usefulness of the system for end-users. The ability to calculate these values aids system designers in the refinement of syndrome definitions to better meet public health needs. Utilizing a stratified sampling method and expert review to create a gold standard dataset for the calculation of sensitivity and specificity, we describe how varying syndrome structure impacts these statistical parameters and discuss the relevance of this to outbreak detection and investigation.


High Frequency of Post-Transfusion Microchimerism Among Multi-Transfused Beta-Thalassemic Patients.
Transfusion-associated microchimerism implies the presence of allogeneic hematopoietic cells in an individual, following the transfusion of a blood product. It is a transfusion-related adverse effect/long-term consequence, which has not been well-investigated among regularly transfused patients with thalassemia. We investigated 64 regularly transfused, homozygous β-thalassemic patients and 21 never-transfused healthy volunteer blood donors (controls) for the presence of microchimerism in their sera, using real-time PCR targeting circulating allogeneic, both, Human Leukocyte Antigen-DR isotype (HLA-DR) and non-HLA alleles. The investigation was longitudinally repeated in patient subsets for more than 2 years. Results were correlated with clinical and laboratory parameters, peripheral blood lymphocyte immunophenotype, blood storage time, and donor's gender to identify potential contributing factors for microchimerism generation. Overall, microchimerism was detected in 52 of the 64 patients (81.2%) and in 6 of the 21 controls (28.5%, p = 0.0001). Forty-four patients (68.7%) exhibited long-term microchimerism (persisted for more than 6 months), confirmed at all time-points investigated. Microchimerism was more frequent among elderly, women, splenectomized and more heavily transfused patients, and among those who exhibit higher serum ferritin levels. In these patients, a distinct descending pattern of CD16dim+CD56dim+ natural killer (NK)-cells (p < 0.001) and an ascending pattern of CD4+CD25brightCD127- regulatory T-cells (p = 0.022) for increasing allelic burden were noticed, suggesting the establishment of recipient immune tolerance against the donor-derived chimeric alleles. Both splenectomized and non-splenectomized thalassemic patients exhibited the same trend. The storage time of transfused blood products and donor/gender mismatch had no impact on the development of microchimerism. Transfusion-associated microchimerism appears to be a very common complication among multi-transfused thalassemic patients. The potential clinical consequences of this phenomenon remain as yet unclear. Immune tolerance attributed to disease itself and to repeated transfusions might at least in part explain its appearance.


To Be Continued? Long-Term Treatment Effects of Antidepressant Drug Classes and Individual Antidepressants on the Risk of Developing Dementia: A German Case-Control Study.
Given the need for disease-modifying therapies for dementia, drug repurposing appears to be a promising approach, at least as a risk reduction treatment. Preclinical studies suggest that antidepressants-in particular selective serotonin reuptake inhibitors-have beneficial effects on dementia-related biomarkers and functional outcomes, although clinical data are inconclusive. The present case-control study aimed to evaluate the effects of antidepressant drug classes and individual compounds with different treatment durations on the risk of developing dementia. Analyses are based on data from the German Disease Analyzer database (owned and maintained by IQVIA) and included 62,317 subjects with an incident dementia diagnosis (ICD-10: F01, F03, G30, F06.7) and controls matched by age, sex, and physician between January 2013 and December 2017. Logistic regression analyses adjusting for health insurance status and comorbid diseases associated with dementia or antidepressant use were performed to investigate the association between dementia incidence and treatment with 4 major antidepressant drug classes and 14 of the most frequently prescribed individual substances. In 17 of 18 comparisons, long-term treatment (≥ 2 years) with any antidepressant was associated with a lower incidence of dementia than short-term treatment. Tricyclic and herbal antidepressants were associated with a decrease in dementia incidence, especially with long-term treatment. The lowest risks for dementia on an individual substance basis were identified for long-term treatment with escitalopram (odds ratio [OR] = 0.66; 95% CI, 0.50-0.89) and Hypericum perforatum (OR = 0.6; 95% CI, 0.51-0.70). Long-term treatment with tricyclic antidepressants, Hypericum perforatum, or escitalopram may be associated with reduced incidence of dementia. If antidepressant therapy is well tolerated, continuation-even if depressive symptoms have resolved-may be considered even beyond the purpose of relapse prevention. Future combined analyses of multinational registries and long-term clinical trials are needed to substantiate these findings.


Tiny or Tall, Mighty or Small-Music for All! Developing an Interactive Online Storybook to Promote Body Positivity in Children.
Body dissatisfaction and dietary restraint have been demonstrated in children as young as 5 years. Internalization of a thin-ideal is theorized to occur before the onset of body dissatisfaction and both have the potential to influence self-worth and impact multiple aspects of life. Across childhood, body dissatisfaction tends to increase while there is a parallel decline in positive self-concepts. Social comparisons also become more critical after the age of 7 years. Research suggests that early childhood (aged 3-8 years) may be the ideal time to expose children to content that counters unhealthy, unrealistic media ideals about body shape and size. This Practice Note describes the process of creating an evidence-based online storybook, Tiny or Tall, Mighty or Small-Music for All!, written to promote positive body image in children. Multiple steps were taken to complete this project, which required collaboration among experts across fields of public health, children's literature, and music. The storybook can be downloaded as a PDF file for free, online, and integrates sound clips for each instrument to more fully engage readers. We hope that this electronic platform overcomes potential logistical and financial barriers of accessing a print copy and therefore allows the message of body positivity to reach a wider audience.


Relations of body mass index and coronary risk as estimated by the Framingham Risk Score.
The Framingham Risk Score is considered to predict 10-yr. risk of developing coronary heart disease. Other risk factors, such as a family history of coronary heart disease, sedentary lifestyle, and obesity should also be considered when estimating the risk of development of coronary heart disease. The last two factors can be modified by therapeutic lifestyle alterations. This cross-sectional coronary risk assessment of 16,871 Japanese subjects was estimated by the Framingham Risk Score. Sex and age were included in the calculation of the Framingham Risk Score. When multiple regression analysis was conducted controlling for age, regular physical exercise, smoking, and drinking, the body mass index was significantly associated with the Framingham Risk Score. The standardized regression coefficients for body mass index were .271 in men (p < .001) and .211 in women (p < .001), respectively. The significant association of body mass index with coronary heart disease risk, as estimated by the Framingham Risk Score, confirmed prior work.


Contribution of astrocytes to neuropathology of neurodegenerative diseases.
Classically, the loss of vulnerable neuronal populations in neurodegenerative diseases was considered to be the consequence of cell autonomous degeneration of neurons. However, progress in the understanding of glial function, the availability of improved animal models recapitulating the features of the human diseases, and the development of new approaches to derive glia and neurons from induced pluripotent stem cells obtained from patients, provided novel information that altered this view. Current evidence strongly supports the notion that non-cell autonomous mechanisms contribute to the demise of neurons in neurodegenerative disorders, and glia causally participate in the pathogenesis and progression of these diseases. In addition to microglia, astrocytes have emerged as key players in neurodegenerative diseases and will be the focus of the present review. Under the influence of pathological stimuli present in the microenvironment of the diseased CNS, astrocytes undergo morphological, transcriptional, and functional changes and become reactive. Reactive astrocytes are heterogeneous and exhibit neurotoxic (A1) or neuroprotective (A2) phenotypes. In recent years, single-cell or single-nucleus transcriptome analyses unraveled new, disease-specific phenotypes beyond A1/A2. These investigations highlighted the complexity of the astrocytic responses to CNS pathology. The present review will discuss the contribution of astrocytes to neurodegenerative diseases with particular emphasis on Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and frontotemporal dementia. Some of the commonalties and differences in astrocyte-mediated mechanisms that possibly drive the pathogenesis or progression of the diseases will be summarized. The emerging view is that astrocytes are potential new targets for therapeutic interventions. A comprehensive understanding of astrocyte heterogeneity and disease-specific phenotypic complexity could facilitate the design of novel strategies to treat neurodegenerative disorders.


Development of potent ALK inhibitor and its molecular inhibitory mechanism against NSCLC harboring EML4-ALK proteins.
Here, we show the newly synthesized and potent ALK inhibitor having similar scaffold to KRCA-0008, which was reported previously, and its molecular mechanism against cancer cells harboring EML4-ALK fusion protein. Through ALK wild type enzyme assay, we selected two compounds, KRCA-0080 and KRCA-0087, which have trifluoromethyl instead of chloride in R2 position. We characterized these newly synthesized compounds by in vitro and in vivo assays. Enzyme assay shows that KRCA-0080 is more potent against various ALK mutants, including L1196M, G1202R, T1151_L1152insT, and C1156Y, which are seen in crizotinib-resistant patients, than KRCA-0008 is. Cell based assays demonstrate our compounds downregulate the cellular signaling, such as Akt and Erk, by suppressing ALK activity to inhibit the proliferation of the cells harboring EML4-ALK. Interestingly, our compounds induced strong G1/S arrest in H3122 cells leading to the apoptosis, which is proved by PARP-1 cleavage. In vivo H3122 xenograft assay, we found that KRCA-0080 shows significant reduction in tumor size compared to crizotinib and KRCA-0008 by 15-20%. Conclusively, we report a potent ALK inhibitor which shows significant in vivo efficacy as well as excellent inhibitory activity against various ALK mutants.


Computer simulation of dementia care demand heterogeneity using hybrid simulation methods: improving population-level modelling with individual patient decline trajectories.
The aim of the study was to model dementia prevalence and outcomes within an ageing population using a novel hybrid simulation model that simultaneously takes population-level and patient-level perspectives to better inform dementia care service planning, taking into account severity progression variability. This is a simulation study. We developed a hybrid computer simulation combining different methods to best represent population and individual dementia dynamics. Individual patient outcomes are aggregated into three progression rate types to report the effects of severity progression variability and intervention benefits. Fast progression of dementia severity is associated with higher annual care cost and short overall survival duration. Those patients are more likely to develop moderate to severe symptoms more quickly, highlighting a need for more urgent provision of appropriate care services. Slower severity progression is associated with lower annual care costs, but longer survival requires higher overall financial provision. Although lifestyle interventions reduce overall care costs, treatment and lifestyle intervention benefits are modest at the population level. Individual variation of dementia decline is an important factor to include in planning adequate levels of care services and to ensure timely and appropriate service availability. Hybrid simulation models provide useful insights at the population and individual level, supporting effective decision-making.


Corneal sensitivity after topical bromfenac sodium eye-drop instillation.
To evaluate the safety of bromfenac sodium eye drops from the standpoint of corneal sensitivity and tear secretion in healthy controls following instillation for 1 month. A prospective single-blind parallel clinical study was conducted in 20 eyes of ten healthy volunteers with no history of ocular or systemic allergic disease, dry eye, contact lens wear, or ocular surgery. Participants were instructed to instill either bromfenac sodium or artificial tears in each eye twice daily for 28 days. Corneal sensitivity tested using a Cochet-Bonnet esthesiometer was evaluated before and immediately after instillation at 7, 14, and 28 days after the initiation of treatment. Tear secretion was also evaluated by Schirmer's eye test before and at 28 days. No significant difference in mean corneal sensitivity and tear-secretion rate was observed between the bromfenac and artificial-tear treatment groups at any time. These results indicate that bromfenac sodium eye drops are safe with respect to corneal sensitivity and tear secretion in subjects with a normal ocular surface condition. Further evaluation is still necessary to determine whether bromfenac is safe in pathological conditions, such as inflammatory disorders and postsurgical cases.


The mission of the cochrane anesthesia review group: preparing and disseminating systematic reviews of the effect of health care in anesthesiology.
This article illustrates the basic principles of evidence-based medicine and the work within the Cochrane Collaboration and the Cochrane Anesthesia Review Group. It describes how important randomized controlled trials and systematic reviews are in providing the best evidence to answer clinically relevant questions.


Kinetics of glucose decarboxylation in the substrate-limited isolated perfused kidney.
Rat kidneys were perfused with a cell-free perfusate containing substrate-free albumin, different glucose concentrations (0.20-5.0 mmol/l), and uniformly labeled 14C-glucose. The rate of glucose decarboxylation (Qox), as a function of [glucose]p, displayed saturation kinetics [Vmax = 0.35 mumol/(g.min); Km = 0.87 mmol/l]; saturation occurred at [glucose]p = 1.0-2.0 mmol/l. Although the presence of as low as 0.2 mmol/l of glucose significantly increased fractional sodium reabsorption (%TNa), there was no correlation between [glucose]p or Qox and % TNa. However, free water clearance (CH2O or CH2O/GFR) was directly proportional to [glucose]p and independent of Qox. We conclude that (1) in the absence of other substrates, renal glucose Qox saturates at hypoglycemic levels of glucose and (2) glucose plays an important role in the generation of solute-free water, a role that is unrelated to glucose Qox.


Glomerular permeability. Ultrastructural studies in experimental nephrosis using horseradish peroxidase as a tracer.
Wistar/Furth rats were made nephrotic by daily administration of amino-nucleoside of puromycin, and the ultrastructural localization of horseradish peroxidase (mol wt 40,000) in the renal glomerulus was studied from 1 min to 20 hr after intravenous injection of the tracer. In control rats, peroxidase permeated the endothelial fenestrae, the basement membrane, and the epithelial slits, and was present in tubular lumina. Nephrotic glomeruli showed relatively normal basement membranes, extensive fusion of foot processes with formation of "close" intercellular junctions, and large vacuoles and pockets in epithelial cells. On serial sections some of the epithelial vacuoles communicated on one side with the extracellular space overlying basement membrane, and on the other side with the urinary space. In nephrotic animals, peroxidase permeated the basement membrane and the close junctions, and was present in many of the vacuoles and pockets as early as 1 min after injection. Only small numbers of peroxidase-positive vacuoles remained in. epithelial cells 1 hr or more after injection of the tracer. It is suggested that the epithelial pockets and vacuoles form pathways across which leaking proteins can be transferred across the epithelium into the urinary space. Epithelial vacuoles may also be absorption droplets designed to "conserve" leaking proteins, but this function was not prominent in our experiments with peroxidase.


Transcriptome-Based Identification of Genes Responding to the Organophosphate Pesticide Phosmet in Danio rerio.
Organophosphate pesticides (OPPs) are one of the most widely used insecticides. OPPs exert their neurotoxic effects by inhibiting acetylcholine esterase (AChE). Most of the gross developmental abnormalities observed in OPP-treated fish, on the other hand, may not be explained solely by AChE inhibition. To understand the overall molecular mechanisms involved in OPP toxicity, we used the zebrafish (ZF) model. We exposed ZF embryos to an OPP, phosmet, for 96 h, and then analyzed developmental abnormalities and performed whole transcriptome analysis. Phenotypic abnormalities, such as bradycardia, spine curvature, and growth retardation, were observed in phosmet-treated ZF (PTZF). Whole transcriptome analysis revealed 2190 differentially expressed genes (DEGs), with 822 and 1368 significantly up-and downregulated genes, respectively. System process and sensory and visual perception were among the top biological pathways affected by phosmet toxicity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed significant enrichment of metabolic pathways, calcium signaling pathway, regulation of actin cytoskeleton, cardiac muscle contraction, drug metabolism-other enzymes, and phototransduction. Quantitative real-time PCR results of six DEGs agreed with the sequencing data expression profile trend. Our findings provide insights into the consequences of phosmet exposure in ZF, as well as an estimate of the potential risk of OPPs to off-target species.


Impact of long-acting therapies on the global HIV epidemic.
Long-acting antiretroviral drugs have emerged as exciting treatment and preexposure prophylaxis (PrEP) options for people with HIV and at risk of HIV. Long-acting regimens may improve dosing convenience, tolerability and cost compared with current daily-based oral therapy. They can also circumvent stigma associated with oral therapy for both treatment and PrEP, thereby improving adherence and outcomes. Yet, multiple challenges remain, many specific to low-income and middle-income countries (LMICs), where the epidemic is most concentrated and HIV prevention and treatment options are limited. To optimize the use of long-acting formulations, key outstanding questions must be addressed. Uncertain costing, scale-up manufacturing, complex delivery systems and implementation challenges are potential barriers when considering the scalability of long-acting ARVs for global use.


Amyloid-beta oligomers: possible roles as key neurotoxins in Alzheimer's Disease.
Alzheimer's disease is the most common form of senile dementia. Although the amyloid-beta peptide was identified in 1984 as the major constituent of the senile plaques that characterize the disease, accumulating evidence indicates that the plaque density does not correspond well to the concurrent disease state. In order to resolve this disconnect, a number of recent studies have shifted away from the senile plaque and classical fibrillar forms of amyloid toward a less well structured species as the proximate neurotoxic factor underlying cognitive failure in Alzheimer's disease: soluble amyloid-beta peptide oligomer (also known as the amyloid-beta peptide-derived diffusible ligand). Paradoxically, several studies in the last 2 years have shown that picomolar levels of amyloid-beta peptide have neutral activity or perhaps even an essential role in learning and memory. Here we highlight some of the key observations underlying the growing focus on the amyloid-beta peptide oligomer.


Union activity in hospitals: past, present, and future.
Between 1970 and 1980, the percentage of hospitals with one or more collective bargaining contracts increased from 15.7 percent to 27.4 percent. A substantial amount of variation exists in the extent of unionism on the basis of hospital ownership, bed size, and location. Employees are more likely to organize when hospitals in the State are regulated by a mandatory rate-setting program. Unions raise hospital employee's wages--a modal estimate for RNs is about 6 percent; the corresponding figure for nonprofessional employees is about 10 percent. Growth of union activity in hospitals has generally not been a major contributor to hospital wage inflation, and less than 10 percent of the increase in real (relative to the Consumer Price Index) spending for hospital care that occurred during the 1970s can be attributed to union growth. We project that between 45 and 50 percent of all hospitals will have at least one union by 1990.


Knowledge and Attitude Towards Human Papillomavirus Vaccine and Associated Factors Among Mothers Who Have Eligible Daughters in Debre Markos Town, Northwest Ethiopia.
This study aimed to assess knowledge and attitude towards the human papillomavirus vaccine and associated factors among mothers who have eligible daughters. A community-based cross-sectional study with a total sample of 601 study participants was conducted in Debre Markos town from February to March 2021. The study participants were selected using a multistage sampling technique from mothers who have eligible daughters. The data was collected using an interview administration questionnaire. The data were entered into EPI data version 3.1 then, exported to SPSS version 25 for analysis. Variables with a p-value of < 0.25 in bivariate were a candidate for multivariate and those variables with a p-value of <0.05 in multivariate binary logistic regression were considered as a statistically significant factor for knowledge and attitude of the HPV vaccine. A total of 601 study participants with a response rate of 100% were included in the study. Among participants in this study, 47.6% have good knowledge and 77.4% have a positive attitude towards the HPV vaccine. Knowledge of mothers about HPV vaccine was affected by having degree and above (adjusted odds ratio (AOR) =7.687; 95% CI=1.837-32.168; p=0.005), did not hear about HPV vaccine (AOR=0.172; 95% CI=0.098-0.302; P=0.000), and positive attitude towards HPV vaccine (AOR=2.959; 95% CI=1.580-5.539; P=0.001). Attitude of mothers towards HPV vaccine was affected by did not hear about HPV vaccine (AOR=0.285; 95% CI=0.163-0.499; P=000), and good knowledge about HPV vaccine (AOR=2.705; 95% CI=1.454-5.035; 0.002). Knowledge of mothers who have eligible daughters about HPV vaccine was low. Maternal educational level, hearing about the HPV vaccine, and attitude towards HPV vaccine were significantly associated predictors with knowledge towards HPV vaccine. However, the attitude was high and factors associated with attitudes towards the HPV vaccine were knowledge about the HPV vaccine and hearing about the HPV vaccine. An integrated work should be considered by Debre Markos town health office with other non-governmental organizations working on health and health-related issues to improve knowledge about the importance of HPV vaccine for mothers who have eligible daughters.


The histopathological effects of thiodan on the liver and gut of mosquitofish, Gambusia affinis.
Thiodan (33.7% endosulfan), a polychlorinated cyclodiene insecticide, was evaluated for its histopathological effects on mosquitofish, Gambusia affinis, by light microscopy. Fish were exposed to doses of 0.00 (control), 1.00, 2.50, and 5.00 microg/L on days 7, 14, 21, and 30. No histopathological effects were apparent at control group. The histopathological alterations were characterized as oedema, degeneration, accumulation of lymphocytes in the lamina propria, disintegration of villuses, pycnotic state of nuclei, and necrosis in gut; degeneration, hypertrophy, sinusoids enlargement, hemorrhage, pycnosis position of nuclei, vacuolization of cell cytoplasm, infiltration of mononuclear lymphocyte, and congestion in liver. These alterations were time- and dose-dependent.


Functional analysis of patients who have had a modified Van Nes rotationplasty.
Electromyographic analysis of gait in eight patients who had had a modified Van Nes rotationplasty was performed to compare the activity of the flexors and extensors of the ankle on the side of the operation with that of the flexors and extensors of the knee on the normal, contralateral side. The resemblance in the activity of the extensors was more pronounced than that of the flexors. In three patients, the angle of flexion of the knee throughout the gait cycle was the same on the side of the rotationplasty as on the normal side. There was more symmetry in the swing phase than has been reported for patients who have had an above-the-knee amputation. The strength of the dorsiflexors of the ankle on the side of the rotationplasty was 68 percent and that of the flexors was 71 per cent when compared with that of the muscles of the normal ankle.


[Mesenteric vein thrombosis following percutaneous transhepatic portal vein catheterization for the localization of an insulinoma].
The authors report on a fatal mesenteric vein thrombosis following an uncomplicated percutaneous transhepatic portal vein catheterisation for the localisation of an insulinoma. Several hours after the procedure the patient developed an acute abdomen. An emergency laparotomy revealed a haemorrhagic infarct of the ileum. The resected specimen showed an acute phlebitis with fresh thrombus. The cause of the phlebothrombosis was thought to be intimal damage from high osmolar contrast medium. There was no evidence of damage due to the catheter, either on the phlebogram or pathologically.


Coagulation Laboratory Testing Is Predictive of Wound Complications Following Microdiscectomy.
Retrospective review. To determine whether abnormal preoperative testing is associated with postoperative complications in patients undergoing a microdiscectomy. Patients undergoing a microdiscectomy between 2006 and 2013 were identified in the National Surgical Quality Improvement Program database based on appropriate current procedural terminology coding. Thirty-day postoperative complications were analyzed in addition to patient demographics, comorbidities, and abnormal preoperative laboratory values. A series of over 650 univariate analyses to determine which independent variables to include for each complication were completed. Based on those analyses, 12 logistic regression models were built, one for each specific complication. Each model adjusted for age, gender, comorbidities, American Society of Anesthesiologists classification, as well as operative time. A total of 5947 patients undergoing a microdiscectomy were included in the study. Abnormal preoperative international normalized ratio (odds ratio [OR] = 5.85, P < .05) was associated with any wound infection, superficial or deep, and abnormal partial thromboplastin time was significantly associated with wound dehiscence (OR = 6.80, P < .05). Postoperative urinary tract infections were associated with abnormal preoperative hematocrit (OR = 8.00, P < .05). None of the identified preoperative labs were independently associated with pulmonary embolism, organ space surgical site infections, or intubation. Abnormal preoperative coagulation labs were significantly associated with postoperative wound complications. However, the majority of tests were not associated with adverse events following microdiscectomy. Further study is necessary to conclude whether these tests provide information that can modify perioperative management and whether widespread testing is cost-effective.


Genome-wide differences in gene expression and alternative splicing in developing embryo and endosperm, and between F1 hybrids and their parental pure lines in sorghum.
Developing embryo and endosperm of sorghum show substantial and multifaceted differences in gene expression and alternative splicing, which are potentially relevant to heterosis. Differential regulation of gene expression and alternative splicing (AS) are major molecular mechanisms dictating plant growth and development, as well as underpinning heterosis in F1 hybrids. Here, using deep RNA-sequencing we analyzed differences in genome-wide gene expression and AS between developing embryo and endosperm, and between F1 hybrids and their pure-line parents in sorghum. We uncover dramatic differences in both gene expression and AS between embryo and endosperm with respect to gene features and functions, which are consistent with the fundamentally different biological roles of the two tissues. Accordingly, F1 hybrids showed substantial and multifaceted differences in gene expression and AS compared with their pure-line parents, again with clear tissue specificities including extents of difference, genes involved and functional enrichments. Our results provide useful transcriptome resources as well as novel insights for further elucidation of seed yield heterosis in sorghum and related crops.


Dynamics of the Kitaev-Heisenberg Model.
We introduce a matrix-product state based method to efficiently obtain dynamical response functions for two-dimensional microscopic Hamiltonians. We apply this method to different phases of the Kitaev-Heisenberg model and identify characteristic dynamical features. In the ordered phases proximate to the spin liquid, we find significant broad high-energy features beyond spin-wave theory, which resemble those of the Kitaev model. This establishes the concept of a proximate spin liquid, which was recently invoked in the context of inelastic neutron scattering experiments on α-RuCl_{3}. Our results provide an example of a natural path for proximate spin liquid features to arise at high energies above a conventionally ordered state, as the diffuse remnants of spin-wave bands intersect to yield a broad peak at the Brillouin zone center.


Pressurized liquid extraction followed by LC-ESI/MS for analysis of four chromones in Radix Saposhnikoviae.
An efficient pressurized liquid extraction (PLE) technique was employed in extracting chromones from the roots of Saposhnikovia divaricata (Radix Saposhnikoviae). Chromones were quantified and analyzed by LC-ESI/MS. The PLE procedure was optimized, validated and compared with the other conventional extraction techniques. PLE gained the best result due to the highest extraction efficiency within the shortest extraction time. The optimal conditions of PLE were employing 50% ethanol as the extraction solvent at a temperature of 140°C and an extraction pressure of 1500 psi, using one extraction cycle with a static extraction time of 8 min. A good LC separation was achieved using a Hypersil ODS2 column and methanol/water as the mobile phase at a flow rate of 0.8 mL/min. MS coupling with an ESI interface in the positive ion mode was used as the detection technique. This is the first report on combining PLE with LC-ESI/MS for the extraction and quantification of chromones in Radix Saposhnikoviae. The elaborated PLE method also provided a good alternative for the chromone extraction from other plant substances.


Prospective longitudinal comparative study of health-related quality of life in patients treated with radical prostatectomy or permanent brachytherapy for prostate cancer.
To determine health-related quality of life (HRQOL) after radical retropubic prostatectomy (RRP) or permanent prostate brachytherapy (BT), third party-conducted QOL surveys were prospectively compared. Between 2004 and 2005, 37 patients underwent RRP and 36 were treated with BT. A QOL survey consisting of the Medical Outcomes Study 36-Item Short Form (SF-36), the University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) and the International Prostate Symptoms Score (IPSS) was completed prospectively by a research coordinator at baseline, and at 1, 3, 6 and 12 months after treatment. The RRP patients scored well in general QOL except at 1 month after surgery, with their mental health better than at baseline by 6 months after surgery. Disease-specific QOL in RRP patients received a low score at 1 month for both urinary and sexual function, though urinary function rapidly recovered to baseline levels. BT patient QOL was not affected by the therapy except in the IPSS score. However, general and mental health scores in BT patients were inferior to those in RRP patients. This prospective study revealed differences in QOL after RRP and BT. These results will be helpful in making treatment decisions.


[Adhesion of sulphate-reducing bacteria to steel under cathode polarization].
Adhesion of different (as to their corrosion aggression) strains of sulphate-reducing bacteria to steel has been studied under cathode polarization at various potentials: -800, -900, -1000, -1200 mV. It has been established that cathode polarization differently affects the adhesion of strain of sulphate-reducing bacteria with various aggression to steel. Correlation between the bacterial strains aggression and the number of cells adhered to metal have been noted. The cells of aggressive strains of D. indonensis Indonesia and Desulfovibrio sp. Kiev-10 adhered to metal most actively at cathode depolarization (8.0 x 10(7) and 3.5 x 10(7) cell/cm2, respectively). Nonaggressive strains of bacteria D. desulfuricans Kiev-45 and Desulfobulbus sp. Portsmouth adhered to metal in a less quantity. The data obtained prove that the use of cathode protection without allowance for the microbe factor can lead to intensification of the corrosion process.


Multifractal detrended fluctuation analysis to characterize phase couplings in seahorse (Hippocampus kuda) feeding clicks.
Nonlinear phenomena in animal vocalizations fundamentally includes known features, namely, frequency jump, subharmonics, biphonation, and deterministic chaos. In the present study, the multifractal detrended fluctuation analysis (MFDFA) has been employed to characterize the phase couplings revealed in the feeding clicks of Hippocampus kuda yellow seahorse. The fluctuation function Fq(s), generalized Hurst exponent h(q), multifractal scaling exponent τ(q), and the multifractal spectrum f(α) calculated in the procedure followed were analyzed to comprehend the underlying nonlinearities in the seahorse clicks. The analyses carried out reveal long-range power-law correlation properties in the data, substantiating the multifractal behavior. The resulting h(q) spectrum exhibits a distinct characteristic pattern in relation to the seahorse sex and size, and reveals a spectral blind spot in the data that was not possible to detect by conventional spectral analyses. The corresponding multifractal spectrum related width parameter Δh(q) is well clustered, defining the individual seahorse clicks. The highest degree of multifractality is evident in the 18 cm male seahorse, signifying greater heterogeneity. A further comparison between the seahorse body size and weight (wet) with respect to the width parameter Δh(q) and the second-order Hurst exponent h(q=2) underscores the versatility of MFDFA as a robust statistical tool to analyze bioacoustic observations.


An activation domain in the C-terminal subunit of HCF-1 is important for transactivation by VP16 and LZIP.
In herpes simplex virus, lytic replication is initiated by the viral transactivator VP16 acting with cellular cofactors Oct-1 and HCF-1. Although this activator complex has been studied in detail, the role of HCF-1 remains elusive. Here, we show that HCF-1 contains an activation domain (HCF-1(AD)) required for maximal transactivation by VP16 and its cellular counterpart LZIP. Expression of the VP16 cofactor p300 augments HCF-1(AD) activity, suggesting a mechanism of synergy. Infection of cells lacking the HCF-1(AD) leads to reduced viral immediate-early gene expression and lowered viral titers. These findings underscore the importance of HCF-1 to herpes simplex virus replication and VP16 transactivation.


Possible association of decreased NKG2D expression levels and suppression of the activity of natural killer cells in patients with colorectal cancer.
Natural-killer group 2 (NKG2), a natural killer (NK) cell receptor, plays a critical role in regulating NK cytotoxicity. In this study, we investigated the expression levels of natural killer group 2 member A (NKG2A) and natural killer group 2 member D (NKG2D) in NK cells as well as the regulatory function of NKG2D in patients with colorectal cancer (CRC). Sixty-two CRC patients and 32 healthy controls were enrolled in this study. The expression levels of NKG2A and NKG2D mRNA in peripheral blood mononuclear cells (PBMCs) were investigated using real-time PCR. Flow cytometry was performed to assay the levels of NKG2A and NKG2D proteins in NK cells. The levels of NKG2D mRNA in PBMCs in the patients were significantly lower than those in the controls [mean ± SD, 1.11 ± 0.60 (CRC patients) vs. 1.65 ± 0.71 (healthy controls); p < 0.01], whereas the 2 groups showed no apparent difference in the levels of NKG2A mRNA (p>0.05). In addition, the patients showed significantly lower NKG2D levels in NK cells than the controls did (71.23% ± 8.31% [CRC patients] vs. 79.39% ± 5.58% [healthy controls]; p < 0.01). However, we observed no distinct difference in the NKG2A expression levels in NK cells between the 2 groups (p> 0.05). Notably, blockage of NKG2D signaling with anti-NKG2D antibodies ex vivo resulted in decreased cytotoxicity and CD107a degranulation. Our data revealed that the decrease in NKG2D expression levels may have been associated with suppression of NK cell activity in CRC patients.


Differential characterization of human coronary collateral blood flow velocity.
The functional importance and protective nature of the coronary collateral circulation has been well established. There are few data, however, regarding the phasic nature and absolute velocities of collateral flow in patients. The aim of this study was to characterize and quantify ipsilateral coronary collateral blood flow velocity in patients during coronary angioplasty. Coronary collateral flow velocity was measured in 49 patients during coronary angioplasty. Angiographic collateral filling was categorized by the Rentrop grading scale (0 to 3) and by anatomic pathway (epicardial, intramyocardial, or unknown [acutely recruited]). Collateral blood flow velocity was measured with a Doppler-tipped guide wire placed distal to the balloon occlusion in the collateralized vessel. Collateral flow velocity was characterized as predominantly systolic or diastolic, and phasic flow patterns were defined as biphasic (both systolic and diastolic), monophasic (only systolic or diastolic), or bidirectional (antegrade and retrograde velocity). Twenty-three (47%) patients had biphasic flow; 17 (35%) patients had monophasic flow; and 9 (18%) patients had bidirectional flow. Thirty-six (73%) of 49 patients had predominantly systolic flow signals. Epicardial collateral pathways had the highest total flow velocity integral, at 15.0 +/- 7.0 (vs intramyocardial [8.4 +/- 5.7] and acutely recruitable [5.4 +/- 2.1]; p < 0.05). There were no differences in flow velocity integrals among the Rentrop angiographic grades of collateral filling. These data establish three patterns of coronary collateral blood flow and demonstrate that the majority of collateral flow in the ipsllateral receiving vessel occurs during systole. The measurement of coronary collateral flow velocity provides a unique means to study the effects of pharmacologic or mechanical interventions on human collateral blood flow.


Emerging Bcl-2 inhibitors for the treatment of cancer.
Bcl-2 family proteins are a component of the antiapoptotic machinery and are overexpressed in different malignancies. Accordingly, their enhanced expression has been attributed to the observed chemoresistance in most of the cancers. Therefore, targeting Bcl-2 family members becomes an important and attractive approach towards cancer therapy and is currently a very rapidly evolving area of research. This article highlights the numerous advancements that have been made in the design and synthesis of small molecule inhibitors (SMI) of pro-survival Bcl-2 proteins. This review comprehensively describes the progress made over the last 2 decades on this subject, including the clinical status of SMIs of Bcl-2 family proteins. Newer insights on the status of our knowledge on SMIs of Bcl-2 family proteins, their most beneficial application as well as current and future directions in this field are discussed. Targeting Bcl-2 family proteins using SMI strategies is gaining momentum, with the emergence of certain new classes of inhibitors in Phase I and II clinical settings. In view of the tremendous progress toward the development of such inhibitors, this innovative approach certainly holds promise and has the potential to become a future mainstay for cancer therapy. The stage is set for the next generation of SMIs, for not only Bcl-2 proteins but also for Mcl-1. Other emerging molecules in the apoptotic machinery will also be explored and targeted.


Integrative analysis identifies activated anti-tumor immune microenvironment in lung metastasis of pancreatic cancer.
Although the prognosis of patients experiencing recurrences after surgery for pancreatic cancer is extremely poor, patients who develop recurrence in the lung have a better prognosis compared to other types of recurrence. We performed a histo-immunological analysis of the metastatic specimens to identify specific features of this patient subgroup. We performed immunohistochemistry for CD4+, CD8+, CD45RO+, Foxp3, and PD-L1 in the lung (n = 22), peritoneal (n = 18), and liver (n = 6) metastases of pancreatic cancer. As microenvironmental and immunonutritional investigations, the tumor-stroma ratio and prognostic nutritional index (PNI) were utilized in the integrative analysis of immunological features. We identified significantly increased tumor-infiltrating CD4+, CD8+, and CD45RO+ cells in lung metastasis, compared with peritoneal and liver metastases (lung vs. peritoneum/liver, CD4: P < 0.001/P = 0.015, CD8: P < 0.001/P = 0.038, CD45RO: P = 0.022/P = 0.012). The CD8/Foxp3 ratio was higher in the lung than in the liver (P = 0.024). PD-L1 expression was significantly higher in lung metastasis than in peritoneal metastasis (P = 0.010). Furthermore, we found that lung metastasis had fewer cancer stroma than peritoneal metastasis (P < 0.001). A higher PNI was observed in patients with lung metastasis, and PNI was positively correlated with tumor-infiltrating lymphocytes in metastatic sites. We identified that lung metastasis revealed an immunologically "hot" tumor with increased TILs and PD-L1 expression. This specific feature suggests that patients with lung metastasis can be candidates for immunotherapy, such as immune checkpoint inhibitors; therefore, our study provides a framework for developing individualized treatment strategies for this patient subgroup.


Constructing a Novel Electroluminescent Device with High-Temperature and High-Humidity Resistance based on a Flexible Transparent Wood Film.
Plastic-based electroluminescent devices generally suffer from thermal expansion owing to the high coefficient of thermal expansion (CTE) of the plastic substrate, which reduces the service lifetime of the electroluminescent device. In this study, we employed a delignified veneer synergistically reinforced with epoxy resin as a low-cost substrate for alternating current electroluminescent (ACEL) devices. In brief, the natural interconnected porous structure of wood had a good antideformation capacity to restrict the volume expansion of the epoxy resin under thermal conditions. Furthermore, the impregnation of epoxy resin dramatically improved the optical transmittance of delignified veneer. Considering its low CTE and antideformation capability, the intrinsically high-temperature and high-humidity resistance device based on transparent sliced veneer (TSV) was constructed. Remarkably, the TSV-ACEL device exhibited excellent stability and maintained good luminescence performance even at a high temperature (100 °C, 30 min; as a reference, the poly(ethylene terephthalate)-based ACEL device has stopped operating), completely submerged in water (30 min), or under high-temperature and high-humidity conditions (90 °C, relative humidity: >90%, 30 min). These results pave the way for the realization of flexible and high-temperature resistance ACEL devices.


Association of County-level Upward Economic Mobility with Stage at Diagnosis and Receipt of Treatment Among Patients Diagnosed with Pancreatic Adenocarcinoma.
Determining the impact of county-level upward economic mobility on stage at diagnosis and receipt of treatment among Medicare beneficiaries with pancreatic adenocarcinoma. The extent to which economic mobility contributes to socioeconomic disparities in health outcomes remains largely unknown. Pancreatic adenocarcinoma patients diagnosed in 2004-2015 were identified from the SEER-Medicare linked database. Information on countylevel upward economic mobility was obtained from the Opportunity Atlas. Its impact on early-stage diagnosis (stage I or II), as well as receipt of chemotherapy or surgery was analyzed, stratified by patient race/ethnicity. Among 25,233 patients with pancreatic adenocarcinoma, 37.1% (n = 9349) were diagnosed at an early stage; only 16.7% (n = 4218) underwent resection, whereas 31.7% (n = 7996) received chemotherapy. In turn, 10,073 (39.9%) patients received any treatment. Individuals from counties with high upward economic mobility were more likely to be diagnosed at an earlier stage (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.07-1.25), as well as to receive surgery (OR 1.58, 95% CI 1.41-1.77) or chemotherapy (OR 1.51, 95% CI 1.39-1.63). White patients and patients who identified as neither White or Black had increased odds of being diagnosed at an early stage (OR 1.12, 95% CI 1.02-1.22 and OR 1.35, 95% CI 1.02-1.80, respectively) and of receiving treatment (OR 1.73, 95% CI 1.59-1.88 and OR 1.49, 95% CI 1.13-1.98, respectively) when they resided in a county of high vs low upward economic mobility. The impact of economic mobility on stage at diagnosis and receipt of treatment was much less pronounced among Black patients (high vs low, OR 1.28, 95% CI 0.96-1.71 and OR 1.30, 95% CI 0.99-1.72, respectively). Pancreatic adenocarcinoma patients from higher upward mobility areas were more likely to be diagnosed at an earlier stage, as well as to receive surgery or chemotherapy. The impact of county-level upward mobility was less pronounced among Black patients.


Abortion, infanticide and moral context.
In 'After-birth abortion: why should the baby live?', Giubilini and Minerva argue that infanticide should be permitted for the same reasons as abortion. In particular, they argue that infanticide should be permitted even for reasons that do not primarily serve the interests (or would-be best interests) of the newborn. They claim that abortion is permissible for reasons that do not primarily serve the interests (or would-be interests) of the fetus because fetuses lack a right to life. They argue that newborns also lack a right to life, and they conclude that therefore, the same reasons that justify abortion can justify infanticide. This conclusion does not follow. The lack of a right to life is not decisive. Furthermore, the justificatory power of a given reason is a function of moral context. Generalisations about reasons across dissimilar moral contexts are invalid. However, a similar conclusion does follow-that fetus-killing and newborn-killing are morally identical in identical moral contexts-but this conclusion is trivial, since fetuses and newborns are never in identical moral contexts.


Gaining Confidence in the Elusive Histidine Phosphoproteome.
Recent technological advances have made it possible to investigate the hitherto rather elusive protein histidine phosphorylation. However, confident site-specific localization of protein histidine phosphorylation remains challenging. Here, we address this problem, presenting a mass-spectrometry-based approach that outperforms classical HCD fragmentation without compromising sensitivity. We use the phosphohistidine immonium ion as a diagnostic tool as well as ETD-based fragmentation techniques to achieve unambiguous identification and localization of histidine-phosphorylation sites. The work presented here will allow more confident investigation of the phosphohistidine proteome to reveal the roles of histidine phosphorylation in cellular signaling events.


Peroxidative stress and antioxidant enzymes in children with beta-thalassemia major.
Regular blood transfusions and secondary iron overload make thalassemic erythrocytes prone to peroxidative injury. Although some reports suggest endogenous free radical damage in thalassemia, there remains discrepancy in the status of antioxidant enzymes. The aim of this study was to evaluate the extent of lipid peroxidation and status of antioxidant enzyme in children with beta-thalassemia. Fifty transfusion-dependent beta-thalassemics were subjected to analysis of lipoperoxides as malondialdehyde (MDA), nitric oxide (NOx), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GPx) along with serum iron and ferritin, liver functions and uric acid. Plasma MDA was analyzed to indicate the oxidative parameters, whereas the erythrocyte SOD, GPx, and plasma NOx were measured to show the antioxidant status of the children. All these parameters in 30 non-anemic healthy controls attending the child health promotion clinic of hospital were also studied. All the patients were iron overloaded. Markers of free radical injury such as MDA and antioxidant enzyme SOD and NOx levels were significantly elevated in thalassemic children while mean GPx levels were decreased in patients compared to controls (P < 0.001). All these markers significantly correlated with serum ferritin levels. There was no significant difference in levels of GSH measured but it correlated with serum iron levels. Our study results suggest that iron overload causes peroxidative damage in beta-thalassemia and antioxidant systems try to compensate for reducing lipid peroxidation to lower tissue damage.


Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus - United States, May 2013-August 2016.
Candida auris, an emerging fungus that can cause invasive infections, is associated with high mortality and is often resistant to multiple antifungal drugs. C. auris was first described in 2009 after being isolated from external ear canal discharge of a patient in Japan (1). Since then, reports of C. auris infections, including bloodstream infections, have been published from several countries, including Colombia, India, Israel, Kenya, Kuwait, Pakistan, South Africa, South Korea, Venezuela, and the United Kingdom (2-7). To determine whether C. auris is present in the United States and to prepare for the possibility of transmission, CDC issued a clinical alert in June 2016 informing clinicians, laboratorians, infection control practitioners, and public health authorities about C. auris and requesting that C. auris cases be reported to state and local health departments and CDC (8). This report describes the first seven U.S. cases of C. auris infection reported to CDC as of August 31, 2016. Data from these cases suggest that transmission of C. auris might have occurred in U.S. health care facilities and demonstrate the need for attention to infection control measures to control the spread of this pathogen.


Surgical resection for hepatocellular carcinoma.
The result of liver resection for symptomatic hepatocellular carcinoma (HCC) is poor. For Oriental patients, the operative mortality is between 6.7% and 36%. The one-year and five-year survival are 40% and 15% respectively. Coexisting liver cirrhosis is a problem and is responsible for the high operative mortality as well as a significant proportion of late deaths. Technical innovations are being applied to liver resection but further evaluation is necessary to prove their claimed efficacy. Screening of the whole population or high risk individuals enable HCC to be detected early. Most tumours discovered by screening is resectable and the prognosis is better. More efforts should be directed toward improving the accuracy and yield of screening procedures.


Integrating self-efficacy in the cyclical process of paediatric asthma management: a new perspective.
Asthma management consists of a cyclical process based on clinical assessment of the patient, the implementation of therapeutic adjustments, and evaluation of the patient's response. Self-efficacy is the person's confidence in his or her ability to successfully perform a behaviour and guides the patient's decisions for producing healthy behaviours.Studies have shown that asthma management is related to self-efficacy, which in turn can be influenced by various psychosocial factors. A literature search on the relationship between asthma and self-efficacy in paediatric age, has allowed us to hypothesize that adequate levels of self-efficacy might be achieved through a cyclical process, 'the self-efficacy cycle', taking into account assessment, identification of modifiable risk factors and patient's response. This would make it easier to identify the personal and social aspects on which to intervene to promote a proper management of the disease.


An Agent-based Model for Investigating the Effect of Myeloid-Derived Suppressor Cells and its Depletion on Tumor Immune Surveillance.
To predict the behavior of biological systems, mathematical models of biological systems have been shown to be useful. In particular, mathematical models of tumor-immune system interactions have demonstrated promising results in prediction of different behaviors of tumor against the immune system. This study aimed at the introduction of a new model of tumor-immune system interaction, which includes tumor and immune cells as well as myeloid-derived suppressor cells (MDSCs). MDSCs are immune suppressor cells that help the tumor cells to escape the immune system. The structure of this model is agent-based which makes possible to investigate each component as a separate agent. Moreover, in this model, the effect of low dose 5-fluorouracil (5-FU) on MDSCs depletion was considered. Based on the findings of this study, MDSCs had suppressive effect on increment of immune cell number which consequently result in tumor cells escape the immune cells. It has also been demonstrated that low-dose 5-FU could help immune system eliminate the tumor cells through MDSCs depletion. Using this new agent-based model, multiple injection of low-dose 5-FU could eliminate MDSCs and therefore might have the potential to be considered in treatment of cancers.


[Surgical treatment of hypospadias and complications in relation to the child's age].
Hypospadias is one of the most common congenital malformations. Few studies have explored the association of age at time of surgery and the occurrence of complications after hypospadias repair. Determine whether age at hypospadias repair is a risk factor for development of complications. Retrospective cohort of patients with hypospadias repair in one surgical time. The data included: age, type of hypospadias, surgical technique and complications presented. The monitoring was conducted for six months after the surgery. Patients were classified according to age group A less than 24 months, group B from 24 to 48 months and group C over 48 months. We calculated the relative risk and confidence intervals of 95%. 170 patients were included in the analysis. The incidence of complications was 24.1%, the most frequent complication was urethrocutaneous fistula (52.2%). The median age in months of the complication group was 40.8 (6-196), whereas in the group without complications was 37.5 (6-196). Age was not associated with an increased risk for complications, group B (RR= 0.975 [95% CI 0.374-2.547]), and group C (RR= 0.966 [95% CI 0.386-2.416]) when compared with group A. Age at time of surgery for hypospadias correction in one phase is not associated with complications.


Reduction in resting metabolic rate and ratio of plasma leptin to urinary nitric oxide: influence on obesity-related hypertension.
Multiple factors are involved in the pathogenesis of hypertension in the obese individual To evaluate the role of a decrease in sympathetically mediated thermogenesis and the effect of the correlation between the plasma leptin and daily urinary nitric oxide levels on obesity-related hypertension. We evaluated three groups: 25 obese hypertensive patients (age 45.7 +/- 1.37 years, body mass index 34.2 +/- 1.35 kg/m2, systolic/diastolic blood pressure 155 +/- 2.9/105 +/- 1.3, mean arterial pressure 122 +/- 1.50 mmHg); 21 obese normotensive patients (age 39.6 +/- 1.72, BMI 31.3 +/- 0.76, SBP/DBP 124 +/- 2.1/85.4 +/- 1.8, MAP 98.2 +/- 1.80); and 17 lean normotensive subjects (age 38.1 +/- 2.16, BMI 22.1 +/- 0.28, SBP/DBP 117 +/- 1.7/76.8 +/- 1.5, MAP 90.1 +/- 1.50). We determined basal resting metabolic rates, plasma insulin (radio-immunoassay), norepinephrine (high performance liquid chromatography) in all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction diet. At weeks 6 (n = 14) and 14 (n = 10) of the diet the above determinations were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese normotensives, and in 19 obese hypertensives versus 11 obese normotensives, respectively. Obese hypertensive patients had significantly higher basal RMR and plasma NE levels insulin levels were lower in the lean group, with no difference between the hypertensive and normotensive obese groups. At weeks 6 and 14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to values of normotensive subjects. MAP normalized but remained significantly higher than in obese normotensives. Leptin blood levels and the leptin/UNOx ratio were significantly higher in the obese hypertensive compared to the obese normotensive patients. Both these parameters were strongly correlated to BMI, MAP, RMR, and plasma NE and insulin. Obese hypertensive patients excreted less urinary NO metabolites. A strong correlation was found between MAP and the leptin/UNOx ratio. A reduction in sympathetically mediated thermogenesis, as reflected by RMR, results in normalization of obesity-related hypertension. In contrast, insulin does not seem to play a major role in the pathogenesis of hypertension associated with obesity. Increased leptin levels in conjunction with decreased NO production in the presence of enhanced sympathetic activity may contribute to blood pressure elevation in the obese.


Thermoelectric power of bismuth nanocomposites.
Because of the increase in the electronic density of states in low-dimensional systems, semiconductor quantum wires constitute a most promising thermoelectric material. We report here the first experimental observation of a very large enhancement of the thermoelectric power of composites containing bismuth nanowires with diameters of 9 and 15 nm, embedded in porous alumina and porous silica. The temperature dependence of the electrical resistance shows that the samples are semiconductors with energy gaps between 0.17 and 0.4 eV, consistent with the theoretical predictions.


Chelating agent free-solid phase extraction (CAF-SPE) of Co(II), Cu(II) and Cd(II) by new nano hybrid material (ZrO2/B2O3).
New nano hybrid material (ZrO(2)/B(2)O(3)) was synthesized and applied as a sorbent for the separation and/or preconcentration of Co(II), Cu(II) and Cd(II) in water and tea leaves prior to their determination by flame atomic absorption spectrometry. Synthesized nano material was characterized by scanning electron microscope, transmission electron microscope and X-ray diffraction. The optimum conditions for the quantitative recovery of the analytes, including pH, eluent type and volume, flow rate of sample solution were examined. The effect of interfering ions was also investigated. Under the optimum conditions, adsorption isotherms and adsorption capacities have been examined. The recoveries of Co(II), Cu(II) and Cd(II) were 96 ± 3%, 95 ± 3%, 98 ± 4% at 95% confidence level, respectively. The analytical detection limits for Co(II), Cu(II), and Cd(II) were 3.8, 3.3, and 3.1 μg L(-1), respectively. The reusability and adsorption capacities (32.2 mg g(-1) for Co, 46.5 mg g(-1) for Cu and 109.9 mg g(-1) for Cd) of the sorbent were found as satisfactory. The accuracy of the method was confirmed by analyzing certified reference material (GBW-07605 Tea leaves) and spiked real samples. The method was applied for the determination of analytes in tap water and tea leaves.


Diagnosis and treatment of Wilson's disease.
Wilson's disease (WD) has moved on from being a recognized syndrome that was uniformly fatal to a curative disease for which the genetic basis has been discovered. Most pediatric patients present with hepatic manifestations, but some may have neurologic or psychiatric features. Clinical and biochemical screening, including liver biopsy for hepatic copper analysis, remain the standard for diagnosis, but haplotype analysis for siblings is now available and should be considered for family screening when possible. Lifelong medical therapy remains the mainstay of treatment, but treatment preferences are changing from penicillamine to alternative agents such as trientine and zinc. OLT remains lifesaving for those with fulminant WD and those in whom initial medical therapy fails. The future will probably see the application of rapid and accurate molecular diagnostic testing for this disorder and new therapeutic modalities such as hepatocyte transplantation, gene replacement therapy, and gene modification.


Interactive influences of neighborhood and individual socioeconomic status on alcohol consumption and problems.
To assess cross-level interactions between neighborhood and individual socioeconomic status (SES) on alcohol consumption and problems, and investigate three possible explanations for such interactions, including the double jeopardy, status inconsistency and relative deprivation hypotheses. Data from the 2000 and 2005 US National Alcohol Surveys were linked to the 2000 US Census to define respondent census tracts as disadvantaged, middle-class and advantaged. Risk drinking (consumption exceeding national guidelines), monthly drunkenness and alcohol problems were examined among low-, middle- and high-SES past-year drinkers (n = 8728). Gender-stratified, multiple logistic regression models were employed, and for outcomes with a significant omnibus F-test, linear contrasts were used to interpret interactions. Cross-level SES interactions observed for men indicated that residence in advantaged neighborhoods was associated with markedly elevated odds of risk drinking and drunkenness for low-SES men. Linear contrasts further revealed a nearly 5-fold increased risk for alcohol problems among these men, relative to middle-SES and high-SES men also living in advantaged neighborhoods. Among women, neighborhood disadvantage was related to increased risk for alcohol problems, but there were no significant SES interactions. These findings did not support theories of double jeopardy and status inconsistency. Consistent with the relative deprivation hypothesis, findings highlight alcohol-related health risks among low-SES men living in affluent neighborhoods. Future research should assess whether this pattern extends to other health risk behaviors, investigate causal mechanisms and consider how gender may influence these.


Gross and microscopic findings in the human esophagus after esophageal variceal band ligation: a postmortem analysis.
Endoscopic sclerotherapy has been the therapy of choice for controlling acute variceal hemorrhage. Recently, endoscopic band ligation has been utilized for the management of esophageal varices with fewer complications and greater efficacy. We report the pathologic findings in the human esophagus 5 days after esophageal variceal band ligation.


Arbuscular Mycorrhizal Symbiosis Alleviates Salt Stress in Black Locust through Improved Photosynthesis, Water Status, and K+/Na+ Homeostasis.
Soil salinization and the associated land degradation are major and growing ecological problems. Excess salt in soil impedes plant photosynthetic processes and root uptake of water and nutrients such as K+. Arbuscular mycorrhizal (AM) fungi can mitigate salt stress in host plants. Although, numerous studies demonstrate that photosynthesis and water status are improved by mycorrhizae, the molecular mechanisms involved have received little research attention. In the present study, we analyzed the effects of AM symbiosis and salt stress on photosynthesis, water status, concentrations of Na+ and K+, and the expression of several genes associated with photosynthesis (RppsbA, RppsbD, RprbcL, and RprbcS) and genes coding for aquaporins or membrane transport proteins involved in K+ and/or Na+ uptake, translocation, or compartmentalization homeostasis (RpSOS1, RpHKT1, RpNHX1, and RpSKOR) in black locust. The results showed that salinity reduced the net photosynthetic rate, stomatal conductance, and relative water content in both non-mycorrhizal (NM) and AM plants; the reductions of these three parameters were less in AM plants compared with NM plants. Under saline conditions, AM fungi significantly improved the net photosynthetic rate, quantum efficiency of photosystem II photochemistry, and K+ content in plants, but evidently reduced the Na+ content. AM plants also displayed a significant increase in the relative water content and an evident decrease in the shoot/root ratio of Na+ in the presence of 200 mM NaCl compared with NM plants. Additionally, mycorrhizal colonization upregulated the expression of three chloroplast genes (RppsbA, RppsbD, and RprbcL) in leaves, and three genes (RpSOS1, RpHKT1, and RpSKOR) encoding membrane transport proteins involved in K+/Na+ homeostasis in roots. Expression of several aquaporin genes was regulated by AM symbiosis in both leaves and roots depending on soil salinity. This study suggests that the beneficial effects of AM symbiosis on the photosynthetic capacity, water status, and K+/Na+ homeostasis lead to the improved growth performance and salt tolerance of black locust exposed to salt stress.


Pulmonary hypertension in systemic lupus erythematosus: relationship with antiphospholipid antibodies and severe disease outcome.
Pulmonary hypertension (PH) in systemic lupus erythematosus (SLE) is associated with an unfavorable prognosis. We investigated the characteristics of SLE patients with PH. The patients with a pulmonary artery systolic pressure more than 30 mmHg at rest on echocardiogram were diagnosed with PH. Echocardiography was done only in patients with clinical or radiological evidence suggesting PH. Right heart catheterization was not performed. We identified 10 SLE patients with PH between 1980 and 2000. We compared their clinical and laboratory parameters with those of 97 consecutive SLE patients without PH. Nine of the ten patients with PH were females. The mean age at the time of SLE onset was 25.2 ± 6.9 years; the mean duration of follow-up was 93.4 ± 52.8 months, and the interval between the onset of SLE and PH diagnosis was 9.0 ± 4.6 (5-21) years. Antiphospholipid antibody positivity was significantly higher in the PH group (80 vs. 36%; p < 0.05), but there was no significant difference between two groups in regard to secondary antiphospholipid syndrome. The frequency of Raynaud's phenomenon was higher in PH group (60 vs. 27%; p < 0.05). Renal involvement (80 vs. 43%; p < 0.05), neuropsychiatric involvement (40 vs. 7.2%; p < 0.005) and serositis (70 vs. 14.4%; p < 0.001) were significantly more frequent in the PH group. The mean damage score in patients with and without PH were 4.0 ± 2.4 and 0.4 ± 1.0, respectively (p < 0.001). Four patients with PH died during the follow-up. This study reveals that the presence of PH defines a subgroup of patients with a severe disease and increased mortality. Antiphospholipid antibodies and Raynaud's phenomenon may contribute to the pathogenesis of PH. We recommend that all patients with SLE, especially those positive for antiphospholipid antibodies and/or with signs of Raynaud's phenomenon should be regularly evaluated for the development of PH.


Conformational Changes of Bovine Serum Albumin Induced by Adsorption on Different Clay Surfaces: FTIR Analysis.
Interactions between proteins and clays perturb biological activity in ecosystems, particularly soil extracellular enzyme activity. The pH dependence of hydrophobic, hydrophilic, and electrostatic interactions on the adsorption of bovine serum albumin (BSA) is studied. BSA secondary structures and hydration are revealed from computation of the Amide I and II FTIR absorption profiles. The influence of ionization of Asp, Glu, and His side chains on the adsorption processes is deduced from correlation between p(2)H dependent carboxylic/carboxylate ratio and Amide band profiles. We quantify p(2)H dependent internal and external structural unfolding for BSA adsorbed on montmorillonite, which is an electronegative phyllosilicate. Adsorption on talc, a hydrophobic surface, is less denaturing. The results emphasize the importance of electrostatic interactions in both adsorption processes. In the first case, charged side chains directly influence BSA adsorption that generate the structural transition. In the second case, the forces that attract hydrophobic side chains toward the protein-clay interface are large enough to distort peripheral amphiphilic helical domains. The resulting local unfolding displaces enough internal ionized side chains to prevent them from establishing salt bridges as for BSA native structure in solution. On montmorillonite, a particular feature is a higher protonation of the Asp and Glu side chains of the adsorbed BSA than in solution, which decreases coulombic repulsion. Copyright 2000 Academic Press.


OH-initiated degradation of unsaturated esters in the atmosphere: kinetics in the temperature range of 287-313 K.
The kinetics of the gas-phase reactions of hydroxyl radicals (OH) with methyl methacrylate (k(1)), butyl methacrylate (k(2)), butyl acrylate (k(3)), and vinyl acetate (k(4)) have been investigated for the first time as a function of temperature using the relative technique. The experiments were performed in a 1080 L quartz glass photoreactor over the temperature range (T = 287-313 K) at a total pressure of 760 +/- 10 Torr synthetic air using in situ FTIR absorption spectroscopy to monitor the concentration-time behaviors of reactants. OH radicals were produced by the 254 nm photolysis of hydrogen peroxide (H(2)O(2)). The following Arrhenius expressions (in units of cm(3) molecule(-1) s(-1)) adequately describe the measured rate coefficients as a function of temperature: k(1) = (1.97 +/- 0.95) x 10(-12) exp[(921 +/- 52)/T], k(2) = (1.65 +/- 1.05) x 10(-11) exp[(413 +/- 34)/T], k(3) = (4.4 +/- 2.5) x 10(-13) exp[(1117 +/- 105)/T], and k(4) = (4.06 +/- 2.02) x 10(-12) exp[(540 +/- 49)/T]. All of the rate coefficients display a negative temperature dependence and low pre-exponential factor, which supports an addition mechanism for the reactions involving reversible OH-adduct formation. The rate coefficients (in units of cm(3) molecule(-1) s(-1)) determined at room temperature (298 K) were as follows: k(1) = (4.30 +/- 0.98) x 10(-11), k(2) = (6.63 +/- 1.42) x 10(-11), k(3) = (2.17 +/- 0.48) x 10(-11), and k(4) = (2.48 +/- 0.61) x 10(-11). The results are compared with previous values of the rate coefficients reported in the literature, which were mainly measured at room temperature. The reactivity of the various unsaturated esters toward the OH radical is discussed in terms of structure activity relationships and parallels are drawn with the OH-radical activities of structurally similar compounds. Using the kinetic parameters determined in this work, residence times of the esters in the atmosphere with respect to their reaction with OH have been determined and are compared with other possible degradation pathways. Possible atmospheric implications of the various degradation pathways studied are discussed.


Computational capacity of the universe.
All physical systems register and process information. The laws of physics determine the amount of information that a physical system can register (number of bits) and the number of elementary logic operations that a system can perform (number of ops). The Universe is a physical system. The amount of information that the Universe can register and the number of elementary operations that it can have performed over its history are calculated. The Universe can have performed 10(120) ops on 10(90) bits ( 10(120) bits including gravitational degrees of freedom).


Clinical assessment of adenoidal obstruction based on the nasal obstruction index is no longer useful in children.
To evaluate the accuracy of clinical assessment of adenoidal obstruction based on a standardized score of the degree of mouth breathing and speech hyponasality (nasal obstruction index [NOI]) in comparison to nasal fiberoptic endoscopy. Cross-sectional study with planned data collection. Outpatient clinics of the Departments of Maternal and Pediatric Sciences and Specialized Surgical Sciences, University of Milan, Italy. Children aged three to 12 years with adenoidal obstruction suspected on the grounds of persistent/recurrent otitis media or perceived obstructive nasal breathing were eligible. Ear, nose, and throat examination, allergy testing, NOI measurement, and nasal fiberoptic endoscopy to assess the degree of adenoidal hypertrophy were performed. Agreement between the NOI and adenoidal hypertrophy grade was assessed in the patients as a whole and by clinical subgroups. A total of 202 children were enrolled: 54.9 percent had otological diseases and 45.1 percent had perceived obstructive nasal breathing. Most of the children (79.2%) showed mild or moderate clinical nasal obstruction. Adenoidal hypertrophy ranged from no obstruction (18%) to severe obstruction (38%). There was no substantial agreement between the NOI and the degree of adenoidal obstruction in the population as a whole and in all the clinical subgroups. False positive findings were significantly more frequent among allergic children (50%) than non-allergic children (22.4%, P = 0.009). Clinical assessment based on the NOI is incapable of accurately predicting the degree of adenoidal obstruction. In children with clinical nasal obstruction not explainable by adenoidal size, the clinician should consider, among causes of more anterior obstruction, nasal allergy.