Molecular and cellular mechanisms of receptor-mediated endocytosis.
In general, receptors are involved in pathways of endocytosis, either constitutive or ligand induced. These receptors cluster in clathrin-coated pits, enter the cell via clathrin-coated vesicles, pass through an acidified endosome in which the receptors and ligands are sorted, and then either recycle to the cell surface, become stored intracellularly, or are degraded in lysosomes. The internalization pathways serve a variety of functions, such as nutrient uptake, removal of activated proteins, clearance of macromolecules, opportunistic entry of certain viruses and toxins, dissociation and degradation of ligand, and receptor-level regulation. Many receptors follow more than one intracellular pathway, depending on the cell type, receptor concentration, type of ligand, ligand valency, and ligand concentration. Although endocytosis is common to all nucleated eukaryotic cells, the factors that regulate these receptor-mediated endocytic pathways are not fully understood. Defective receptors that are not capable of undergoing normal endocytosis can lead to certain disease states, as in the case of familial hypercholesteremia (FH). This review has three objectives: (i) to describe the different routes that receptors and ligands follow after internaliation; (ii) to describe the potential mechanisms which regulate the initiation and subsequent sorting of receptors and ligands so they reach their final destination; and (iii) to describe the potential functions of receptor-mediated endocytosis.


Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes.
Type 2 diabetes is frequently associated with an inflammatory status; the relationships between low-grade inflammation and diabetic nephropathy are still unclear. The aim of this study was to evaluate the relationships between acute-phase markers of inflammation, glomerular structure, and albumin excretion rate (AER) in type 2 diabetes. In 74 patients with type 2 diabetes (23 normoalbuminuric, 30 microalbuminuric, and 21 proteinuric) fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP), and IL-6 were determined. AER was measured on three 24-h urine collections; GFR was measured by 51Cr EDTA plasma clearance. A kidney biopsy was performed, and mesangial fractional volume [Vv(mes/glom)] and glomerular basement membrane (GBM) width were estimated by electron microscopic morphometric analysis. CRP, fibrinogen, SAA, and IL-6 differed among groups, with proteinuric patients having the highest levels. SAA and fibrinogen correlated with AER (P < 0.03 and P < 0.001, respectively). GBM width and Vv(mes/glom) increased from normoalbuminuric to proteinuric patients [P < 0.005 normoalbuminuric and microalbuminuric versus proteinuric for GBM, P < 0.01 normoalbuminuric versus proteinuric for Vv(mes/glom)]. In patients with increased GBM width (> 396 nm), CRP, SAA, and IL-6 were higher than in patients with normal GBM width (P < 0.003, P < 0.004, and P < 0.0004, respectively). GBM width was directly correlated with fibrinogen (r = 0.33, P < 0.002) and IL-6 (r = 0.25 P < 0.05). In conclusion, this study demonstrates that acute-phase markers of inflammation are associated with nephropathy status and GBM thickening, suggesting a role for inflammation in the pathogenesis of diabetic glomerulopathy.


The Oxidative Stress and Nervous Distress Connection in Gastrointestinal Disorders.
Oxidative stress is increasingly recognized as a central player in a range of gastrointestinal (GI) disorders, as well as complications stemming from therapeutic interventions. This article presents an overview of the mechanisms of oxidative stress in GI conditions and highlights a link between oxidative insult and disruption to the enteric nervous system (ENS), which controls GI functions. The dysfunction of the ENS is characteristic of a spectrum of disorders, including neurointestinal diseases and conditions such as inflammatory bowel disease (IBD), diabetic gastroparesis, and chemotherapy-induced GI side effects. Neurons in the ENS, while essential for normal gut function, appear particularly vulnerable to oxidative damage. Mechanistically, oxidative stress in enteric neurons can result from intrinsic nitrosative injury, mitochondrial dysfunction, or inflammation-related pathways. Although antioxidant-based therapies have shown limited efficacy, recognizing the multifaceted role of oxidative stress in GI diseases offers a promising avenue for future interventions. This comprehensive review summarizes the literature to date implicating oxidative stress as a critical player in the pathophysiology of GI disorders, with a focus on its role in ENS injury and dysfunction, and highlights opportunities for the development of targeted therapeutics for these diseases.


Active learning with support vector machine applied to gene expression data for cancer classification.
There is growing interest in the application of machine learning techniques in bioinformatics. The supervised machine learning approach has been widely applied to bioinformatics and gained a lot of success in this research area. With this learning approach researchers first develop a large training set, which is a time-consuming and costly process. Moreover, the proportion of the positive examples and negative examples in the training set may not represent the real-world data distribution, which causes concept drift. Active learning avoids these problems. Unlike most conventional learning methods where the training set used to derive the model remains static, the classifier can actively choose the training data and the size of training set increases. We introduced an algorithm for performing active learning with support vector machine and applied the algorithm to gene expression profiles of colon cancer, lung cancer, and prostate cancer samples. We compared the classification performance of active learning with that of passive learning. The results showed that employing the active learning method can achieve high accuracy and significantly reduce the need for labeled training instances. For lung cancer classification, to achieve 96% of the total positives, only 31 labeled examples were needed in active learning whereas in passive learning 174 labeled examples were required. That meant over 82% reduction was realized by active learning. In active learning the areas under the receiver operating characteristic (ROC) curves were over 0.81, while in passive learning the areas under the ROC curves were below 0.50.


Airway Inflammation Before and After Bronchial Thermoplasty in Severe Asthma.
Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma, of which the working mechanism and responder profile are partly unknown. The aim of this study is to analyse whether BT alters airway inflammation by epithelial gene expression, inflammatory cell counts and cytokines, and whether this relates to treatment response. In this clinical trial, 28 severe asthma patients underwent bronchoscopy before and after treatment to obtain bronchial brushes and bronchoalveolar lavage fluid (BALF) from treated and untreated airways. RNA was extracted from bronchial brushes for transcriptome analysis, and BALF cells and cytokines were analysed. Asthma quality of life questionnaires were used to distinguish responders from non-responders. We compared results before and after treatment, between treated and untreated airways, and between responders and non-responders. Gene expression of airway epithelium related to airway inflammation gene set was significantly downregulated in treated airways compared to untreated airways, although this did not differ for patients before and after treatment. No differences were observed in cell counts and cytokines, neither from the untreated compared to treated airways, nor before and after treatment. At baseline, compared to non-responders, the expression of genes related to glycolysis in bronchial epithelium was downregulated and both BALF and blood eosinophil counts were higher in responders. Local differences in gene sets pertaining to epithelial inflammatory status were identified between treated and untreated airways after treatment, not resulting in changes in differential cell counts and cytokine analyses in BALF. Secondly, baseline epithelial glycolysis genes and eosinophil counts in BALF and blood were different between responders and non-responders. The observations from this study demonstrate the potential impact of BT on epithelial gene expression related to airway inflammation while also identifying a possible responder profile.


Review: corneal endothelial cell derivation methods from ES/iPS cells.
Globally, approximately 12.7 million people are awaiting a transplantation, while only 185,000 cases of corneal transplantation are performed in a year. Corneal endothelial dysfunction (bullous keratopathy) due to Fuchs' corneal endothelial dystrophy, or insults associated with intraocular surgeries, shared half of all indications for corneal transplantation. Regenerative therapy for corneal endothelium independent of eye bank eyes has great importance to solve the large supply-demand mismatching in corneal transplantation and reduce the number of worldwide corneal blindness. If corneal endothelial cells could be derived from ES or iPS cells, these stem cells would be the ideal cell source for cell therapy treatment of bullous keratopathy. Four representative corneal endothelial cell derivation methods were reviewed. Components in earlier methods included lens epithelial cell-conditioned medium or fetal bovine serum, but the methods have been improved and materials have been chemically more defined over the years. Conditioned medium or serum is replaced to recombinant proteins and small molecule compounds. These improvements enabled to open the corneal endothelial developmental mechanisms, in which epithelial-mesenchymal and mesenchymal-endothelial transition by TGF beta, BMP, and Wnt signaling have important roles. The protocols are gradually approaching clinical application; however, proof of efficacy and safety of the cells by adequate animal models are the challenges for the future.


Recent advances in mucous membrane pemphigoid.
The aim of this article is to review articles on mucous membrane pemphigoid published in the English literature from 2006 to 2007. The risk of ocular disease among patients with oral only mucous membrane pemphigoid is estimated at 15-20% at 5 years. Biopsy with direct immunofluorescent testing is essential to confirm the diagnosis because histopathology even with electron microscopy does not appear to be specific enough to confirm the diagnosis of mucous membrane pemphigoid with consistency. Autoantibodies to IgG and IgG4 appear to be the most common findings observed on direct immunofluorescent testing in patients with mucous membrane pemphigoid. Treatment for mucous membrane pemphigoid typically involves immunosuppressive drugs, including biologic therapy, as well as intravenous immunoglobulin, although results have been mixed and the majority of data reported still are from case series and anecdotal evidence. Mucous membrane pemphigoid continues to be a potentially life and sight threatening disease. Therapy for this disease continues to show varied results although benefits are clearly seen in some patients. The immunosuppressive drugs used for treating mucous membrane pemphigoid and certain definitive categories of mucous membrane pemphigoid continue to evolve.


Use of intermediate cardiovascular endpoints in intervention studies: not as easy as it seems?
In the current issue of the Journal, Van den Berkmortel and coworkers' report on the effect of smoking cessation on cardiovascular risk reduction, as estimated by assessment of progression of carotid intima-media thickness (CIMT) and arterial stiffness. Much to the authors' surprise, their nonrandomised study among 33 subjects who stopped smoking for at least two years, 55 persistent smokers and 50 never-smokers showed no difference in rate of change in CIMT or arterial stiffness across the groups after two years of intervention. The intriguing question of the paper is whether the finding is true or may be attributed to potential flaws of the study, focussing on design and analytical procedures, the choice of the endpoint and the power of the study.


Transcriptional oncogenomic hot spots in Barrett's adenocarcinomas: serial analysis of gene expression.
Serial analysis of gene expression (SAGE) provides quantitative and comprehensive expression profiling in a given cell population. In our efforts to define gene expression alterations in Barrett's-related adenocarcinomas (BA), we produced eight SAGE libraries and obtained a total of 457,894 expressed tags with 32,035 (6.9%) accounting for singleton tags. The tumor samples produced an average of 71,804 tags per library, whereas normal samples produced an average of 42,669 tags per library. Our libraries contained 67,200 unique tags representing 16,040 known gene symbols. Five hundred and sixty-eight unique tags were differentially expressed between BAs and normal tissue samples (at least twofold; P<or=0.05), 395 of these matched to known genes. Interestingly, the distribution of altered genes was not uniform across the human genome. Overexpressed genes tended to cluster in well-defined hot spots located in certain chromosomes. For example, chromosome 19 had 26 overexpressed genes, of which 18 mapped to 19q13. Using the gene ontology approach for functional classification of genes, we identified several groups that are relevant to carcinogenesis. We validated the SAGE results of five representative genes (ANPEP, ECGF1, PP1201, EIF5A1, and GKN1) using quantitative real-time reverse-transcription PCR on 31 BA samples and 26 normal samples. In addition, we performed an immunohistochemistry analysis for ANPEP, which demonstrated overexpression of ANPEP in 6/7 (86%) Barrett's dysplasias and 35/65 (54%) BAs. ANPEP is a secreted protein that may have diagnostic and/or prognostic significance for Barrett's progression. The use of genomic approaches in this study provided useful information about the molecular pathobiology of BAs.


Ca++/calmodulin-regulated protein phosphorylation in the Aplysia nervous system.
Protein substrates for an endogenous CA++/calmodulin-dependent protein kinase were characterized in the Aplysia nervous system. Ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-washed membrane fractions from Aplysia ganglia contain an endogenous Ca++/calmodulin-dependent protein kinase which phosphorylates a number of membrane proteins. Such washed membrane preparations exhibit little or no adenosine 3':5'-cyclic phosphate (cAMP)-dependent protein kinase activity but do contain substrates for exogenously added catalytic subunit of cAMP-dependent protein kinase. Low concentrations of catalytic subunit rapidly stimulate the phosphorylation of a protein of Mr 70,000 and of a 52,000-dalton doublet, indicating that these proteins are major substrates for this enzyme. Phosphopeptide patterns obtained after limited proteolysis suggest that the 70,000-dalton protein and the 52,000-dalton doublet are similar in structure and that their phosphorylation is stimulated both by Ca++/calmodulin and by catalytic subunit. The 52,000-dalton doublet consists of two closely spaced bands: the phosphorylation of the upper band is stimulated by catalytic subunit, whereas the phosphorylation of the lower band is stimulated by the endogenous Ca++/calmodulin-dependent protein kinase. The results suggest that in Aplysia membranes a number of proteins can be phosphorylated by both Ca++/calmodulin-dependent protein kinase and catalytic subunit of cAMP-dependent protein kinase. This convergence of biochemical effects of Ca++ and cAMP may play a role in some of their physiological actions in molluscan neurons.


[All physicians--not only physicians in charge need leadership training].
Management education programmes for physicians range from university courses to courses offered by private companies. Some hospitals and regions arrange local management education for physicians in specialist training and certified specialists, but mostly for staff in executive positions. Only 245 places are available on the one-week courses for physicians in specialist training during the whole of year 2000 in Sweden; 637 applications were received for the spring courses only. There are 5,000 physicians in specialist training in Sweden. There is a great need for increased investments in the fields of education in administration, economy, leadership and management for physicians.


Generation of intestinal mucosal lymphocytes in SCID mice reconstituted with mature, thymus-derived T cells.
Transfer of peripheral lymph node lymphocytes to SCID mice leads to the long term establishment of mucosal T lymphocytes within the epithelium and lamina propria of the small and large intestines. Analysis of engrafted intraepithelial lymphocytes (IEL) showed that they had acquired a surface phenotype that in several respects is typical of IEL. In addition, the functional profile of engrafted IEL derived from lymph node T cells was similar to that of normal IEL; as the donor-derived T cells exhibited a strong cytolytic activity, a poor proliferative response to mitogenic stimuli, and a tendency to home and expand specifically in the intestine upon transfer to secondary SCID recipients. Optimal engraftment of intestinal T cells required bacterial flora, as the number of lymphocytes was greatly reduced in SCID recipients with a reduced flora. These results demonstrate that mature, thymus-derived T cells can migrate to the intestine and become functionally specialized to the intestinal milieu. The acquisition of phenotypic markers characteristic of the intestinal microenvironment by engrafted cells suggests that T cell migration of lymphocytes to the SCID intestine is not aberrant, but it may reflect processes that are ongoing in immunocompetent mice. Furthermore, these data suggest that the homing and/or expansion of typical, thymus-derived T cells in the intestine may be driven by luminal Ags such as those derived from bacterial flora.


Time series analysis-based seasonal autoregressive fractionally integrated moving average to estimate hepatitis B and C epidemics in China.
Hepatitis B (HB) and hepatitis C (HC) place the largest burden in China, and a goal of eliminating them as a major public health threat by 2030 has been set. Making more informed and accurate forecasts of their spread is essential for developing effective strategies, heightening the requirement for early warning to deal with such a major public health threat. To monitor HB and HC epidemics by the design of a paradigmatic seasonal autoregressive fractionally integrated moving average (SARFIMA) for projections into 2030, and to compare the effectiveness with the seasonal autoregressive integrated moving average (SARIMA). Monthly HB and HC incidence cases in China were obtained from January 2004 to June 2023. Descriptive analysis and the Hodrick-Prescott method were employed to identify trends and seasonality. Two periods (from January 2004 to June 2022 and from January 2004 to December 2015, respectively) were used as the training sets to develop both models, while the remaining periods served as the test sets to evaluate the forecasting accuracy. There were incidents of 23400874 HB cases and 3590867 HC cases from January 2004 to June 2023. Overall, HB remained steady [average annual percentage change (AAPC) = 0.44, 95% confidence interval (95%CI): -0.94-1.84] while HC was increasing (AAPC = 8.91, 95%CI: 6.98-10.88), and both had a peak in March and a trough in February. In the 12-step-ahead HB forecast, the mean absolute deviation (15211.94), root mean square error (18762.94), mean absolute percentage error (0.17), mean error rate (0.15), and root mean square percentage error (0.25) under the best SARFIMA (3, 0, 0) (0, 0.449, 2)12 were smaller than those under the best SARIMA (3, 0, 0) (0, 1, 2)12 (16867.71, 20775.12, 0.19, 0.17, and 0.27, respectively). Similar results were also observed for the 90-step-ahead HB, 12-step-ahead HC, and 90-step-ahead HC forecasts. The predicted HB incidents totaled 9865400 (95%CI: 7508093-12222709) cases and HC totaled 1659485 (95%CI: 856681-2462290) cases during 2023-2030. Under current interventions, China faces enormous challenges to eliminate HB and HC epidemics by 2030, and effective strategies must be reinforced. The integration of SARFIMA into public health for the management of HB and HC epidemics can potentially result in more informed and efficient interventions, surpassing the capabilities of SARIMA.


Mitochondrial DNA mutations in human colonic crypt stem cells.
The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell.


Systematic manipulations of the biological stress systems result in sex-specific compensatory stress responses and negative mood outcomes.
Women are twice as likely as men to be diagnosed with anxiety and mood disorders. One potential underlying mechanism is sex differences in physiological and psychological responses to stress; however, no studies to date have investigated this proposed mechanism experimentally. In a double-blind, placebo-controlled design, pharmacological challenges were administered to individually suppress the hypothalamic-pituitary-adrenal (HPA) axis, or the sympathetic nervous system (SNS) prior to stress exposure, to investigate sex differences in the resulting cross talk among the physiological and psychological stress responses. Sex-specific compensatory patterns and psychological effects emerged when the stress systems were manipulated. Men demonstrated heightened SNS reactivity to stress when the HPA axis was suppressed, and greater HPA reactivity after SNS suppression. This ability to react appropriately to the stressor, even with one system, did not lead to significant negative mood effects. In women, higher baseline activation (but dampened reactivity to stress) of SNS or HPA was observed when the other system was suppressed. This was coupled with worsened mood in response to stress when either stress system was compromised. Our results indicate that men and women may be differentially sensitive to fluctuations of their stress systems. This might be a potential link that underlies the sexual dimorphism in vulnerability for psychopathology.


Developmental biology of Argas neghmei Kohls & Hoogstraal (Acari: Argasidae) under laboratory conditions.
In order to describe the developmental biology of the tick Argas neghmei Kohls & Hoogstraal under laboratory conditions, 40 females and 40 males were collected from chicken coops located in Calama (II Region, Chile). They were fed on chickens and maintained under two laboratory conditions: one group at 30 +/- 5 degrees C and 35 +/- 5 % RH and another at 27 +/- 5 degrees C and 80 +/- 5 % RH, both at 12: 12 h L:D photoperiod. The ticks were observed daily to determine larval feeding periods, preoviposition, oviposition, egg incubation as well as the frequency of egg laying, number of eggs laid, and percentage of larval hatching. Females did not lay eggs at 80 +/- 5% RH, and data on the biology of this tick was obtained only at 35 +/- 5% RH. The life cycle of A. neghmei lasted an average of 269 days. Feeding period of each nymphal stage as well as of adult females between oviposition events lasted less than a day. Females laid on average 1.8 egg batches and egg-laying period lasted on average 14 days, during which about 96 eggs were laid per female.


The pharmacokinetics of oxycodone.
Oxycodone is among the most commonly used opioid analgesics for the relief of moderate-to-severe pain and is pharmacodynamically comparable to morphine. Oxycodone is available in the United States in oral dosage forms and controlled-release tablets. Studies have demonstrated marked interindividual variation in the pharmacokinetics of oxycodone. The pharmacokinetics of oral oxycodone differs from oral morphine in that it has a higher bioavailability, a slightly longer half-life, and is hepatically metabolized by cytochrome P450 rather than undergoing glucuronidation. Understanding oxycodone pharmacokinetics favors safe and effective use of this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and May 2004 relevant to the pharmacokinetics of oxycodone. These publications were reviewed and the literature summarized regarding unique and clinically important elements of oxycodone disposition including its absorption profile (immediate release, controlled release, rectal administration, and intranasal administration), distribution, and its metabolism/excretion. Special populations, including children and those with liver/renal failure, have a unique oxycodone pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.


Smart Indigenous Youth: The Smart Platform Policy Solution for Systems Integration to Address Indigenous Youth Mental Health.
Indigenous youth mental health is an urgent public health issue, which cannot be addressed with a one-size-fits-all approach. The success of health policies in Indigenous communities is dependent on bottom-up, culturally appropriate, and strengths-based prevention strategies. In order to maximize the effectiveness of these strategies, they need to be embedded in replicable and contextually relevant mechanisms such as school curricula across multiple communities. Moreover, to engage youth in the twenty-first century, especially in rural and remote areas, it is imperative to leverage ubiquitous mobile tools that empower Indigenous youth and facilitate novel Two-Eyed Seeing solutions. Smart Indigenous Youth is a 5-year community trial, which aims to improve Indigenous youth mental health by embedding a culturally appropriate digital health initiative into school curricula in rural and remote Indigenous communities in Canada. This policy analysis explores the benefits of such upstream initiatives. More importantly, this article describes evidence-based strategies to overcome barriers to implementation through the integration of citizen science and community-based participatory research action.


Competition and fixation of cohorts of adaptive mutations under Fisher geometrical model.
One of the simplest models of adaptation to a new environment is Fisher's Geometric Model (FGM), in which populations move on a multidimensional landscape defined by the traits under selection. The predictions of this model have been found to be consistent with current observations of patterns of fitness increase in experimentally evolved populations. Recent studies investigated the dynamics of allele frequency change along adaptation of microbes to simple laboratory conditions and unveiled a dramatic pattern of competition between cohorts of mutations, i.e., multiple mutations simultaneously segregating and ultimately reaching fixation. Here, using simulations, we study the dynamics of phenotypic and genetic change as asexual populations under clonal interference climb a Fisherian landscape, and ask about the conditions under which FGM can display the simultaneous increase and fixation of multiple mutations-mutation cohorts-along the adaptive walk. We find that FGM under clonal interference, and with varying levels of pleiotropy, can reproduce the experimentally observed competition between different cohorts of mutations, some of which have a high probability of fixation along the adaptive walk. Overall, our results show that the surprising dynamics of mutation cohorts recently observed during experimental adaptation of microbial populations can be expected under one of the oldest and simplest theoretical models of adaptation-FGM.


Interactions between large and small detritivores influence how biodiversity impacts litter decomposition.
Understanding how biodiversity loss influences plant litter decomposition-that is, the biologically mediated conversion of coarse to fine particulate organic matter-is crucial to predict changes in the functioning of many stream ecosystems, where detrital food webs are dominant. Rates of litter decomposition are influenced by detritivore diversity, but the mechanisms behind this relationship are uncertain. As differences in detritivore body size are a major determinant of interspecific interactions, they should be key for predicting effects of detritivore diversity on decomposition. To explore this question, we manipulated detritivore diversity and body size simultaneously in a microcosm experiment using two small (Leuctra geniculata and Lepidostoma hirtum) and two large detritivore species (Sericostoma pyrenaicum and Echinogammarus berilloni) in all possible 1-, 2- and 4-species combinations, and litter discs of Alnus glutinosa. We expected that larger species would facilitate smaller species through the production of smaller litter fragments, resulting in faster decomposition and greater growth of smaller species in polycultures containing species of different body size. To examine this hypothesis, we used a set of "diversity-interaction" models that explored how decomposition was affected by different interspecific interactions and the role of body size, and quantified the magnitude of such effect through ratios of decomposition rates and detritivore growth between polycultures and monocultures. We found a clear positive effect of detritivore diversity on decomposition, which was mainly explained by facilitation and niche partitioning. Facilitation of small animals by larger ones was evidenced by a 12% increase in decomposition rates in polycultures compared to monocultures and the higher growth (20%) of small species, which partly fed on fine particulate organic matter produced by larger animals. When the large species were together in polycultures, decomposition was enhanced by 19%, but there were no changes in growth; niche partitioning was a plausible mechanism behind the increase in decomposition rates, as both species fed on different parts of litter discs, only one species being able to eat less palatable parts. Our study demonstrates that interspecific differences in body size should be taken into account in diversity-decomposition studies. Future studies should also consider differences in species' vulnerability to extinction depending on body size and how this might affect ecosystem functioning in different scenarios of detritivore diversity and more complex food webs.


[Itraconazole and secnidazole capsules vs. vaginal ovules of fluocinolone acetonide, nystatin and metronidazole in the symptomatic treatment of vaginitis].
Evaluation of oral treatment in vaginitis and vaginosis using Itraconazol and sechidazol, in comparison to topic treatment using vaginal ovules of acetonido of fluocinolona 0.50 mg, nistatina 100,000 U and metronidazol 500 mg. Longitudinal, prospective and open comparative study. Servicio de Reproducción Humana(Human Reproduction Department), Centro Médico Nacional "20 de Noviembre". Forty female patients, without any relevant differences in their general characteristics, chose diagnosis was vaginitis and vaginosis, who were medically treated through external consultation, divided in two groups of twenty each one. Group 1 oral treatment with itraconazol and secnidazol. Group 2 had topic treatment with fluocinolona, nistatina and metronidazol. All of the patients were controlled in seven and fourteen days time, in order to evaluate the intensity of their clinical symptomatology, as well as the efficacy in both ways of treatment. Leukorrhea was the most important symptom in all the cases, going from minor to serious white discharge. After the treatment, we found a relevant difference statistically significative in patients treated with intraconazol and secnidazol. We did not find any differences in relation to ardor, pruritus, dispareunia and disuria at post-treatment evaluation. However, group 1 betterment was statistically significative between the first and the seventh days of treatment. Treating vaginitis or vaginosis (or both) with itraconazol and secnidazol takes less time for betterment in addition to comfort and easiness of oral administration; therefore, we consider them proper medicines in these specific cases.


Biochemical and morphological changes in hepatic nuclear membranes produced by N-hydroxy-2-acetylaminofluorene.
The effect of N-hydroxy-2-acetylaminofluorene on the ultrastructure and synthesis of hepatic neclear membranes was evaluated in partially hepatectomized rats. The incorporation of L-[4,5-3H]leucine into two nuclear membrane fractions increased within 2 hr after hepatic resection and reached a peak at 20 hr. After partial hepatectomy, the decay of radioactivity in nuclear membrane proteins labeled with L-[4,5-3H]leucine revealed similar half-lives for the two membrane fractions when compared to those obtained from sham-operated animals. The protein concentration of the nuclear membrane fraction of higher density decreased sharply within 2 hr after partial hepatectomy and remained low throughout a 20-hr postoperative period. Polyacrylamide gel electrophoresis of both nuclear membrane fractions showed a similar composition. Nine proteins were resolved, varying from 21,000 to 190,000 daltons. The two major protein bands were in the range of 50,000 and 70,000 daltons, respectively. Treatment of partially hepatectomized animals with N-hydroxy-2-acetylaminofluorene showed marked dilation of the nuclear envelope and rough endoplasmic reticulum in situ upon electron microscopic examination. Vacuolization and evagination of the perinuclear membranes were also noticeable in isolated nuclei obtained from carcinogen-treated rats. Inhibition by N-hydroxy-2-acetylaminofluorene of the incorporation of L-[4,5-3H]leucine into the nuclear membranes was dose-dependent and remained depressed throughout a 60-min labeling period. These results suggest that the inhibitory effects on RNA and protein synthesis previously shown to be produced by this arylhydroxylamine hepatocarcinogen may lead to disruption of the morphology and synthesis of the nuclear envelope.


Experiences of Young Parents with Perinatally Acquired HIV.
This research explores the perceptions of adolescents and young adults (AYA) living with perinatally acquired HIV (PHIV) as they transition into parenthood. We conducted hour-long, semistructured audio-recorded interviews with a purposive sample of 17 AYA parents with PHIV who were current or former patients at two US pediatric/adolescent infectious diseases clinics. Participants were asked about challenges/rewards of parenting and anticipated future fertility desires/intentions. Analysis of the transcribed interviews was guided by grounded theory. Mean age of participants was 22 years. The majority were African American (n = 8) or Hispanic (n = 6) and female (n = 14). Two participants were pregnant and others had a range of 1-3 children (mean = 1.4), one of whom was HIV positive. Analyses revealed that time with their child was a valuable commodity. Participants expressed concerns about not "being there" for their child due to sickness and worries that their child may experience HIV-related discrimination once a parent's HIV status was disclosed. The importance of being a role model and present in their child's life over time was emphasized and served as motivation to pursue education and employment opportunities. Those parents who intended to have another child were motivated by a strong desire to create a legacy and a family of their own as a way to deal with HIV-related losses and stigma. Participants reported the importance of emotional support offered by providers, as well as concrete social services available in that care setting even if they had transitioned to adult care. AYA also expressed parenting rewards/challenges similar to those of their uninfected peers. As youth with PHIV continue to mature, increasing numbers will become parents. It is incumbent upon both pediatric and adult providers to support newly formed families living in the context of intergenerational HIV infection.


Risk of thromboembolic events in controlled trials of rFVIIa in spontaneous intracerebral hemorrhage.
Recombinant activated factor VII (rFVIIa) reduces hematoma expansion and improves outcome after intracerebral hemorrhage (ICH), with an apparent increase in nonfatal thromboembolic events (TEs) with higher doses. Despite low incidences of such events in rFVIIa-treated hemophiliacs, the frequency in older patients with more atherosclerosis and immobility has yet to be defined. Data were pooled from 3 randomized placebo-controlled studies in patients diagnosed within 3 hours of spontaneous ICH who received a single dose of rFVIIa (5 to 160 microg/kg; n=371) or placebo (n=115). Clinical/laboratory evaluations, lower extremity Doppler studies, and 72-hour CT scans were used to monitor for TEs. Adverse events occurring while hospitalized and serious events occurring through day 90 were carefully reviewed. There was no overall increase in risk of total TEs in rFVIIa-treated patents; however, there were more arterial, but not venous, TEs in the high dose group (120 to 160 microg/kg) compared with placebo (5.4% versus 1.7%; P=0.13). Arterial events occurring within 7 days of drug administration classified as possibly or probably associated with study drug included myocardial ischemia (n=9, 8 were non-ST-segment elevation and non-Q-wave events; 2 of the 9 had sequelae) and ischemic stroke (n=9, 4 of which had likely causes other than rFVIIa). Regression analysis identified high doses (120 to 160 microg/kg) of rFVIIa as the only factor associated with arterial TEs (odds ratio=6.75; P=0.02). There appears to be a increased risk of arterial TEs associated with higher doses of rFVIIa in ICH patients as compared with placebo. Further studies are underway to identify specific factors associated with these events and to define the dose that maximizes benefit and minimizes risk.


Adapting the transtheoretical model of change to the bereavement process.
Theorists currently believe that bereaved people undergo some transformation of self rather than returning to their original state. To advance our understanding of this process, this article presents an adaptation of Prochaska and DiClemente's transtheoretical model of change as it could be applied to the journey that bereaved individuals experience. This theory is unique because it addresses attitudes, intentions, and behavioral processes at each stage; it allows for a focus on a broader range of emotions than just anger and depression; it allows for the recognition of two periods of regression during the bereavement process; and it adds a maintenance stage, which other theories lack. This theory can benefit bereaved individuals directly and through the increased awareness among counselors, family, friends, employers, and society at large. This theory may also be used as a tool for bereavement programs to consider whether they are meeting clients' needs throughout the transformation change bereavement process rather than only focusing on the initial stages characterized by intense emotion.


Tuning of thermo-responsive self-assembly monolayers on gold for cell-type-specific control of adhesion.
Self-assembled monolayers (SAMs) on gold containing a thermo-responsive poly( N-isopropylacrylamide)-poly(ethylene glycol)-thiol copolymer were formed. These layers show considerable potential for inducing enzyme-free and gentle detachment of cultivated cells. In an effort to optimize detachment of cells, including strongly adhering ones, two approaches are presented. First, two thermo-responsive copolymers with different poly(ethylene glycol) (PEG) contents of 15 wt % ("P15") and 19 wt % ("P19") were grafted to Au surfaces. Second, mixed monolayers were formed containing P19 and various concentrations of thiol bearing PEG. X-ray photoelectron spectroscopy (XPS) on pure and mixed P19 containing layers confirmed the expected layer compositions. Contact angle measurements showed good functionality of all surfaces prepared. Upon a temperature decrease below the lower critical solution temperature (LCST), the duration until cultivated fibroblasts detached from pure P19 surfaces was half of the one determined on P15. Strongly adherent human osteosarcoma cells could not be detached from pure P19 layers. Through co-adsorption of P19 and thiol-bearing PEG of a molar composition of 1:6, layers were formed that allowed good spreading of osteosarcoma cells above LCST and their efficient detachment below LCST.


[Prothrombin activation by immobilized thrombin].
The ability of thrombin, immobilized on BrCN-activated Sepharose 4B, to split prothrombin, was studied. Immobilized thrombin retained up to 70% of its esterase activity and about 5% of its coagulating activity; it was also found to induce partial proteolysis of prothrombin. Two products of prothrombin degradation isolated, i.e. P1 (m. w. 50.000-52.000) and P2 (m. w. 22.000-24.000), did not show either the thrombin or the prothrombin activities. P1 was converted into thrombin under the action of tripsin or Factor Xa. The rate of conversion was considerably increased after addition of Factor V, thromboplastin and Ca2+ ions. Intravenous administration of P1 to rats resulted in changes in the coagulating system of blood, which may be probably indicative of the stimulation of the anticoagulating system. P2 possessed no thrombogenic activity.


Al-induced proteomics changes in tomato plants over-expressing a glyoxalase I gene.
Glyoxalase I (Gly I) is the first enzyme in the glutathionine-dependent glyoxalase pathway for detoxification of methylglyoxal (MG) under stress conditions. Transgenic tomato 'Money Maker' plants overexpressing tomato SlGlyI gene (tomato unigene accession SGN-U582631/Solyc09g082120.3.1) were generated and homozygous lines were obtained after four generations of self-pollination. In this study, SlGlyI-overepxressing line (GlyI), wild type (WT, negative control) and plants transformed with empty vector (ECtr, positive control), were subjected to Al-treatment by growing in Magnavaca's nutrient solution (pH 4.5) supplemented with 20 µM Al3+ ion activity. After 30 days of treatments, the fresh and dry weight of shoots and roots of plants from Al-treated conditions decreased significantly compared to the non-treated conditions for all the three lines. When compared across the three lines, root fresh and dry weight of GlyI was significant higher than WT and ECtr, whereas there was no difference in shoot tissues. The basal 5 mm root-tips of GlyI plants expressed a significantly higher level of glyoxalase activity under both non-Al-treated and Al-treated conditions compared to the two control lines. Under Al-treated condition, there was a significant increase in MG content in ECtr and WT lines, but not in GlyI line. Quantitative proteomics analysis using tandem mass tags mass spectrometry identified 4080 quantifiable proteins and 201 Al-induced differentially expressed proteins (DEPs) in root-tip tissues from GlyI, and 4273 proteins and 230 DEPs from ECtr. The Al-down-regulated DEPs were classified into molecular pathways of gene transcription, RNA splicing and protein biosynthesis in both GlyI and ECtr lines. The Al-induced DEPs in GlyI associated with tolerance to Al3+ and MG toxicity are involved in callose degradation, cell wall components (xylan acetylation and pectin degradation), oxidative stress (antioxidants) and turnover of Al-damaged epidermal cells, repair of damaged DNA, epigenetics, gene transcription, and protein translation. A protein-protein association network was constructed to aid the selection of proteins in the same pathway but differentially regulated in GlyI or ECtr lines. Proteomics data are available via ProteomeXchange with identifiers PXD009456 under project title '25Dec2017_Suping_XSexp2_ITAG3.2' for SlGlyI-overexpressing tomato plants and PXD009848 under project title '25Dec2017_Suping_XSexp3_ITAG3.2' for positive control ECtr line transformed with empty vector.


Identification of low-frequency modes in protein molecules.
It is demonstrated that the observed low-frequency motions with wave numbers of 22 cm-1 and 25 cm-1 for insulin and lysozyme respectively originate from the accordion-like motions of the principal helices therein. The calculated results based on such a model are in good agreement with the observed values. During calculations the role of the internal microenvironment upon the low-frequency motion is naturally revealed, so as to elucidate as well why this kind of low-frequency motion is so sensitive to the conformations of proteins observed.


Changing patterns of prognosticators during 15-year follow-up of advanced gastric cancer after radical gastrectomy and adjuvant chemotherapy: a 15-year follow-up study at a single korean institute.
We evaluated the long-term natural history of gastric cancer after radical gastrectomy and adjuvant chemotherapy through a 15-year follow-up study at a single institute. Five hundred patients with advanced gastric adenocarcinoma who received radical gastrectomy and adjuvant chemotherapy were included in this long-term follow-up study. Patients were evaluated by imaging studies and upper gastrointestinal series or endoscopy every 6 months until the 10th year after surgery. Since then, the patients have been followed yearly in the same manner. The median follow-up period was 190.5 months. The recurrence rate in 5-year survivors was 10.8%. The dominant recurrence pattern was peritoneal carcinomatosis within 5 years and distant metastasis after 5 years post gastrectomy. Tumor stage was a clear-cut prognosticator within 5 years post gastrectomy, but was no longer informative in 5-10 years. At this period, only stage IV (IB-IIIB vs IVM0) was a significantly poor prognosticator. After 10 years, second primary cancer (seven cases) became as important an issue as recurrence of primary gastric cancer (six cases). In patients with gastric carcinoma treated with radical gastrectomy and adjuvant chemotherapy, late recurrence after 5 years post gastrectomy was not rare. Prognosticators were varied depending on the length of time after surgery. Tumor factors including stage were prognosticators within 5 years post gastrectomy, but tumor factors except stage IV had no prognostic value after 5 years. In the 5-10 years post gastrectomy, only stage IV (IB-IIIB vs IVM0) was a poor prognosticator. Also, after 10 years, there were no prognosticators.


The domain-specific probe EUB338 is insufficient for the detection of all Bacteria: development and evaluation of a more comprehensive probe set.
In situ hybridization with rRNA-targeted oligonucleotide probes has become a widely applied tool for direct analysis of microbial population structures of complex natural and engineered systems. In such studies probe EUB338 (AMANN et al., 1990) is routinely used to quantify members of the domain Bacteria with a sufficiently high cellular ribosome content. Recent reevaluations of probe EUB338 coverage based on all publicly available 16S rRNA sequences, however, indicated that important bacterial phyla, most notably the Planctomycetales and Verrucomicrobia, are missed by this probe. We therefore designed and evaluated two supplementary versions (EUB338-II and EUB338-III) of probe EUB338 for in situ detection of most of those phyla not detected with probe EUB338. In situ dissociation curves with target and non-target organisms were recorded under increasing stringency to optimize hybridization conditions. For that purpose a digital image software routine was developed. In situ hybridization of a complex biofilm community with the three EUB338 probes demonstrated the presence of significant numbers of probe EUB338-II and EUB338-III target organisms. The application of EUB338, EUB338-II and EUB338-III should allow a more accurate quantification of members of the domain Bacteria in future molecular ecological studies.


Novel methylation biomarker panel for the early detection of pancreatic cancer.
Pancreatic cancer is the fourth leading cause of cancer deaths and there currently is no reliable modality for the early detection of this disease. Here, we identify cancer-specific promoter DNA methylation of BNC1 and ADAMTS1 as a promising biomarker detection strategy meriting investigation in pancreatic cancer. We used a genome-wide pharmacologic transcriptome approach to identify novel cancer-specific DNA methylation alterations in pancreatic cancer cell lines. Of eight promising genes, we focused our studies on BNC1 and ADAMTS1 for further downstream analysis, including methylation and expression. We used a nanoparticle-enabled methylation on beads (MOB) technology to detect early-stage pancreatic cancers by analyzing DNA methylation in patient serum. We identified two novel genes, BNC1 (92%) and ADAMTS1 (68%), that showed a high frequency of methylation in pancreatic cancers (n = 143), up to 100% in PanIN-3 and 97% in stage I invasive cancers. Using the nanoparticle-enabled MOB technology, these alterations could be detected in serum samples (n = 42) from patients with pancreatic cancer, with a sensitivity for BNC1 of 79% [95% confidence interval (CI), 66%-91%] and for ADAMTS1 of 48% (95% CI, 33%-63%), whereas specificity was 89% for BNC1 (95% CI, 76%-100%) and 92% for ADAMTS1 (95% CI, 82%-100%). Overall sensitivity using both markers is 81% (95% CI, 69%-93%) and specificity is 85% (95% CI, 71%-99%). Promoter DNA methylation of BNC1 and ADAMTS1 is a potential biomarker to detect early-stage pancreatic cancers. Assaying the promoter methylation status of these genes in circulating DNA from serum is a promising strategy for early detection of pancreatic cancer and has the potential to improve mortality from this disease.


Static and dynamic balance control in older golfers.
To determine whether older golfers have better static and dynamic balance control than older but nongolfing healthy adults. Eleven golfers and 12 control participants (all male; 66.2 +/- 6.8 and 71.3 +/- 6.6 yr old, respectively) were recruited. Duration of static single-leg stance was timed. Control of body sway was assessed in single-leg stance during forward and backward platform perturbations. The lunge distance normalized with respect to each participant's height was used to compare the 2 groups in a forward-lunge test. Golfers maintained significantly longer duration in static single-leg stance. They achieved less anteroposterior body sway in perturbed single-leg stance and lunged significantly farther than did control participants. The better static and dynamic balance control exhibited by older golfers possibly reflects the effects of weight transfers from repeated golf swings during weight shift from 2-leg to predominantly 1-leg stance and from walking on uneven fairways.


Low-cost, high-precision micro-lensed optical fiber providing deep-micrometer to deep-nanometer-level light focusing.
A new type of micro-lensed optical fiber through stacking appropriate high-refractive microspheres at designed locations with respect to the cleaved end of an optical fiber is numerically and experimentally demonstrated. This new type of micro-lensed optical fiber can be precisely constructed with low cost and high speed. Deep micrometer-scale and submicrometer-scale far-field light spots can be achieved when the optical fibers are multimode and single mode, respectively. By placing an appropriate teardrop dielectric nanoscale scatterer at the far-field spot of this new type of micro-lensed optical fiber, a deep-nanometer near-field spot can also be generated with high intensity and minimum joule heating, which is valuable in high-speed, high-resolution, and high-power nanoscale detection compared with traditional near-field optical fibers containing a significant portion of metallic material.


Age-Related Changes in Headache Days across the Cognitive Spectrum.
Prior studies demonstrating age-related declines in headache prevalence have not accounted for the potentially confounding effects of cognitive impairment. Our primary goal was to assess the relationship between aging and self-reported monthly headache days across the cognitive spectrum. A detailed headache questionnaire was included prospectively as part of an annual mailing to participants in the Sanders-Brown Center on Aging longitudinal cohort. The overall survey response rate was 58.6%, yielding a cohort of 332 cognitively normal, 71 mild cognitive impairment (median Mini-Mental Status Examination [MMSE] score = 27, interquartile range [IQR] = 25-28), and 51 demented (median MMSE score = 24, IQR = 19-26) individuals. Current headaches were reported by 22.8%, 25%, and 27.1%, respectively, across normal, mild cognitive impairment, and dementia subgroups. A negative correlation was observed between age and average headache days in cognitively normal (ρ = -0.163, 95% confidence interval [CI] = -0.246 to -0.022, P = 0.004), mild cognitive impairment (ρ = -0.255, 95% CI = -0.274 to 0.229, P = 0.0475), and dementia groups (ρ = -0.295, 95% CI = -0.457 to 0.159, P = 0.068). Ordinary least-squares regression with backward selection identified age alone, but not gender or MMSE, as predicting headache days in the overall cohort. Aging is associated with a decline in headache days in the absence of any confounding cognitive pathology and is weakly predictive of headache days across the cognitive spectrum. Whether this represents a reporting bias due to dementia or has neurobiological significance warrants further investigation.


Compartment syndrome after South American rattlesnake (Crotalus durissus terrificus) envenomation.
In order to report the outcome of a patient who developed compartment syndrome after South American rattlesnake (Crotalus durissus terrificus) envenomation, confirmed by subfascial pressure measurement and magnetic resonance imaging (MRI). A 63-year-old male was admitted 1 h after being bitten on the right elbow by a "large" snake, which was not brought for identification. Physical and laboratory features upon admission revealed two fang marks, local tense swelling, paresthesia, intense local pain, hypertension, coagulopathy, and CK = 1530 U/L (RV < 170 U/L). The case was initially treated with bothropic antivenom (80 mL, intravenously), with no improvement. Evolution within 13-14 h post-bite revealed generalized myalgia, muscle weakness, palpebral ptosis, and severe rhabdomyolysis (CK = 126,160 U/L) compatible with envenoming by C. d. terrificus. The patient was then treated with crotalic antivenom (200 mL, intravenously), fluid replacement, and urine alkalinization. Twenty-four-hour post-bite MRI showed marked muscular edema in the anterior compartment of the right forearm, with a high subfascial pressure (40 mmHg) being detected 1 h later. ELISA of a blood sample obtained upon admission, before antivenom infusion, revealed a high serum concentration of C. d. terrificus venom. No fasciotomy was performed and the patient was discharged seven days later without sequelae. Snakebite by C. d. terrificus with subfascial venom injection may lead to increased intracompartmental pressure.


Factors associated with dental service use of older Korean Americans.
Based on Andersen's healthcare utilization model, the present study examined factors associated with dental service use in older Korean Americans. Focus was on predisposing characteristics (age, gender, marital status, education and region), oral health needs (problems with teeth or gums and self-rated oral health) and enabling factors (dental health insurance, length of stay in the United States, acculturation and family network). Using data from surveys with Korean Americans aged 60 or older (N = 2128), a Poisson regression model examined predictors of dental visit in the past 12 months. More than 21% of the sample reported having a problem with teeth or gums, and over half rated their oral health as either fair or poor. Approximately 71% lacked dental health insurance. The number of dental visits in the past 12 months averaged 1.40 (SD = 1.74), with about 38% having no dental visits at all. Multivariate analyses showed that higher levels of education, the presence of a problem with teeth or gums, dental health insurance coverage, longer length of stay in the United States, and larger family networks were associated with 1.01-1.35 times higher number of dental visits. The findings not only confirmed the critical role of dental health insurance as a service enabler but also highlighted the importance of considering older ethnic immigrants' oral health and dental care from the perspectives of culture and family.


The functional fitness capacity of adults with Down syndrome in South Africa.
It is well established that there is a relationship between physical inactivity and increased risk for diseases of lifestyle. Persons with Down syndrome (DS) are especially at risk because of physical and health impairments, as well as perceived and real barriers to participation in exercise. The purpose of the study was to establish the functional fitness capacity and predictors of performance of DS adults. Data were collected at various intellectual disability centres and private homes in seven provinces of South Africa. Three hundred and seventy-one DS individuals (199 men and 172 women) from 18 to 66 years were tested for balance, flexibility, coordination, muscular strength and endurance, aerobic capacity and functional ability. Data were categorised according to gender and age groups (18-25, 26-35, 36-45, and >45 years). Multiple regression analysis was performed to determine the relationship between the functional task and physical test items. Down syndrome men performed significantly better on all but two tests compared with the women (P < 0.05). DS women performed better on the sit-and-reach flexibility item and the chair stand test; however, differences were not statistically significant from the men. Significant differences across age groups were observed for nine of the 13 functional fitness tests (P < 0.05). Muscular strength items, especially leg strength, significantly predicted functional performance in DS men and women. Aerobic capacity only predicted functional performance in DS men and sit-and-reach flexibility and dynamic balance only in DS women. Findings of this study provide important information on the functional capacity of DS adults and show which physical attributes contribute to functional performance. Consequently appropriate training programmes can be tailored for this population whom is known to have poor functional fitness.


Murine retroviral restriction genes Fv-4 and Akvr-1 are alleles of a single locus.
The two murine retroviral restriction genes, Fv-4 and Akvr-1, are very similar in their effects, distributions, ranges of action, and phenotypes. Akvr-1 has been shown to segregate independently in backcrosses with a variety of retroviral restriction loci, including Fv-1, Fv-2, Ril-1, and Ril-2. An allelism test cross of FRG (Fv-4R) X LCRR (Akvr-1R) hybrids mated to AKR mice failed to produce any viremic offspring. These results suggested that Akvr-1R and Fv-4R are alleles of a single locus, Fv-4, on mouse chromosome 12.


Syndemic conditions and HIV transmission risk behavior among HIV-negative gay and bisexual men in a U.S. national sample.
The syndemics framework has been used to explain the high rates of HIV infection among gay and bisexual men. However, most studies have relied primarily on urban or otherwise limited (e.g., single location) samples. We evaluated the prevalence of syndemics-here, depression, polydrug use, childhood sexual abuse, intimate partner violence, and sexual compulsivity-among gay and bisexual men from across the United States, including nonurban areas. Using data from a national sample of 1,033 HIV-negative gay and bisexual men, demographic differences in the prevalence of each syndemic condition and associations with HIV transmission risk behavior were examined. More than 62% of men reported at least 1 syndemic condition. Prevalence did not vary by U.S. region-however, a larger proportion of nonurban men and those with lower income and education levels were above the median number of syndemic conditions. In bivariate analyses, HIV transmission risk behavior was associated with each syndemic condition except for childhood sexual abuse, whereas in multivariate analyses, it was associated with polydrug use, sexual compulsivity, being Latino, and being single and was highest among those reporting 3 or more syndemic conditions. Rates of syndemic conditions among this national sample of gay and bisexual men were generally comparable to previous studies, however elevated rates in nonurban men suggest the need for targeted intervention and support. Links observed between syndemics and HIV transmission risk behavior highlight the ongoing need to address psychosocial concerns among gay and bisexual men in order to reduce their disproportionately high rates of HIV infection. (PsycINFO Database Record


A n-3 PUFA depletion applied to rainbow trout fry (Oncorhynchus mykiss) does not modulate its subsequent lipid bioconversion capacity.
Nutritional strategies are currently developed to produce farmed fish rich in n-3 long-chain PUFA (LC-PUFA) whilst replacing fish oil by plant-derived oils in aquafeeds. The optimisation of such strategies requires a thorough understanding of fish lipid metabolism and its nutritional modulation. The present study evaluated the fatty acid bioconversion capacity of rainbow trout (Oncorhynchus mykiss) fry previously depleted in n-3 PUFA through a 60-d pre-experimental feeding period with a sunflower oil-based diet (SO) followed by a 36-d experimental period during which fish were fed either a linseed oil-based diet (LO) (this treatment being called SO/LO) or a fish oil-based diet (FO) (this treatment being called SO/FO). These treatments were compared with fish continuously fed on SO, LO or FO for 96 d. At the end of the 36-d experimental period, SO/LO and SO/FO fish recovered >80 % of the n-3 LC-PUFA reported for LO and FO fish, respectively. Fish fed on LO showed high apparent in vivo elongation and desaturation activities along the n-3 biosynthesis pathway. However, at the end of the experimental period, no impact of the fish n-3 PUFA depletion was observed on apparent in vivo elongation and desaturation activities of SO/LO fish as compared with LO fish. In contrast, the fish n-3 PUFA depletion negatively modulated the n-6 PUFA bioconversion capacity of fish in terms of reduced apparent in vivo elongation and desaturation activities. The effects were similar after 10 or 36 d of the experimental period, indicating the absence of short-term effects.


Evaluation of a risk-stratification strategy to improve primary care for low back pain: the MATCH cluster randomized trial protocol.
Despite numerous options for treating back pain and the increasing healthcare resources devoted to this problem, the prevalence and impact of back pain-related disability has not improved. It is now recognized that psychosocial factors, as well as physical factors, are important predictors of poor outcomes for back pain. A promising new approach that matches treatments to the physical and psychosocial obstacles to recovery, the STarT Back risk stratification approach, improved patients' physical function while reducing costs of care in the United Kingdom (UK). This trial evaluates implementation of this strategy in a United States (US) healthcare setting. Six large primary care clinics in an integrated healthcare system in Washington State were block-randomized, three to receive an intensive quality improvement intervention for back pain and three to serve as controls for secular trends. The intervention included 6 one-hour training sessions for physicians, 5 days of training for physical therapists, individualized and group coaching of clinicians, and integration of the STarT Back tool into the electronic health record. This prognostic tool uses 9 questions to categorize patients at low, medium or high risk of persistent disabling pain with recommendations about evidence-based treatment options appropriate for each subgroup. Patients at least 18 years of age, receiving primary care for non-specific low back pain, were invited to provide data 1-3 weeks after their primary care visit and follow-up data 2 months and 6 months (primary endpoint) later. The primary outcomes are back-related physical function and pain severity. Using an intention to treat approach, intervention effects on patient outcomes will be estimated by comparing mean changes at the 2 and 6 month follow-up between the pre- and post-implementation periods. The inclusion of control clinics permits adjustment for secular trends. Differences in change scores by intervention group and time period will be estimated using linear mixed models with random effects. Secondary outcomes include healthcare utilization and adherence to clinical guidelines. This trial will provide the first randomized trial evidence of the clinical effectiveness of implementing risk stratification with matched treatment options for low back pain in a United States health care delivery system. NCT02286141. Registered November 5, 2014.


Biosynthesis of JC-La2CoO4 magnetic nanoparticles explored in catalytic and SMMs properties.
We have reported the synthesis of JC-La2CoO4 magnetic nanoparticles from Jatropha Curcas L. leaf extract in aqueous medium and potential application study in catalytic & Single Molecule Magnets (SMMs). Several techniques were used to investigate the structural, morphological, and elemental composition, particle size, optical properties, catalytic and magnetic properties by XRD, FTIR, SEM, EDAX, XPS, UV-visible and squid magnetic measurement. It was found that the crystallite sizes and grain sizes of JC-La2CoO4 NPs were 11.3 ± 1 and 24.1 ± 1 nm respectively and surface morphology of the nanoparticles looks spherical shape with good surface area. The band gap of JC-La2CoO4 was found to be 4.95 eV indicates good semiconductor in nature. XPS studies shows that La and Co present in + 3 and + 2 oxidation state respectively and suggest the composition formula is La2CoO4 with satisfied all the valency of metal ions. The photocatalytic efficiency of La2CoO4 shows good result against methylene blue (MB) compared to other dyes like MO, NO, RhB in presence of sunlight with rate constant 56.73 × 10-3 min-1 and completely degraded within 115 mints. The importance of JC-La2CoO4 has magnetic properties with antiferromagnetic coupling and SMMs properties with nature.


Ethics in obstetrics and gynecology. An overview.
This paper provides an overview of ethical issues in obstetrics and gynecology. We first define two basic ethical principles, beneficence and respect for autonomy. We first apply these principles to gynecologic practice, emphasizing the role of informed consent. We then apply these principles to obstetric practice, utilizing the concept of the fetus as a patient and identifying its clinical implications for directive versus non-directive counseling for fetal benefit.


The role of CD11a/CD18-CD54 interactions in human T cell-dependent B cell activation.
The role of leukocyte function-associated Ag-1 (LFA-1, CD11a/CD18) and intercellular adhesion molecule 1 (ICAM-1, CD54) interactions in human T cell and B cell collaboration was examined by studying the effect of mAb to these determinants on B cell proliferation and differentiation stimulated by culturing resting B cells with CD4+ T cells activated with immobilized mAb to the CD3 molecular complex. In this model system, mAb to either the alpha (CD11a) or beta (CD18) chain of LFA-1 or ICAM-1 (CD54) inhibited B cell responses significantly. The mAb did not directly inhibit B cell function, inasmuch as T cell-independent activation induced by formalinized Staphylococcus aureus and IL-2 was not suppressed. Moreover, DNA synthesis and IL-2 production by immobilized anti-CD3-stimulated CD4+ T cells were not suppressed by the mAb to LFA-1 or ICAM-1. Although the mAb to LFA-1 inhibited enhancement of IL-2 production by co-culture of immobilized anti-CD3-stimulated CD4+ T cells with B cells, addition of exogenous IL-2 or supernatants of mitogen-activated T cells could not abrogate the inhibitory effects of the mAb to LFA-1 or ICAM-1 on B cell responses. Inhibition was most marked when the mAb were present during the initial 24 h in culture. Immobilized anti-CD3-stimulated LFA-1-negative CD4+ T cell clones from a child with leukocyte adhesion deficiency could induce B cell responses, which were inhibited by mAb to LFA-1 or ICAM-1. These results indicate that the interactions between LFA-1 and ICAM-1 play an important role in mediating the collaboration between activated CD4+ T cells and B cells necessary for the induction of B cell proliferation and differentiation, and for enhancement of IL-2 production by CD4+ T cells. Moreover, the data are consistent with a model of T cell-B cell collaboration in which interactions between LFA-1 on resting B cells and ICAM-1 on activated CD4+ T cells play a critical role in initial T cell-dependent B cell activation.


ALK-Negative Anaplastic Large Cell Lymphoma Presenting as an Extranodal Soft-Tissue Mass With an Unusual Alveolar Growth Pattern: A Diagnostic Challenge.
Anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma which has been recognized to have a variable clinical presentation and a broad spectrum of histomorphologic features. Its variable histomorphologic appearances are sometimes diagnostically challenging for the pathologists since they can mimic sarcomas, melanomas and undifferentiated carcinomas. To our knowledge, a previous case of axillary soft-tissue mass of ALK-positive ALCL with an alveolar growth pattern has been so far reported in the literature. This alveolar appearance is unusual for ALCL. It can impose a diagnostic pitfall, particularly in extranodal soft-tissue masses. We report a case of ALK-negative ALCL that presented as an extranodal soft-tissue neck mass in an adult man. Histologically, it showed a characteristic alveolar growth pattern composed of well-defined nests of dyscohesive highly pleomorphic large neoplastic cells separated by thin fibrovascular septae. Morphologically, it mimicked sarcomas, carcinomas, melanoma and germ cell neoplasms. Initially, a histologic diagnosis of ALCL was not considered. However, the negative immunomarkers for the above mimickers and the strong CD30 positivity have raised the suspicion of anaplastic lymphomas. Further immunohistochemistry studies showed the neoplastic cells to be positive for CD4 and CD43. This case report emphasizes the potential diagnostic pitfalls associated with an ALK-negative ALCL when manifests as a soft-tissue mass with an alveolar growth pattern. Pathologists should be aware of this uncommon growth pattern in ALCLs. They should implement a broad panel of immunomarkers in soft-tissue masses of anaplastic pleomorphic cells with an alveolar morphology.


Requirements for the solubilization of immune aggregates by complement: assembly of a factor B-dependent C3-convertase on the immune complexes.
During the solubilization of immune precipitates BSA-rabbit antibodies to BSA by human complement, at least three stages can be distinguished. (A) Generation of alternative pathway C3-convertase sites associated with the immune complexes. During the first minutes of interaction between the immune aggregates and serum, before any solubilization has taken place, properdin (P), factor B, and C3 moieties are incorporated into the lattice. The washed precipitates have C3-convertase activity, which can be completely inhibited by antibodies to factor B, but not to C2. The assembly of the convertase is temperature-dependent, and does not take place in the absence of Mg++. The immune complex-associated C3-convertase activity decays rapidly at 37 degrees C, but it can be restored by addition of purified factor B and properdin. (B) Amplification. When the aggregates bearing C3-convertase are incubated with purified C3, solubilization takes place. It appears that solubilization is caused by the accumulation of a large number of C3 fragments on the Ag-Ab lattice. In solubilized complexes, the molar ratios of Ab/C3 are close to one. (C) Spontaneous release. The final step in the solubilization process is a secondary reaction, during which some rearrangement of the lattice takes place. It occurs in medium devoid of serum and does not require divalent cations.


Marjoram increases basal gastric acid and pepsin secretions in rat.
Considering the high consumption rate of marjoram in the Iranian population, this study was designed to investigate the effects of marjoram extract on gastric acid and pepsin secretion. In this study, Wistar rats (n=12) were divided into two equal case and control groups. Under general anaesthesia with 50 mg/kg i.p. sodium thiopental, laparatomy was done and a cannula inserted in the duodenum. In the case animals marjoram (12.5 mg/kg) was injected into the stomach through the mentioned cannula. The gastric contents were collected by the wash-out technique. Acid and pepsin secretions were then measured by titration and the Anson method, respectively. In the marjoram group, basal acid and pepsin secretions were significantly increased compared with the control group (acid: 20+/-3.36 vs 4.1+/-0.36 micromol/15 min; pepsin: 9.04+/-0.01 vs 5.62+/-0.12 microg/15 min; p<0.001). In the control group, pentagastrin stimulation increased acid secretion in comparison with the basal level (10.14+/-1.34 vs 4.1+/-0.36 micromol/15 min, p<0.001), while in the marjoram group, there was a significant decline (16.46+/-3.23 vs 20+/-3.36 micromol/15 min, p<0.001). In the marjoram group pentagastrin increased pepsin secretion in comparison with the basal state (12+/-0.11 vs 9.04+/-0.1 microg/15 min, p<0.001). It seems that marjoram contains some components that activate chief and parietal cells and increase basal acid and pepsin secretion.


How Are Preferences Revealed?
Revealed preferences are tastes that rationalize an economic agent's observed actions. Normative preferences represent the agent's actual interests. It sometimes makes sense to assume that revealed preferences are identical to normative preferences. But there are many cases where this assumption is violated. We identify five factors that increase the likelihood of a disparity between revealed preferences and normative preferences: passive choice, complexity, limited personal experience, third-party marketing, and intertemporal choice. We then discuss six approaches that jointly contribute to the identification of normative preferences: structural estimation, active decisions, asymptotic choice, aggregated revealed preferences, reported preferences, and informed preferences. Each of these approaches uses consumer behavior to infer some property of normative preferences without equating revealed and normative preferences. We illustrate these issues with evidence from savings and investment outcomes.


Disulphide cross-linking of smooth-muscle and non-muscle caldesmon to the C-terminus of actin in reconstituted and native thin filaments.
It was reported that chicken gizzard smooth-muscle caldesmon Cys-580 can be disulphide-cross-linked to the C-terminal pen-ultimate residue (Cys-374) of actin, indicating that these residues are close in the protein complex [Graceffa, P. and Jancso, A. (1991) J. Biol. Chem. 266, 20305-20310]. Since the possibility that the cross-link involves a cysteine residue other than actin Cys-374 was not absolutely excluded, more direct evidence was sought for the identify of the cysteine residues involved in the cross-link. We show here that caldesmon could not be disulphide-cross-linked to actin which had Cys-374 removed by carboxypeptidase A digestion, providing direct support for the participation of actin Cys-374 in the cross-link to caldesmon. In order to assign the caldesmon cysteine residue involved in the cross-link, use was made of caldesmon from porcine stomach muscle, which is shown to contain one cysteine residue close to, or at, position 580, in contrast with chicken gizzard caldesmon, which has an additional cysteine residue at position 153. The porcine stomach caldesmon also formed a disulphide-cross-link to actin, further supporting the original conclusion that Cys-580 of the chicken gizzard caldesmon had been cross-linked to actin. Disulphide-cross-linking with similar yield was also observed in native chicken gizzard muscle thin filaments, indicating that the interaction between actin and the C-terminal domain of caldesmon is the same in native and reconstituted thin filaments. The much smaller non-muscle isoform of caldesmon, from rabbit liver, could be similarly cross-linked to actin, consistent with the sequence similarity between the C-terminal domain of muscle and non-muscle caldesmon. The ability to cross-link caldesmon Cys-580 to actin Cys-374 suggests the possibility that the Cys-580 region of caldesmon and the C-terminus of actin form part of the actin-caldesmon binding interface.


Neuronal expression of neural nitric oxide synthase (nNOS) protein is suppressed by an antisense RNA transcribed from an NOS pseudogene.
Here, we show that a nitric oxide synthase (NOS) pseudogene is expressed in the CNS of the snail Lymnaea stagnalis. The pseudo-NOS transcript includes a region of significant antisense homology to a previously reported neuronal NOS (nNOS)-encoding mRNA. This suggested that the pseudo-NOS transcript acts as a natural antisense regulator of nNOS protein synthesis. In support of this, we show that both the nNOS-encoding and the pseudo-NOS transcripts are coexpressed in giant identified neurons (the cerebral giant cells) in the cerebral ganglion. Moreover, reverse transcription-PCR experiments on RNA isolated from the CNS establish that stable RNA-RNA duplex molecules do form between the two transcripts in vivo. Using an in vitro translation assay, we further demonstrate that the antisense region of the pseudogene transcript prevents the translation of nNOS protein from the nNOS-encoding mRNA. By analyzing NOS RNA and nNOS protein expression in two different identified neurons, we find that when both the nNOS-encoding and the pseudo-NOS transcripts are present in the same neuron, nNOS enzyme activity is substantially suppressed. Importantly, these results show that a natural antisense mechanism can mediate the translational control of nNOS expression in the Lymnaea CNS. Our findings also suggest that transcribed pseudogenes are not entirely without purpose and are a potential source of a new class of regulatory gene in the nervous system.


[Control of iron deficiency in developing countries].
Iron deficiency is the most prevalent nutritional disorder worldwide, especially in developing countries. It occurs when iron absorption cannot compensate iron requirements and losses. Requirements are especially high in pregnant women, infants, young children and adolescents who run a higher risk of being iron-deficient. In developing countries, the main cause of iron deficiency is the low iron bioavailability of the diet. The consequences of iron deficiency are many and serious, affecting not only individuals' health but also the development of societies and countries. The prevention and the control of iron deficiency and anemia in all groups of a population with different iron requirements imply to coordinate different interventions. Iron fortification of staple foods or condiments directed to the whole population is a sustainable and low cost-effective approach. However, at some periods of life, especially during pregnancy and in children from the age of 6 months, iron requirements are high. For pregnant women, the current approach favours the daily iron-folate supplementation during pregnancy but the results in terms of public health are disappointing. The preventive weekly iron-folate supplementation of women during their reproductive life, whose efficacy is recognized, offers a promising alternative; its impact in terms of public health is under current evaluation. For infants and young children, iron fortification of complementary food is effective but this food is generally imported and economically inaccessible to populations with limited resources. The production, by small private units from local products, of complementary foods of low viscosity, good nutritional quality, fortified with vitamins and minerals, and of low cost is at hand in several countries. When complementary foods are not available, the preventive iron supplementation from 6 to 18 months of age has to be advised. This approach should be strengthened by the advantages of the weekly approach. These interventions are more effective when they integrate other approaches like the improvement of the nutritional practices, infection control and the promotion of breast-feeding and when coupled with programs aiming to control other micronutrient deficiencies. The success of most interventions requires the active participation of the individuals. Information and education of the populations, especially through social mobilization campaigns, are essential because iron deficiency induces few visible symptoms, not easily recognizable by individuals. The implementation of national nutrition plans including the control of iron deficiency as one of the priorities and the participation of the public health and education sectors, food industries, the community and the media should contribute to the success of the interventions and to the control of iron deficiency.


Positive inotropic effects of low concentrations of leukotrienes C4 and D4 in rat heart.
We examined the effects of leukotrienes (LT) B4, C4, D4, and E4 (0.010-2.5 ng/ml) on contractile and coronary function in isolated rat hearts. Concentration-dependent effects were examined either by the cumulative addition of LTs or by addition of specific concentrations to individual preparations. Neither LTB4 nor LTE4 produced myocardial or coronary effects at any concentration, irrespective of addition protocol. At 0.010 ng/ml, both LTC4 and LTD4 produced an increase in force that was associated with a 30% elevation in coronary pressure. Further cumulative addition of either leukotriene resulted in a negative inotropic effect and a further increase in coronary pressure. In contrast, following single additions of LTC4 or LTD4 (0.01-0.50 ng/ml) a positive inotropic effect and an increased coronary pressure were observed. LTC4 or LTD4 at 0.5 ng/ml produced a negative inotropic effect in hearts pretreated with 0.01 ng/ml of LTD4 or LTC4, respectively. Reversal of this addition protocol resulted in a negative inotropic effect of either 0.01 ng/ml LTD4 or LTC4. Verapamil and nifedipine significantly attenuated the positive inotropic and coronary constricting effect of 0.5 ng/ml LTC4 and LTD4. The addition of either LT following BAY K 8644 resulted in a negative inotropic effect, in contrast to the positive inotropic influence seen with leukotriene alone. Our results demonstrate a positive inotropic effect of low concentrations of LTC4 and LTD4 concomitant with coronary artery constriction, a phenomenon determined by leukotriene addition protocols and suggestive of LTC4/LTD4 receptor interaction. The effects of calcium channel antagonists and BAY K 8644 on the inotropic response suggest a leukotriene-mediated activation of the calcium channel resulting in increased intracellular calcium concentrations.


A Stereoselective aza-Prins Reaction: Rapid Access to Enantiopure Piperidines and Pipecolic Acids.
The aza-Prins reaction is a widely employed and highly efficient method for the preparation of saturated nitrogen-containing heterocycles. Its major drawback has always been a lack of diastereoselectivity and the formation of racemic products. Herein, we address these problems and report, for the first time, the synthesis of both diastereomerically and enantiopure multiply substituted piperidines via the aza-Prins reaction. This method is widely applicable for natural product synthesis and is exemplified here by the synthesis of enantiopure pipecolic acid derivatives.


Initial disease course and treatment in an inflammatory bowel disease inception cohort in Europe: the ECCO-EpiCom cohort.
The EpiCom cohort is a prospective, population-based, inception cohort of inflammatory bowel disease (IBD) patients from 31 European centers covering a background population of 10.1 million. The aim of this study was to assess the 1-year outcome in the EpiCom cohort. Patients were followed-up every third month during the first 12 (±3) months, and clinical data, demographics, disease activity, medical therapy, surgery, cancers, and deaths were collected and entered in a Web-based database (www.epicom-ecco.eu). In total, 1367 patients were included in the 1-year follow-up. In western Europe, 65 Crohn's disease (CD) (16%), 20 ulcerative colitis (UC) (4%), and 4 IBD unclassified (4%) patients underwent surgery, and in eastern Europe, 12 CD (12%) and 2 UC (1%) patients underwent surgery. Eighty-one CD (20%), 80 UC (14%), and 13 (9%) IBD unclassified patients were hospitalized in western Europe compared with 17 CD (16%) and 12 UC (8%) patients in eastern Europe. The cumulative probability of receiving immunomodulators was 57% for CD in western (median time to treatment 2 months) and 44% (1 month) in eastern Europe, and 21% (5 months) and 5% (6 months) for biological therapy, respectively. For UC patients, the cumulative probability was 22% (4 months) and 15% (3 months) for immunomodulators and 6% (3 months) and 1% (12 months) for biological therapy, respectively in the western and eastern Europe. In this cohort, immunological therapy was initiated within the first months of disease. Surgery and hospitalization rates did not differ between patients from eastern and western Europe, although more western European patients received biological agents and were comparable to previous population-based inception cohorts.


Immature lung problems: can our nomenclature be more specific?
Since the advent of surfactant therapy for hyaline membrane disease, the problems associated with this condition have been greatly reduced in severity and morbidity. However, many premature infants who recover from the biochemical problem of surfactant deficiency still suffer from structural immaturity of the lungs. This aspect of lung immaturity centers primarily around pulmonary hypoplasia, for these infants, because they are immature, have fewer than normal alveoli and thus cannot accomplish adequate gas exchange. As a result, they are placed on long-term ventilator therapy, which renders them susceptible to problems associated with hypoxia, oxygen toxicity, and barotrauma. Over the last two decades, we have learned a great deal about the pathophysiology of these problems, and we believe that the terminology used to describe them may now be less than accurate. We suggest that the it be adjusted to more correctly reflect the problems seen in these infants.


Importance and estimation of aerosol vertical structure in satellite ocean-color remote sensing.
The vertical distribution of absorbing aerosols affects the reflectance of the ocean-atmosphere system. The effect, due to the coupling between molecular scattering and aerosol absorption, is important in the visible, especially in the blue, where molecular scattering is effective, and becomes negligible in the near infrared. It increases with increasing Sun and view zenith angles and aerosol optical thickness and with decreasing scattering albedo but is practically independent of wind speed. Relative differences between the top of the atmosphere reflectance simulated with distinct vertical distributions may reach approximately 10% or even 20%, depending on aerosol absorption. In atmospheric correction algorithms, the differences are directly translated into errors on the retrieved water reflectance. These errors may reach values well above the 5x10(-4) requirement in the blue, even for small aerosol optical thickness, preventing accurate retrieval of chlorophyll-a [Chl-a] concentration. Estimating aerosol scale height or altitude from measurements in the oxygen A band, possible with the polarization and directionality of the Earth's reflectance instrument and medium resolution imaging spectrometer, is expected to improve significantly the accuracy of the water reflectance retrievals and yield acceptable [Chl-a] concentration estimates in the presence of absorbing aerosols.


Effects of penehyclidine hydrochloride on rat intestinal barrier function during cardiopulmonary bypass.
To test the ability of penehyclidine hydrochloride (PHC) to attenuate intestinal injury in a rat cardiopulmonary bypass (CPB) model. Male Sprague-Dawley rats were randomly divided into six groups (eight each): sham-operated control; sham-operated low-dose PHC control (0.6 mg/kg); sham-operated high-dose PHC control (2.0 mg/kg); CPB vehicle control; CPB low-dose PHC (0.6 mg/kg); and CPB high-dose PHC (2.0 mg/kg). Blood samples were collected from the femoral artery 2 h after CPB for determination of plasma diamine oxidase (DAO), D-lactate and endotoxin levels. Spleen, liver, mesenteric lymph nodes and lung were removed for biochemical analyses. Intestinal tissue ultrastructure was examined by electron microscopy. In the sham-operated groups, high- and low-dose-PHC had no significant impact on the levels of DAO, D-lactate and endotoxin, or the incidence of intestinal bacterial translocation (BT). Serum levels of DAO, D-lactate, endotoxin and the incidence of intestinal BT were significantly increased in the surgical groups, compared with the sham-operated groups (0.543 ± 0.061, 5.697 ± 0.272, 14.75 ± 2.46, and 0/40 vs 1.038 ± 0.252, 9.377 ± 0.769, 60.37 ± 5.63, and 30/40, respectively, all P < 0.05). PHC alleviated the biochemical and histopathological changes in a dose-dependent manner. Serum levels of DAO, D-lactate, and endotoxin and the incidence of intestinal BT in the high-dose PHC group were significantly lower than in the low-dose PHC group (0.637 ± 0.064, 6.972 ± 0.349, 29.64 ± 5.49, and 14/40 vs 0.998 ± 0.062, 7.835 ± 0.330, 38.56 ± 4.28, and 6/40, respectively, all P < 0.05). PHC protects the structure and function of the intestinal mucosa from injury after CPB in rats.


beta-carotene attenuates the paradoxical effect of tobacco smoke on the mortality of rats after experimental myocardial infarction.
The objective of this study was to investigate the effects of exposure to tobacco smoke (ETS) in rats that were or were not supplemented with dietary beta-carotene (BC), on ventricular remodeling and survival after myocardial infarction (MI). Rats (n = 189) were allocated to 4 groups: the control group, n = 45; group BC administered 500 mg/kg diet, n = 49, BC supplemented rats; group ETS, n = 55, rats exposed to tobacco smoke; and group BC+ETS, n = 40. Wistar rats weighing 100 g were administered one of the treatments until they weighed 200 to 250 g (approximately 5 wk). The ETS rats were exposed to cigarette smoke for 30 min 4 times/d, in a chamber connected to a smoking device. After reaching a weight of 200-250 g, rats were subjected to experimental MI (coronary artery occlusion) and mortality rates were determined over the next 105 d. In addition, echocardiographic, isolated heart, morphometrical, and biochemical studies were performed. Mortality data were tested using Kaplan-Meyer curves and other data by 2-way ANOVA. Survival rates were greater in the ETS group (58.2%) than in the control (33.3%) (P = 0.001) and BC+ETS rats (30.0%) (P = 0.007). The groups did not differ in the other comparisons. Left ventricular end-diastolic diameter normalized to body weight was greater and maximal systolic pressures were lower in the ETS groups than in non-ETS groups. Previous exposure to tobacco smoke induced a process of cardiac remodeling after MI. There is a paradoxical protector effect with tobacco smoke exposure, characterized by lower mortality, which is offset by BC supplementation.


[Closure of Patent Foramen Ovale after Ischemic Stroke].
Secondary prevention of otherwise cryptogenic stroke in patients with patent foramen ovale (PFO) has been a matter of debate over nearly three decades. Main issues were that data essentially derived from case-control-studies for a long period and that results from the randomized controlled trials CLOSURE-I, PC Trial and RESPECT, which were published in 2012 and 2013, were interpreted in different ways. The likewise not blinded randomized controlled trials REDUCE, CLOSE and DEFENSE-PFO, which were published in 2017 and 2018, consistently demonstrated superiority of interventional PFO closure compared to secondary stroke prevention with antiplatelet therapy in patients 18 to 60 years with cryptogenic stroke and moderate to severe atrial right-to-left shunt. Consecutively, the German Society of Cardiology, the German Society of Neurology and the German Stroke Society published joint recommendations strongly recommending interventional PFO closure in these patients. This review article briefly summarizes current scientific knowledge. Furthermore, open questions regarding secondary prevention in otherwise cryptogenic stroke patients with PFO are discussed.


PutidaNET: interactome database service and network analysis of Pseudomonas putida KT2440.
Pseudomonas putida KT2440 (P. putida KT2440) is a highly versatile saprophytic soil bacterium. It is a certified bio-safety host for transferring foreign genes. Therefore, the bacterium is used as a model organism for genetic and physiological studies and for the development of biotechnological applications. In order to provide a more systematic application of the organism, we have constructed a protein-protein interaction (PPI) network analysis system of P. putida KT2440. PutidaNET is a comprehensive interaction database and server of P. putida KT2440 which is generated from three protein-protein interaction (PPI) methods. We used PSIMAP (Protein Structural Interactome MAP), PEIMAP (Protein Experimental Interactome MAP), and Domain-domain interactions using iPfam. PutidaNET contains 3,254 proteins, and 82,019 possible interactions consisting of 61,011 (PSIMAP), 4,293 (PEIMAP), and 30,043 (iPfam) interaction pairs except for self interaction. Also, we performed a case study by integrating a protein interaction network and experimental 1-DE/MS-MS analysis data P. putida. We found that 1) major functional modules are involved in various metabolic pathways and ribosomes, and 2) existing PPI sub-networks that are specific to succinate or benzoate metabolism are not in the center as predicted. We introduce the PutidaNET which provides predicted interaction partners and functional analyses such as physicochemical properties, KEGG pathway assignment, and Gene Ontology mapping of P. putida KT2440 PutidaNET is freely available at http://sequenceome.kobic.kr/PutidaNET.


Pigmented mammary Paget's disease mimicking melanoma.
Our case of pigmented mammary Paget's disease simulated melanoma clinically and dermoscopically. Histologically, the lesion was characterized by microscopic features similar to those seen in malignant melanoma and, to a lesser extent, in Bowen's disease (intra-epidermal squamous cell carcinoma). Immunohistochemical studies demonstrated that the tumor cells were positive for keratins (Cam 5.2+MNF 116) and AE1-AE3 and negative for HMB-45 and S-100 proteins. In conclusion clinical and dermoscopic examination cannot reliably distinguish melanoma from epithelial pre-neoplastic or neoplastic disease, therefore the differentiation of pigmented Paget's disease from superficial spreading of melanoma and Bowen's disease is based on histopathologic integrated with immunohistochemical criteria.


Inhibitory effects of different forms of tocopherols, tocopherol phosphates, and tocopherol quinones on growth of colon cancer cells.
Tocopherols are the major source of dietary vitamin E. In this study, the growth inhibitory effects of different forms of tocopherols (T), tocopheryl phosphates (TP), and tocopherol quinones (TQ) on human colon cancer HCT116 and HT29 cells were investigated. δ-T was more active than γ-T in inhibiting colon cancer cell growth, decreasing cancer cell colony formation, and inducing apoptosis; however, α-T was rather ineffective. Similarly, the rate of cellular uptake also followed the ranking order δ-T > γ-T ≫ α-T. TP and TQ generally had higher inhibitory activities than their parent compounds. Interestingly, the γ forms of TP and TQ were more active than the δ forms in inhibiting cancer cell growth, whereas the α forms were the least effective. The potencies of γ-TQ and δ-TQ (showing IC50 values of ∼0.8 and ∼2 μM on HCT116 cells after a 72 h incubation, respectively) were greater than 100-fold and greater than 20-fold higher, respectively, than those of their parent tocopherols. Induction of cancer cell apoptosis by δ-T, γ-TP, and γ-TQ was characterized by the cleavage of caspase 3 and PARP1 and DNA fragmentation. These studies demonstrated the higher growth inhibitory activity of δ-T than γ-T, the even higher activities of the γ forms of TP and TQ, and the ineffectiveness of the α forms of tocopherol and their metabolites against colon cancer cells.