Tumor-Associated Disialylated Glycosphingolipid Antigen-Revealing Antibodies Found in Melanoma Patients' Immunoglobulin Repertoire Suggest a Two-Direction Regulation Mechanism Between Immune B Cells and the Tumor.
There is far less information available about the tumor infiltrating B (TIL-B) cells, than about the tumor infiltrating T cells. We focused on discovering the features and potential role of B lymphocytes in solid tumors. Our project aimed to develop innovative strategies to define cancer membrane structures. We chose two solid tumor types, with variable to considerable B cell infiltration. The strategy we set up with invasive breast carcinoma, showing medullary features, has been introduced and standardized in metastatic melanoma. After detecting B lymphocytes by immunohistochemistry, VH-JH, Vκ-Jκ immunoglobulin rearranged V region genes were amplified by RT-PCR, from TIL-B cDNA. Immunoglobulin variable-region genes of interest were cloned, sequenced, and subjected to a comparative DNA analysis. Single-chain variable (scFv) antibody construction was performed in selected cases to generate a scFv library and to test tumor binding capacity. DNA sequence analysis revealed an overrepresented VH3-1 cluster, represented both in the breast cancer and the melanoma TIL-B immunoglobulin repertoire. We observed that our previously defined anti GD3 ganglioside-binder antibody-variable region genes were present in melanoma as well. Our antibody fragments showed binding potential to disialylated glycosphingolipids (GD3 ganglioside) and their O acetylated forms on melanoma cancer cells. We conclude that our results have a considerable tumor immunological impact, as they reveal the power of TIL-B cells to recognize strong tumor-associated glycosphingolipid structures on melanomas and other solid tumors. As tumor-derived gangliosides affect immune cell functions and reduce the B lymphocytes' antibody production, we suspect an important B lymphocyte and cancer cell crosstalk mechanism. We not only described the isolation and specificity testing of the tumor infiltrating B cells, but also showed the TIL-B cells' highly tumor-associated GD3 ganglioside-revealing potential in melanomas. The present data help to identify new cancer-associated biomarkers that may serve for novel cancer diagnostics. The two-direction regulation mechanism between immune B cells and the tumor could eventually be developed into an innovative cancer treatment strategy.


Animals as models of age-related macular degeneration: an imperfect measure of the truth.
Age-related macular degeneration (AMD) is a degenerative condition that begins in Bruch's membrane and progresses to involve the retinal pigment epithelium and ultimately the overlying photoreceptors. The only required etiologic factor is age, and AMD is regarded as the leading cause of blindness in individuals older than 65 years. AMD results from variable contributions of age, environment, and genetic predisposition. Many loci are linked to AMD; in the majority of cases, the disease is associated with polymorphisms within these genes, rather than mutations that ablate gene function. The etiologic complexity of AMD is reflected by the paucity of animal models that entirely replicate the human disease. This review compares the salient anatomy of the primate and rodent retina, particularly in the light of AMD pathology. It next discusses prevailing hypotheses explaining how AMD may develop. These include the role of complement activation and macrophage chemotaxis in AMD, molecular mechanisms of choroidal neovascularization, and the roles of oxidative damage and lipid metabolism. Finally, the article gives an overview of spontaneous and induced nonhuman primate models and describes relevant mouse models in the context of each pathogenetic mechanism.


Dynamics of polymerization in polyacrylamide gel (PAG) dosimeters: (II) modeling oxygen diffusion.
Oxygen contamination of a polyacrylamide gel (PAG) dosimeter can have a significant detrimental effect upon the performance characteristics of the gel as a dosimeter. Oxygen contamination can occur during preparation, but can also arise from the diffusion of atmospheric oxygen through vessel walls. Even 'trace' amounts of oxygen present in any gaseous space (usually nitrogen filled) between the surface of the PAG and the vessel seal can have a detectable effect. This paper describes a method used to quantify the detrimental effects of a range of oxygen concentrations upon the performance of the PAG. The results of diffusion studies for air and pure oxygen diffusing into the PAG over time are presented and coupled with a novel method of calculating oxygen concentrations in the PAG. Results obtained suggest that the diffusion is Fickian. The coefficient of diffusion D has been calculated to be (8+/-2) x 10(-6) cm2 s(-1) for oxygen diffusing into PAG stored at 4 degrees C, under the assumption that the diffusion mechanism is independent of the concentration of the diffusing species. In addition, a quantitative relation has been established between the transverse relaxation rate R2 of the PAG and the concentration of oxygen present. The implications of these findings for polymer gel dosimetry are discussed.


Effects of TAK-639, a novel topical C-type natriuretic peptide analog, on intraocular pressure and aqueous humor dynamics in mice.
Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness, and individuals with ocular hypertension are at risk to develop POAG. Currently, the only modifiable risk factor for glaucoma progression is lowering of intraocular pressure (IOP). A novel mechanism for lowering IOP involves activation of the type B natriuretic peptide receptor (NPR-B), the naturally occurring agonist of which is C-type natriuretic peptide (CNP). Being a cyclic peptide of 22 amino acids, CNP does not readily penetrate the cornea and its ocular hypotensive effect requires intraocular injection. TAK-639 is a synthetic, cornea-permeable, 9-amino acid CNP analog has been studied for the treatment of ocular hypertension and POAG. We assessed TAK-639 in a receptor binding profile and the effects of TAK-639 on NPR-B-mediated cyclic GMP production in cultured transformed human trabecular meshwork (TM) cells (GTM-3). We also evaluated the effects of topical ocular administration of TAK-639 on mouse IOP and aqueous humor dynamics. Among 89 non-natriuretic peptide receptors, transporters, and channels evaluated, TAK-639 at 10 μM displaced ligand binding by more than 50% to only two receptors: the type 2 angiotensin receptor (IC50 = 8.2 μM) and the cholecystokinin A receptor (IC50 = 25.8 μM). In vitro, TAK-639 selectively activates NPR-B (EC50 = 61 ± 11 nM; GTM-3 cells) relative to NPR-A (EC50 = 2179 ± 670 nM; 293T cells). In vivo, TAK-639 lowered mouse IOP by three mechanisms: increase in aqueous humor outflow facility (C), reduction in the aqueous humor formation rate (Fin), and reduction in episcleral venous pressure (Pe). The maximum mean IOP decreases from baseline were -12.1%, -21.0%, and -36.1% for 0.1%, 0.3%, and 0.6% doses of TAK-639, respectively. Maximum IOP-lowering effect was seen at 2 h, and the duration of action was >6 h. With TAK-639 0.6%, at 2 h post-dose, aqueous outflow facility (C) increased by 155.8%, Fin decreased by 41.0%, the uveoscleral outflow rate (Fu) decreased by 52.6%, and Pe decreased by 31.5% (all p < 0.05). No ocular adverse effects were observed. TAK-639 is an efficacious IOP-lowering agent, with a unique combination of mechanisms of action on both aqueous formation and aqueous outflow facility. Further study of this mechanism of treatment may optimize pharmacologic outcomes and provide disease management in patients with POAG and ocular hypertension.


Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe-Dnmts axis.
DNA hypermethylation is one of the most common epigenetic modifications in prostate cancer (PCa). Several studies have delineated sarcosine as a PCa oncometabolite that increases the migration of malignant prostate cells while decreasing their doubling time. Here, we show that incubation of prostate cells with sarcosine elicited the upregulation of sarcosine N-demethylation enzymes, sarcosine dehydrogenase and pipecolic acid oxidase. This process was accompanied by a considerable increase in the production of the major methyl-donor S-adenosylmethionine (SAMe), together with an elevation of cellular methylation potential. Global DNA methylation analyses revealed increases in methylated CpG islands in distinct prostate cell lines incubated with sarcosine, but not in cells of nonprostate origin. This phenomenon was further associated with marked upregulation of DNA methyltransferases (Dnmts). Epigenetic changes were recapitulated through blunting of Dnmts using the hypomethylating agent 5-azacytidine, which was able to inhibit sarcosine-induced migration of prostate cells. Moreover, spatial mapping revealed concomitant increases in sarcosine, SAMe and Dnmt1 in histologically confirmed malignant prostate tissue, but not in adjacent or nonmalignant tissue, which is in line with the obtained in vitro data. In summary, we show here for the first time that sarcosine acts as an epigenetic modifier of prostate cells and that this may contribute to its oncometabolic role.


Soybean hulls as an alternative feed for horses.
Soybean hulls have been successfully fed to ruminant animals as an economical substitute for hay. This feedstuff is a source of highly digestible fiber that does not contain starch. The purpose of this trial was to evaluate soybean hulls as a replacement fiber in horse diets. Four cecally cannulated Quarter Horse geldings, aged 6 to 10 yr and averaging 502 kg, were used in a 4 x 4 Latin square design with 21-d periods. Diets consisted of alfalfa/bromegrass hay (14.4% CP, 58.1% NDF, 39.1% ADF; DM basis) with the replacement of either 0, 25, 50, or 75% (as-fed basis) unpelleted soybean hulls (13.1% CP, 60.6% NDF, 43.7% ADF; DM basis). Diets were offered at 1.8% of BW (DM) daily and body weights were measured weekly. Cecal samples (90 min after feeding) and total fecal collections (3 d) were taken at the end of each treatment period. Fecal collection bags were emptied every 6 h and 10% of the total amount was frozen for later analysis. Total cecal VFA production increased linearly (P = 0.02) from 70 mM to 109 mM as proportions of soybean hulls in diets increased. Proportions of propionate increased linearly (P < 0.01) with means of 15.7, 18.0, 16.6, and 21.9 mol/100 mol total VFA for the 0, 25, 50, and 75% soybean hulls diets respectively. Proportions of butyrate decreased linearly (P < 0.01) from 5.3 to 3.9 mol/100 mol total VFA. The acetate:propionate ratio decreased linearly (P = 0.02) and cubically (P = 0.03) with means of 4.9, 4.2, 4.9, and 3.3. Apparent digestibility of DM (P = 0.95), OM (P = 0.70), NDF (P = 0.34), ADF (P = 0.31), cellulose (P = 0.93), and hemicellulose (P = 0.25) did not differ among treatments. Apparent digestibility of N decreased linearly (P < 0.01) as concentrations of soybean hulls increased in the diet, and this response was associated with increased cecal fermentation and microbial biomass production. Cecal pH decreased linearly (P = 0.01) from 7.00 to 6.45 as the level of soybean hulls increased, but there was no change (P = 0.68 for the linear effect) for cecal ammonia (mean concentration of 3.85 mM). Soybean hulls stimulate cecal fermentation and are a suitable replacement for hay in equine diets.


Candida albicans aspects of novel silane system-coated titanium and zirconia implant surfaces.
The aim of the present study was to evaluate the effect of novel silane system coatings on zirconia and titanium implant surfaces and the attachment of the fungal pathogen Candida albicans. Titanium and zirconia specimens were silica-coated and silanized either with a commercial silane primer (RelyX Ceramic Primer™, 3M ESPE) or a novel silane system primer. The novel silane system primer was a blend of 1.0 vol% 3-acryloxypropyltrimethoxysilane and 0.3 vol% bis-1,2-(triethoxysilyl)ethane diluted in acidified ethanol-water solvent. The surface roughness (Ra ), the surface free energy and the chemical composition of substrate surfaces after treatments were evaluated. C. albcans biofilms were developed on silica-coated + silanized surfaces during 48 h of incubation time. Colony forming units (CFU) and real-time PCR (RT-PCR) quantified the cells on the material surfaces. Statistical analyses were carried out by 1-way ANOVA, Tukey post hoc and Games Howell post hoc test at 5% significance level (p). On zirconia and titanium surfaces, the Ra and the chemical composition of the specimens were equal (P < 0.05). The surface free energy was decreased on titanium specimens and increased on zirconia specimen after silanization. CFU of C. albicans was significantly lower on zirconia coated with RelyX Ceramic Primer™, (P < 0.001) and on titanium coated with both silanes (P = 0.002). RT-PCR revealed no differences between the mean quantities of C. albicans (P ≥ 0.067). Silica-coating and silanization had modified the titanium and zirconia surfaces significantly. Both the control and experimental silane primers might inhibit the biofilm formation of C. albicans.


Gastric emptying measurement of liquid nutrients using the (13)C-octanoate breath test in critically ill patients: a comparison with scintigraphy.
Scintigraphy is considered the most accurate technique for the measurement of gastric emptying (GE) but, for patients in the intensive care unit, it is technically demanding, involves radiation and can interfere with care. The (13)C-octanoate breath test ((13)C-OBT) is a simple, non-invasive technique that does not involve radiation exposure. To evaluate the performance of the (13)C-OBT in the assessment of GE in critically ill patients. The GE was assessed in 33 mechanically ventilated patients (23 M; 54.3 ± 3.0 yrs; APACHE II: 22.0 ± 1.1). Following test meal administration (100 ml Ensure(®)), concurrent scintigraphic measurement and breath samples ((13)C-OBT) were collected over 4 h. Scintigraphic meal retention was determined and the gastric emptying coefficient (GEC) and half emptying time [t50(BT)] were calculated for the (13)C-OBT. Delayed GE was defined as meal retention >13 % at 180 min. Delayed GE was identified in 27/33 patients. Meal retention correlated modestly with t50(BT) (r = 0.55-0.66; P < 0.001) and well with GEC (r = -0.63 to -0.74; P < 0.0001). The strength of agreement between the two techniques was highest between GEC and retention at 120 min. The best cut-off GEC for defining delayed GE was 3.25 (AUC = 0.75; 95 % CI = 0.52-0.99; P = 0.05), with 89 % sensitivity and 67 % specificity to detect delayed GE. The GE was delayed in all (23/23) patients with feed intolerance (GRV > 250 ml) on scintigraphy and 91 % (21/23) patients on (13)C-OBT. In critical illness, there was a correlation between (13)C-OBT and gastric scintigraphy, with GEC performing as a better and more sensitive marker of detecting delayed GE than t50. However the relatively wide 95 % confidence intervals suggest that (13)C-OBT is more suitable as a technique to assess GE in a group setting for research studies rather than for individual patients in clinical practice.


Analysis of the promoter elements necessary for IL-4 and anti-CD40 antibody induction of murine Fc epsilon RII (CD23): comparison with the germline epsilon promoter.
IL-4 and CD40 ligand stimulate transcription of CD23 (Fc epsilonRII) in B cells and are necessary for the expression of germline epsilon mRNA and production of IgE. Because in vivo studies have shown that the Fc epsilonRII is involved in the regulation of IgE, a study was initiated to compare how IL-4 and engagement of CD40 up-regulate the Fc epsilonRII and epsilon genes. Herein, we describe the preparation of a series of linker-scanning mutants that cover the IL-4 response region in the murine Fc epsilonRII promoter, and their function when transfected into M12.4.5 and M12.4.1 B lymphoma cell lines. Several discrete elements were found to be necessary for IL-4 induction of the Fc epsilonRII gene, some of which have homology with the binding sites of known transcription factors, including NF-IL-4 and NF-kappaB. In contrast, the response element for anti-CD40 (plus IL-4) mapped to a single discrete sequence, a NF-kappaB-like site. Aligning the Fc epsilonRII and germline epsilon promoters in the region that is highly conserved between the human and mouse homologues of both genes reveals a high degree of identity, particularly within discrete clusters. Comparing the function of linker-scanning mutants of the Fc epsilonRII promoter with a similar report for germline epsilon shows that both genes require at least two homologous and similarly located DNA elements in their promoters for a full IL-4 induction. Moreover, the similar response of Fc epsilonRII and epsilon promoter-driven chloramphenicol acetyl transferase plasmids to several cytokines and other agents suggests that the two proximal promoter regions are activated by a similar cassette of factors.


Design and development of a nutritional assessment application for smartphones and tablets with Android OS.
To design and develop a nutritional application for smartphones and tablets with Android operating system for using to in- and outpatients that need a nutritional assessment. To check the validity of the results of such software. The application was compiled for version 2.1 of the Android operating system from Google. A cohort of 30 patients was included for evaluating the reliability of the application. The calculations were performed by staff of the Nutrition Unit of the Complexo Hospitalario Universitario de Vigo, manually and through e-Nutrimet software on a smartphone and a tablet. Concordance was absolute between results of different methods obtained using e-Nutrimet on a smartphone and a tablet (Fleiss index κ= 1). The same level of concordance was obtained by comparing handmade and e-Nutrimet made results. The degree of correlation is good, and it would be extended to all healthcare staff who wants to determine whether a patient has malnutrition, or not. The nutritional assessment software e-Nutrimet does not replace healthcare staff in any case, but could be an important aid in assessing patients who may be in risk of malnutrition, saving time of evaluation.


Spousal loss and cognitive function in later life: a 25-year follow-up in the AGES-Reykjavik study.
The aim of this study was to investigate the associations between loss of a life partner and the development of dementia and decline in cognitive function in later life. We used an Icelandic cohort of 4,370 participants in the Age, Gene/Environment Susceptibility-Reykjavik Study who were living as married in 1978 (born in 1907-1935) and were either still married (unexposed cohort) or widowed (exposed cohort) at follow-up (in 2002-2006). We ascertained history of marital status and spouse's death by record linkage to the Registry of the Total Population, Statistics Iceland. The outcome measures were as follows: 1) dementia and mild cognitive impairment; and 2) memory, speed of processing, and executive function. During the observation period, 3,007 individuals remained married and 1,363 lost a spouse through death. We did not find any significant associations between loss of a spouse and our outcome variables, except that widowed women had poorer executive function (mean = -0.08) during the first 2 years after their husbands' deaths compared with still-married women (mean = 0.09). Our findings do not support the notion that the risk of dementia is increased following the loss of a spouse, yet women demonstrate a seemingly temporary decline in executive function following the death of a partner.


Resonant infrared transmission and effective medium response of subwavelength H-fractal apertures.
The transmission through periodic arrays of subwavelength H-fractal apertures in a gold film at infrared wavelengths is investigated numerically. H-fractal apertures support subwavelength cut-off resonances that are hybridized with surface plasmons along the sidewalls of the aperture. Enhanced transmission occurs at wavelengths that are about ten times the aperture side length. The highly subwavelength size scale of the H-fractal enables an effective medium parameter description for the aperture array, which reveals a lossy plasma permittivity and a diamagnetic permeability.


Cardiovascular disease: a historic perspective.
Cardiovascular disease (CVD) is the leading cause of death and disability in the United States and in most industrialized nations. Major breakthroughs to modern day cardiovascular/lipid research have been attributed to the findings of the Framingham Heart Study and Gofman and colleagues who made associations between lipoprotein levels (LDL, VLDL and HDL) and CVD. Unfortunately, half of all CVD patients have none of the established coronary risk factors (hypertension, hypercholesterolemia, cigarette smoking, diabetes mellitus, obesity) and new strategies for identifying patients need be considered. Although there remains little disagreement regarding the necessity to lower elevated plasma cholesterol levels, there remains much controversy regarding appropriate dietary means of accomplish this goal. The National Cholesterol Education Program (1993) proposed a dietary reduction (Step I and Step II diets) to the percent saturated fat and cholesterol consumed by at-risk patients. Many currently question about the effectiveness of these diets and an alternative diet, replacing saturated fats by monounsaturated fats (olive oil), has attracted recent attention. While diet modification is considered the foundation of primary treatment, other interventions are frequently required. Although early drug trials demonstrated that agents such as nicotinic acid, clofibrate, gemfibrozil, bile acid-binding resins generally slowed progression of atherosclerotic lesions, lowered plasma cholesterol levels and decreased mortality from CVD, the greatest advance to current drug therapy involved the discovery of the "statins" (HMG-CoA reductase inhibitors). In the current work, mechanisms for vascular dysfunction resulting in myocardial ischemia were explored and potential nutritional (dietary) and pharmacologic interventions were reviewed.


The Promise of Proteomics for the Study of ADP-Ribosylation.
ADP-ribosylation is a post-translational modification where single units (mono-ADP-ribosylation) or polymeric chains (poly-ADP-ribosylation) of ADP-ribose are conjugated to proteins by ADP-ribosyltransferases. This post-translational modification and the ADP-ribosyltransferases (also known as PARPs) responsible for its synthesis have been found to play a role in nearly all major cellular processes, including DNA repair, transcription, translation, cell signaling, and cell death. Furthermore, dysregulation of ADP-ribosylation has been linked to diseases including cancers, diabetes, neurodegenerative disorders, and heart failure, leading to the development of therapeutic PARP inhibitors, many of which are currently in clinical trials. The study of this therapeutically important modification has recently been bolstered by the application of mass spectrometry-based proteomics, arguably the most powerful tool for the unbiased analysis of protein modifications. Unfortunately, progress has been hampered by the inherent challenges that stem from the physicochemical properties of ADP-ribose, which as a post-translational modification is highly charged, heterogeneous (linear or branched polymers, as well as monomers), labile, and found on a wide range of amino acid acceptors. In this Perspective, we discuss the progress that has been made in addressing these challenges, including the recent breakthroughs in proteomics techniques to identify ADP-ribosylation sites, and future developments to provide a proteome-wide view of the many cellular processes regulated by ADP-ribosylation.


Spread of pseudorabies virus among breeding swine in quarantined herds.
In theory, pseudorabies virus (PRV) may be eliminated from any size of breeding herd by phased test and removal if replacement gilts are not infected with PRV, culling decisions are partially based on PRV status, and the cull rate is higher than the incidence rate of PRV. Annual cull rates are commonly at least 50%, but little information exists on the incidence of PRV within enzootically infected swine herds. The purpose of this study was to develop a method by which spread of PRV could be detected among breeding swine within enzootically infected herds and to determine the incidence of PRV infection in these herds. Data were collected from 17 herds that were quarantined for PRV and ranged in size from 120 to 1,100 sows. At each herd, within the first 5 days of introduction, a group of approximately 30 replacement gilts was identified, vaccinated with a glycoprotein X-deleted PRV vaccine, and blood sample was collected. The owner of 1 herd had a nonvaccinated breeding herd and elected to leave incoming gilts nonvaccinated. After vaccination, blood samples were collected every 1 to 2 months for an average of 13.6 months. Serum samples from vaccinated gilts were tested for antiglycoprotein X antibodies by a specific differential ELISA. Samples from nonvaccinated gilts were evaluated by serum neutralization test. Product-limit method was used to estimate the probability of not becoming infected with PRV. Spread was detected in 7 of 8 herds that had more than 400 sows and in 2 of 9 herds that had less than 400 sows.(ABSTRACT TRUNCATED AT 250 WORDS)


Appraising and applying evidence about a diagnostic test during a performance-based assessment.
The practice of Evidence-based Medicine requires that clinicians assess the validity of published research and then apply the results to patient care. We wanted to assess whether our soon-to-graduate medical students could appraise and apply research about a diagnostic test within a clinical context and to compare our students with peers trained at other institutions. 4th year medical students who previously had demonstrated competency at probability revision and just starting first-year Internal Medicine residents were used for this research. Following an encounter with a simulated patient, subjects critically appraised a paper about an applicable diagnostic test and revised the patient's pretest probability given the test result. The medical students and residents demonstrated similar skills at critical appraisal, correctly answering 4.7 and 4.9, respectively, of 6 questions (p = 0.67). Only one out of 28 (3%) medical students and none of the 15 residents were able to correctly complete the probability revision task (p = 1.00). This study found that most students completing medical school are able to appraise an article about a diagnostic test but few are able to apply the information from the article to a patient. These findings raise questions about the clinical usefulness of the EBM skills possessed by graduating medical students within the area of diagnostic testing.


Peptide-siRNA nanocomplexes targeting NF-κB subunit p65 suppress nascent experimental arthritis.
The NF-κB signaling pathway is implicated in various inflammatory diseases, including rheumatoid arthritis (RA); therefore, inhibition of this pathway has the potential to ameliorate an array of inflammatory diseases. Given that NF-κB signaling is critical for many immune cell functions, systemic blockade of this pathway may lead to detrimental side effects. siRNAs coupled with a safe and effective delivery nanoplatform may afford the specificity lacking in systemic administration of small-molecule inhibitors. Here we demonstrated that a melittin-derived cationic amphipathic peptide combined with siRNA targeting the p65 subunit of NF-κB (p5RHH-p65) noncovalently self-assemble into stable nanocomplexes that home to the inflamed joints in a murine model of RA. Specifically, administration of p5RHH-p65 siRNA nanocomplexes abrogated inflammatory cytokine expression and cellular influx into the joints, protected against bone erosions, and preserved cartilage integrity. The p5RHH-p65 siRNA nanocomplexes potently suppressed early inflammatory arthritis without affecting p65 expression in off-target organs or eliciting a humoral response after serial injections. These data suggest that this self-assembling, largely nontoxic platform may have broad utility for the specific delivery of siRNA to target and limit inflammatory processes for the treatment of a variety of diseases.


Decontamination solutions for polychlorinated biphenyls (PCBs) in raw fish oils from environmentally contaminated sea fishes.
Fish oil has been identified as one of the most important contributors to the levels of polychlorinated biphenyls (PCBs) in food and feed products. In this study, PCB adsorption from fish oil onto activated carbon (AC), other sustainable adsorbents (mussel shell and wood waste ashes) and organic solvent such as ethanol were compared and optimized. Regarding to adsorbents, PCBs were extracted from fish oil by a 2.0% adsorbent material dose, during 6.0 h at 25 °C. Solvent extraction was carried out using 2 × 5.0 mL ethanol by manually stirring for 3.0 min, and then by Ultrasound-Assisted Solvent Extraction (UASE) for 5.0 min. The results showed that removal rates obtained by using adsorbent materials ranged from 0.0 to 10% for marker PCBs, from 0.0 to 37% for mono-ortho-PCBs, from 0.0 to 74% for PCB11 and from 0.0 to 95% for non-ortho-PCBs. Regarding to solvent extraction, ethanol was used by manually stirring and then by Ultrasound-Assisted Solvent Extraction (UASE). The samples were then centrifuged (2000 rpm/10 min) and the alcoholic phase was removed. With this method, removal efficiencies were much better (85-116%); nevertheless, high eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) removal rates (70-78 and 71-79%, respectively) were detected. We can conclude that adsorption with adsorbents depends on the geometry of PCB congeners, as well as both type of adsorption material and their origin, and that several sorption cycles are needed. Adsorption with ethanol could be the most effective methodology but nutritional quality was impaired, what makes necessary to look for other not so polar removal solvents.


How valid are projections of the future prevalence of diabetes? Rapid reviews of prevalence-based and Markov chain models and comparisons of different models' projections for England.
To examine validity of prevalence-based models giving projections of prevalence of diabetes in adults, in England and the UK, and of Markov chain models giving estimates of economic impacts of interventions to prevent type 2 diabetes (T2D). Rapid reviews of both types of models. Estimation of the future prevalence of T2D in England by Markov chain models; and from the trend in the prevalence of diabetes, as reported in the Quality and Outcomes Framework (QOF), estimated by ordinary least squares regression analysis. Adult population in England and UK. Prevalence of T2D in England and UK in 2025. The prevalence-based models reviewed use sample estimates of past prevalence rates by age and sex and projected population changes. Three most recent models, including that of Public Health England (PHE), neither take account of increases in obesity, nor report Confidence Intervals (CIs). The Markov chain models reviewed use transition probabilities between states of risk and death, estimated from various sources. None of their accounts give the full matrix of transition probabilities, and only a minority report tests of validation. Their primary focus is on estimating the ratio of costs to benefits of preventive interventions in those with hyperglycaemia, only one reported estimates of those developing T2D in the absence of a preventive intervention in the general population.Projections of the prevalence of T2D in England in 2025 were (in millions) by PHE, 3.95; from the QOF trend, 4.91 and by two Markov chain models, based on our review, 5.64 and 9.07. To inform national policies on preventing T2D, governments need validated models, designed to use available data, which estimate the scale of incidence of T2D and survival in the general population, with and without preventive interventions.


Evolution of lbx spinal cord expression and function.
Ladybird homeobox (Lbx) transcription factors have crucial functions in muscle and nervous system development in many animals. Amniotes have two Lbx genes, but only Lbx1 is expressed in spinal cord. In contrast, teleosts have three lbx genes and we show here that zebrafish lbx1a, lbx1b, and lbx2 are expressed by distinct spinal cell types, and that lbx1a is expressed in dI4, dI5, and dI6 interneurons, as in amniotes. Our data examining lbx expression in Scyliorhinus canicula and Xenopus tropicalis suggest that the spinal interneuron expression of zebrafish lbx1a is ancestral, whereas lbx1b has acquired a new expression pattern in spinal cord progenitor cells. lbx2 spinal expression was probably acquired in the ray-finned lineage, as this gene is not expressed in the spinal cords of either amniotes or S. canicula. We also show that the spinal function of zebrafish lbx1a is conserved with mouse Lbx1. In zebrafish lbx1a mutants, there is a reduction in the number of inhibitory spinal interneurons and an increase in the number of excitatory spinal interneurons, similar to mouse Lbx1 mutants. Interestingly, the number of inhibitory spinal interneurons is also reduced in lbx1b mutants, although in this case the number of excitatory interneurons is not increased. lbx1a;lbx1b double mutants have a similar spinal interneuron phenotype to lbx1a single mutants. Taken together these data suggest that lbx1b and lbx1a may be required in succession for correct specification of dI4 and dI6 spinal interneurons, although only lbx1a is required for suppression of excitatory fates in these cells.


Genistein attenuates oxidative stress and neuronal damage following transient global cerebral ischemia in rat hippocampus.
Oxidative stress is believed to contribute to neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. The present study was undertaken to evaluate the possible antioxidant neuroprotective effect of genistein against neuronal death in hippocampal CA1 neurons following transient global cerebral ischemia in the rat. Transient global cerebral ischemia was induced in male Sprague-Dawley rats by four-vessel-occlusion for 10min. At various times of reperfusion, the histopathological changes and the levels of mitochondria-generated reactive oxygen species (ROS), malondialdehyde (MDA), cytosolic cytochrome c and caspase-3 activity in hippocampus were measured. We found extensive neuronal death in the CA1 region at day 5 after I/R. The ischemic changes were preceded by increases in ROS generation and MDA concentration and followed by increased cytosolic cytochrome c, and subsequently caspase-3 activation and apoptosis. Treatment with genistein (15mg/kg, i.p.) significantly attenuated ischemia-induced neuronal death. Genistein administration also decreased ROS generation, MDA concentration and the apoptotic indices. These results suggest that genistein protects neurons from transient global cerebral I/R injury in rat hippocampus by attenuating oxidative stress, lipid peroxidation and the signaling cascade leading to apoptotic cell death.


Impact of biological control agents on fusaric acid secreted from Fusarium oxysporum f. sp. gladioli (Massey) Snyder and Hansen in Gladiolus grandiflorus corms.
Fusaric acid (FA) (5-n-butylpuridine 2-carboxyl acid), a highly toxic secondary metabolite produced by Fusarium oxysporum strains, plays a significant role in disease development. The abilities of three F. oxysporum f. sp. gladioli (Massey) Snyder and Hansen isolates (G010; 649-91; and 160-57) to produce FA in infected Gladiolus corm tissues was evaluated in vitro in relation to the presence of two biological control agents, Trichoderma harzianum T22, and Aneurinobacillus migulanus. Pathogenicity tests were used to differentiate between the abilities of the F. oxysporum strains to secrete FA. FA was identified using LC/MS and quantified using HPLC. Isolate G010 was significantly more virulent (P < 0.01) on Gladiolus grandiflorus corms; it secretes 1.8 μM FA/g fresh weight corm into inoculated Gladiolus. Moreover, G010 was the only isolate that produced FA among the three examined isolates. There was a correlation between the corm lesion area and the FA secretion ability of F. oxysporum f. sp. gladioli (P < 0.001; r (2) = 0.96). No FA was detected in PDA cultures of F.oxysporum f. sp. gladioli isolates. The presence of T. harzianum T22 appeared to prevent FA secretion into the corms. In the presence of A. migulanus, however, the amount of FA secreted into the corm tissues increased. These results support the use of T. harzianum as an effective biological control agent against F. oxysporum f. sp. gladioli.


Potential Medication-Related Problems in Older Breast, Colon, and Lung Cancer Patients in the United States.
Background: Older adults are often exposed to multiple medications, some of which could be inappropriate or have the potential to interact with each other. Older cancer patients may be at increased risk for medication-related problems due to exposure to cancer-directed treatment.Methods: We described patterns of potentially inappropriate medication (PIM) use and potential drug-chemotherapy interactions among adults age 66+ years diagnosed with stage I-III breast, stage II-III colon, and stage I to II lung cancer. Within the Surveillance, Epidemiology, and End Results-Medicare database, patients had to have Medicare Part D coverage with 1+ prescription in the diagnosis month and Medicare Parts A/B coverage in the prior 12 months. We estimated monthly prevalence of any and cancer-related PIM from 6 months pre- to 23 months postcancer diagnosis and 12-month period prevalence of potential drug-chemotherapy interactions.Results: Overall, 19,318 breast, 7,283 colon, and 7,237 lung cancer patients were evaluated. Monthly PIM prevalence was stable prediagnosis (37%-40%), but increased in the year following a colon or lung cancer diagnosis, and decreased following a breast cancer diagnosis. Changes in PIM prevalence were driven primarily by cancer-related PIM in patients on chemotherapy. Potential drug-chemotherapy interactions were observed in all cohorts, with prevalent interactions involving hydrochlorothiazide, warfarin, and proton-pump inhibitors.Conclusions: There was a high burden of potential medication-related problems among older cancer patients; future research to evaluate outcomes of these exposures is warranted.Impact: Older adults diagnosed with cancer have unique medication management needs. Thus, pharmacy specialists should be integrated into multidisciplinary teams caring for these patients. Cancer Epidemiol Biomarkers Prev; 27(1); 41-49. ©2017 AACR.


Anti-hepatocarcinoma effects of 5-fluorouracil encapsulated by galactosylceramide liposomes in vivo and in vitro.
To study the anti-hepatocarcinoma effects of 5-fluorouracil (5-Fu) encapsulated by galactosylceramide liposomes (5-Fu-GCL) in vivo and in vitro. Tumor-bearing animal model and HepA cell line were respectively adopted to evaluate the anti-tumor effects of 5-Fu-GCL in vivo and in vitro. Tumor cell growth inhibition effects of 5-Fu-GCL in vitro were assessed by cell viability assay and MTT assay. In vivo experiment, the inhibitory effects on tumor growth were evaluated by tumor inhibition rate and animal survival days. High performance liquid chromatography was used to detect the concentration-time course of 5-Fu-GCL in intracellular fluid in vitro and the distribution of 5-Fu-GCL in liver tumor tissues in vivo. Apoptosis and cell cycle of tumor cells were demonstrated by flow cytometry. In vitro experiment, 5-Fu-GCL (6.25-100 micromol/L) and free 5-Fu significantly inhibited HepA cell growth. Furthermore, IC50 of 5-Fu-GCL (34.5 micromol/L) was lower than that of free 5-Fu (51.2 micromol/L). In vivo experiment, 5-Fu-GCL (20, 40, 80 mg/kg) significantly suppressed the tumor growth in HepA bearing mice model. Compared with free 5-Fu, the area under curve of 5-Fu-GCL in intracellular fluid increased 2.6 times. Similarly, the distribution of 5-Fu-GCL in liver tumor tissues was significantly higher than that of free 5-Fu. After being treated with 5-Fu-GCL, the apoptotic rate and the proportion of HepA cells in the S phase increased, while the proportion in the G0/G1 and G2/M phases decreased. 5-Fu-GCL appears to have anti-hepato-carcinoma effects and its drug action is better than free 5-Fu. Its mechanism is partly related to increased drug concentrations in intracellular fluid and liver tumor tissues, enhanced tumor cell apoptotic rate and arrest of cell cycle in S phase.


Intrinsic CanMEDS Competencies Expected of Medical Students During Emergency Medicine Core Rotation: A Needs Assessment.
Objectives There are few high-quality free open-access medical (FOAM) education resources to guide medical students in the development of key non-medical expert skills and competencies during their emergency medicine (EM) clerkship core rotation. In our endeavor to develop a novel online educational EM curriculum for medical students, a needs assessment is required to effectively address needs specifically focused on aptitudes that are deemed to be imperative by educators in the EM academia. Methods An online needs assessment survey was developed and shared with residents, staff, nurses, and program/clerkship directors of Canadian emergency medicine programs by email correspondence and embedding the form on CanadiEM.org. The survey consisted of twelve proposed topics for a potential EM curriculum, which were graded on a five-point Likert scale. Free-typed responses for additional topics were also solicited from participants. Results Over the course of four weeks, 84 participants responded to the survey. Participants outside of North American were excluded (n=10). Most participants were North American staff physicians (n=52), which included residency program directors (n=10) and clerkship directors (n=6), followed by residents (n=14), and nurses (n=8). All 12 topics proposed by the authors were considered important for inclusion in an EM curriculum. Nine additional topics were identified from typed free-text responses. Top ranking topics included: how to present a case to an EM staff or resident, how to chart patient encounters, and how to effectively communicate with nurses and other healthcare professionals. Conclusions This online needs assessment analysis revealed a total of 21 topics that were deemed to be relevant to the development of an online curriculum to foster the development of core competencies of medical students during their EM core rotation.


Aerodynamic characteristics in upper airways among orthodontic patients and its association with adenoid nasopharyngeal ratios in lateral cephalograms.
Adenoid hypertrophy among orthodontic patients may be detected in lateral cephalograms. The study investigates the aerodynamic characteristics within the upper airway (UA) by means of computational fluid dynamics (CFD) simulation. Furthermore, airflow features are compared between subgroups according to the adenoidal nasopharyngeal (AN) ratios. This retrospective study included thirty-five patients aged 9-15 years having both lateral cephalogram and cone beam computed tomography (CBCT) imaging that covered the UA region. The cases were divided into two subgroups according to the AN ratios measured on the lateral cephalograms: Group 1 with an AN ratio < 0.6 and Group 2 with an AN ratio ≥ 0.6. Based on the CBCT images, segmented UA models were created and the aerodynamic characteristics at inspiration and expiration were simulated by the CFD method for the two groups. The studied aerodynamic parameters were pressure drop (ΔP), maximum midsagittal velocity (Vms), maximum wall shear stress (Pws), and minimum wall static pressure (Pw). The maximum Vms exhibits nearly 30% increases in Group 2 at both inspiration (p = 0.013) and expiration (p = 0.045) compared to Group 1. For the other aerodynamic parameters such as ΔP, the maximum Pws, and minimum Pw, no significant difference is found between the two groups. The maximum Vms seems to be the most sensitive aerodynamic parameter for the groups of cases. An AN ratio of more than 0.6 measured on a lateral cephalogram may associate with a noticeably increased maximum Vms, which could assist clinicians in estimating the airflow features in the UA.


Letter and semantic fluency in older adults: effects of mild depressive symptoms and age-stratified normative data.
Depression induced cognitive impairment, also referred to as the dementia syndrome of depression or pseudodementia, has been well characterized, yet the extent to which the more common mild depressive symptoms influence cognition has not been well studied. We sought to identify the influence of mild depressive symptoms on verbal fluency performance in a large sample of healthy community dwelling older adults. Letter and semantic fluency testing was conducted on 188 participants (ages 60-92 years) with no known history of neurologic or psychiatric disease. Depressive symptoms were assessed with the Geriatric Depression Scale (GDS). A total of 39 subjects obtained GDS scores consistent with mild depressive symptoms (GDS=10-19), and 149 subjects were identified as not depressed (GDS<10). ANOVA indicated that subjects with mild depressive symptoms performed significantly worse than normal controls on letter fluency (p<.05), but there was no significant difference between the groups on semantic fluency. Analysis of the nondepressed group stratified into young-old, middle-old, and oldest-old revealed a significant decline in semantic (p<.001) but not letter fluency with age. The nondepressed young-old showed the expected advantage for word list generation to semantic as compared to letter categories, yet this pattern was reversed in the older age groups, where letter fluency scores exceeded semantic fluency scores. Our results suggest that the presence of even mild depressive symptoms may confound using letter versus category discrepancies in the differential diagnosis of dementia. Further, our findings suggest that the commonly used strategy of examining letter-semantic fluency discrepancies may not be relevant for individuals of advanced age. Age-stratified normative data for fluency testing in older adults is also provided.


Registration for deceased organ and tissue donation among Ontario immigrants: a population-based cross-sectional study.
Canada has low rates of deceased organ and tissue donation. Immigrants to Canada may differ in their registered support for deceased organ donation based on their country of origin. We used linked administrative databases in Ontario (about 11 million residents aged ≥ 16 yr) to study the proportion of immigrants and long-term residents registered for deceased organ and tissue donation as of October 2013. We used modified Poisson regression to identify and quantify predictors of donor registration. Compared with long-term residents (n = 9 244 570), immigrants (n = 1 947 646) were much less likely to register for deceased organ and tissue donation (11.9% v. 26.5%). Immigrants from the United States, Australia and New Zealand had the highest registration rate (40.0%), whereas immigrants with the lowest registration rates were from Eastern Europe and Central Asia (9.4%), East Asia and Pacific (8.4%) and sub-Saharan Africa (7.9%). The largest numbers of unregistered immigrants were from India (n = 202 548), China (n = 186 678) and the Philippines (n = 125 686). Characteristics among the immigrant population associated with a higher likelihood of registration included economic immigrant status, living in a rural area (population < 10 000), living in an area with a lower ethnic concentration, less material deprivation, a higher education, ability to speak English and French, and more years residing in Canada. Immigrants in Ontario were less likely to register for deceased organ and tissue donation than long-term residents. There is a need to better understand reasons for lower registration rates among Canadian immigrants and to create culture-sensitive materials to build support for deceased organ and tissue donation.


Dental implants inserted in native bone: Cases series analyses.
The concept of osseointegration, i.e., the direct anchorage of endosseous implants made of commercially pure or titanium alloy to the bone caused a breakthrough in oral rehabilitation. The identification of factors for long-term survival and success rate are the main goal of the recent literature. Several variables can influence the final result, and in general they are grouped in surgery-, host-, implant-, and occlusion-related factors. A retrospective analysis on a large series of dental implants was performed to detect those variables influencing the clinical outcome. In the period between January 2007 and December 2009, 157 patients were operated. A total of 429 implants were inserted. Dental implants are reliable devices to be used in oral rehabilitation. Globally, very few implants were lost at the end of the follow-up period. Slight but significant differences existed among different implants types with regard to peri-implant bone resorption. A better clinical outcome was revealed for Sweden and Martina global implant.


Early feeding of an energy dense diet during acute shigellosis enhances growth in malnourished children.
In a controlled clinical trial, we examined the effect of the short-term feeding of an energy-dense milk cereal formula in malnourished children with clinically severe dysentery due to acute shigellosis. Seventy-five malnourished children, aged 12-48 mo, passing blood or blood with mucous in the stool for < or = 96 h, were offered a hospital diet. In addition, study children (n = 36) were offered a milk-cereal formula with an energy of 5 kJ/g (an 11% protein diet); similarly, control children (n = 39) were offered a milk-cereal formula with an energy content of 2.5 kJ/g (an 11% protein diet). Patients were admitted to the metabolic ward of the Clinical Research and Service Centre, Dhaka, at the International Centre for Diarrhoeal Disease Research, Bangladesh. Patients were studied for 10 hospital days and were then followed up at home after 30 d. After 10 d of dietary intervention, children in the study group had a significantly greater increase vs. controls in weight-for-age (6 vs. 3%, P < 0.001) and in weight-for-height (7 vs. 3%, P < 0.001). Serum prealbumin concentrations were significantly higher (study vs. control) after 5 d (0.214 vs. 0.170 g/L, P = 0.01) and after 10 d (0.244 vs. 0.193 g/L, P = 0.006) of the study. Greater weight-for-age was sustained at home 1 mo after discharge (8 vs. 5%, P = 0.005) from the hospital. Similarly, higher weight-for-height was sustained 1 mo after discharge (8 vs. 5%, P = 0.01). During their stay at home, there was no dietary intervention. The results of this study suggest that short-term feeding of an energy-dense diet enhances growth in malnourished children with acute dysentery due to shigellosis.


Novel strategy to implement active-space coupled-cluster methods.
A new approach is presented for the efficient implementation of coupled-cluster (CC) methods including higher excitations based on a molecular orbital space partitioned into active and inactive orbitals. In the new framework, the string representation of amplitudes and intermediates is used as long as it is beneficial, but the contractions are evaluated as matrix products. Using a new diagrammatic technique, the CC equations are represented in a compact form due to the string notations we introduced. As an application of these ideas, a new automated implementation of the single-reference-based multi-reference CC equations is presented for arbitrary excitation levels. The new program can be considered as an improvement over the previous implementations in many respects; e.g., diagram contributions are evaluated by efficient vectorized subroutines. Timings for test calculations for various complete active-space problems are presented. As an application of the new code, the weak interactions in the Be dimer were studied.


[Characteristics of energy metabolism in the tissues of lake frogs and certain reptiles during prolonged deep hypothermia].
A week hypothermia (2-4 degrees C) does not cause a considerable decrease in content of glycogen in the liver, muscles, brain tissues of Lacerta strigata, Natrix tessellata and Rana ridibunda. In Eremias arguta pangolins the level of glycogen in the liver and muscles under these conditions is twice as low. Prolongation of hypothermia till three weeks causes a 4-fold decrease in the polysaccharide level in the liver of Eremias arguta and Lacerta strigata. The content of nonesterified fatty acids in blood under hypothermia (especially of three-week one) considerably exceeds the normal level. The content of lactic acid in tissues is two-three times as high under prolonged hypothermia, in the reptile muscles creatine phosphate accumulates in high amounts.


Incorporating sequence quality data into alignment improves DNA read mapping.
New DNA sequencing technologies have achieved breakthroughs in throughput, at the expense of higher error rates. The primary way of interpreting biological sequences is via alignment, but standard alignment methods assume the sequences are accurate. Here, we describe how to incorporate the per-base error probabilities reported by sequencers into alignment. Unlike existing tools for DNA read mapping, our method models both sequencer errors and real sequence differences. This approach consistently improves mapping accuracy, even when the rate of real sequence difference is only 0.2%. Furthermore, when mapping Drosophila melanogaster reads to the Drosophila simulans genome, it increased the amount of correctly mapped reads from 49 to 66%. This approach enables more effective use of DNA reads from organisms that lack reference genomes, are extinct or are highly polymorphic.


[The IGF system: summary and recent data].
We are entitled to state that our knowledge about the IGF system has literally exploded in the last years. Having been considered for some time merely as trophic and mitogenic factors, the IGFs now appear as molecules essential for the differentiation of many cell types, and even more so, as powerful protective agents for the nervous and the cardiovascular systems. However, these properties so beneficial in normal physiological conditions, are subverted by the cancerous cells who use them to extend their life span and resist therapy. The IGFs did not live up to expectations in the treatment of diabetes; however, today their capacity to improve the condition of patients suffering from severe neurological, renal or muscle diseases is tested. The IGF system might also be targetted by the anticancer treatments. In the following paper we have briefly summarized our knowledge on the IGF system, and presented in more detail the recent data.


Species-directed therapy for leishmaniasis in returning travellers: a comprehensive guide.
Leishmaniasis is increasingly reported among travellers. Leishmania species vary in sensitivity to available therapies. Fast and reliable molecular techniques have made species-directed treatment feasible. Many treatment trials have been designed poorly, thus developing evidence-based guidelines for species-directed treatment is difficult. Published guidelines on leishmaniasis in travellers do not aim to be comprehensive or do not quantify overall treatment success for available therapies. We aimed at providing comprehensive species-directed treatment guidelines. English literature was searched using PubMed. Trials and observational studies were included if all cases were parasitologically confirmed, the Leishmania species was known, clear clinical end-points and time points for evaluation of treatment success were defined, duration of follow-up was adequate and loss to follow-up was acceptable. The proportion of successful treatment responses was pooled using mixed effects methods to estimate the efficacy of specific therapies. Final ranking of treatment options was done by an expert panel based on pooled efficacy estimates and practical considerations. 168 studies were included, with 287 treatment arms. Based on Leishmania species, symptoms and geography, 25 clinical categories were defined and therapy options ranked. In 12/25 categories, proposed treatment agreed with highest efficacy data from literature. For 5/25 categories no literature was found, and in 8/25 categories treatment advise differed from literature evidence. For uncomplicated cutaneous leishmaniasis, combination of intralesional antimony with cryotherapy is advised, except for L. guyanensis and L. braziliensis infections, for which systemic treatment is preferred. Treatment of complicated (muco)cutaneous leishmaniasis differs per species. For visceral leishmaniasis, liposomal amphotericin B is treatment of choice. Our study highlights current knowledge about species-directed therapy of leishmaniasis in returning travellers and also demonstrates lack of evidence for treatment of several clinical categories. New data can easily be incorporated in the presented overview. Updates will be of use for clinical decision making and for defining further research.


Phoenix Dan Cong Tea: An Oolong Tea variety with promising antioxidant and in vitro anticancer activity.
Phoenix Dan Cong tea is an Oolong tea produced in Chaozhou, China. Nowaday, the experimental studies on the benefical effects of the Phoenix Dan Cong tea are rare. The objective of this study was to comprehensively evaluate the activity of Phoenix Dan Cong tea aqueous extract (PDCe). We used a series of evaluation methods in the present study to achieve an in-depth understanding and evaluation of the antioxidant and antitumor activity of PDCe. High-performance liquid chromatography (HPLC) studies have indicated that PDCe is rich in catechins such as gallocatechin (GC), epigallocatechin (EGCG) and epicatechin gallate (ECG), with sparse amounts of theaflavins. We discovered that PDCe scavenges ABTS•+ and DPPH• free radicals in a dose-dependent manner. In addition, PDCe can significantly induce apoptosis of MDA-MB231 cells, mainly through the death-receptor-mediated extrinsic apoptotic pathway. Internalized PDCe can not only downregulate intracellular reactive oxygen species levels but also induce oxidative damage to mitochondria in MDA-MB231 cells. Phoenix Dan Cong tea may act as a substitute for natural antioxidants and as a promising anticancer agent due to its protective effect on human health.


Evaluation of chemopreventive response of two cycloxygenase-2 inhibitors, etoricoxib and diclofenac in rat colon cancer using FTIR and NMR spectroscopic techniques.
Non steroidal anti inflammatory drugs (NSAIDs) are efficacious in chemoprevention of colorectal cancer. Therefore, the potential ability of Etoricoxib, a selective cycloxygenase-2(COX-2) inhibitor and Diclofenac, a preferential COX-2 inhibitor are considered in the chemoprevention of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rat model. DMH was injected s.c. for six weeks while Etoricoxib and Diclofenac were fed daily orally alone and also in combination with an weekly subcutaneous injection of 1,2-dimethylhydrazine dihydrochloride (DMH) to the rats. After the treatment period of 6 weeks the animals were sacrificed by an overdose of ether anesthesia and the colonic tissues were removed and studied by the FTIR and NMR Spectroscopic techniques to evaluate the changes occurring in the lipid bilayer of colonic membrane lipids. The alterations in wave number of FTIR spectra as well as the chemical shifts of NMR spectra were recorded which signify the modulation of membrane lipids during colon carcinogenesis and possible cancer prevention by the oral administration of NSAIDs in an experimental model of chemical induced colon carcinogenesis.


Discovery of benthol A and its challenging stereochemical assignment: opening up a new window for skeletal diversity of super-carbon-chain compounds.
Super-carbon-chain compounds (SCCCs) are marine organic molecules featuring long polyol carbon chains with numerous stereocenters. Polyol-polyene compounds (PPCs) and ladder-frame polyethers (LFPs) are two major families. It is highly challenging to establish the absolute configurations of SCCCs. In this century, few new SCCC families have been reported. Benthol A, an aberrant SCCC, was obtained from a South China Sea benthic dinoflagellate that should belong to a new taxon. Its planar structure and absolute configuration, containing thirty-five carbon stereocenters, were unambiguously established by a combination of extensive NMR spectroscopic investigations, periodate degradation of the 1,2-diol groups, ozonolysis of the carbon-carbon double bonds, J-based configurational analysis, NOE interactions, modified Mosher's MTPA ester method, and DFT-NMR 13C chemical-shift calculations aided by DP4+ statistical analysis. Benthol A displayed potent antimalarial activity against Plasmodium falciparum 3D7 parasites. This new molecule combines extraordinary structural features, particularly eight scattered ether rings on a C72 backbone chain, which places it within a new SCCC family between PPCs and LFPs, herein termed polyol-polyether compounds. This suggestion was strongly supported by principal component analysis. The discovery of benthol A does not only provide new insights into the untapped biosynthetic potential of marine dinoflagellates, but also opens up a new window for skeletal diversity of SCCCs.


Factors associated with the seroprevalence of pseudorabies virus in breeding swine from quarantined herds.
Strategies for the elimination of pseudorabies virus (PRV) from swine herds include test and removal, offspring segregation, and depopulation/repopulation. The prevalence of PRV in a herd is a major factor in selection of the most appropriate strategy. The purpose of the study reported here was to describe the prevalence of PRV in adult swine in PRV quarantined herds in Minnesota, and to determine herd factors associated with the seroprevalence. Questionnaires describing the health history of the herd, management practices, and design of the swine facilities were obtained from the owners of 142 quarantined herds. Blood was collected from 29 finishing pigs over the age of 4 months, up to 29 adult females, and all herd boars. Factors considered to be significant in a bivariate analysis were combined in a stepwise multiple logistic regression analysis. The prevalence of PRV-seropositive adults in each herd was bimodally distributed among the 142 herds. In 42 (30%) of the herds, none of the females tested was seropositive, which represented the lower mode. At least 90% of the adults tested were seropositive in 30 (21%) of the herds and represented the higher mode. The odds of the breeding swine of a given herd having a PRV seroprevalence of greater than or equal to 20% as compared with having a seroprevalence of less than 20% was 1.654 times higher per 50 adults in the herd, 13.550 times higher if the finishing pigs were seropositive, 2.378 times higher if sows were housed inside during gestation, and 1.481 times lower per number of years since the imposition of quarantine.(ABSTRACT TRUNCATED AT 250 WORDS)


Sodium-glucose cotransporter 2 inhibitors and cardiovascular outcomes.
Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of cardiovascular (CV) morbidity and mortality. Furthermore, many patients with T2DM have comorbidities that are risk factors for CV disease. While intensive glucose control reduces the risk of diabetic microvascular complications, its relationship to CV outcomes remains unclear. Consequently, the management of CV risk factors in patients with T2DM is complex, and factors other than blood glucose must be considered. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a class of oral glucose-lowering agents, are associated with reductions in blood pressure and body weight, in addition to decreasing hyperglycemia, and therefore have the potential to reduce CV risk in patients with T2DM. The clinical trial results of SGLT2 inhibitors regarding CV safety and outcomes are discussed, including data from the recently published EMPA-REG OUTCOME study. This trial was the first dedicated CV outcomes study to demonstrate that a glucose-lowering agent lowered CV mortality and all-cause mortality, and reduced hospitalization for heart failure in patients with T2DM at high risk of CV events.


Loss of spinal mu-opioid receptor is associated with mechanical allodynia in a rat model of peripheral neuropathy.
The present study investigated whether the loss of spinal mu-opioid receptors following peripheral nerve injury is related to mechanical allodynia. We compared the quantity of spinal mu-opioid receptor and the effect of its antagonists, such as naloxone and CTOP, on pain behaviors in two groups of rats that showed extremely different severity of mechanical allodynia 2 weeks following partial injury of tail-innervating nerves. One group (allodynic group) exhibited robust signs of mechanical allodynia after the nerve injury, whereas the other group (non-allodynic group) showed little allodynia despite having suffered the same nerve injury. In addition, we investigated the quantity of spinal mu-opioid receptor and the effect of its antagonists on pain behaviors after the rats had recovered from mechanical allodynia 16 weeks following nerve injury. Immunohistochemical and Western blot analyses at 2 weeks after nerve injury indicated that spinal mu-opioid receptor content was more reduced in the allodynic group compared to the non-allodynic group. Intraperitoneal naloxone (2 mg/kg, i.p.) and intrathecal CTOP (10 microg/rat, i.t.) administration dramatically induced mechanical allodynia in the non-allodynic group. However, as in naïve animals, neither the loss of spinal mu-opioid receptors nor antagonist-induced mechanical allodynia was observed in the rats that had recovered from mechanical allodynia. These results suggest that the loss of spinal mu-opioid receptors following peripheral nerve injury is related to mechanical allodynia.


[Interaction of transcranial magnetic stimulation and mechanical stimuli].
The influence of different mechanical stimuli on the excitability of spinal motoneurones was investigated in 5 different experiments using transcranial magnetic brain stimulation. A servo controlled moving coil was used to deliver rectangular mechanical stimuli or vibration to the right abductor digiti minimi muscle (ADM) thus exciting spindle primaries. With the ADM relaxed, vibration produced an early enhancement of compound responses (CMAPs) after transcranial magnetic brain stimuli. This is thought to be due to simultaneous arrival of the descending corticospinal volley and of the afferent la volley at the anterior horn cell. With long lasting vibration an enhancement of responses to brain stimuli continued up to 5 seconds after the onset of vibration. Voluntary muscle contraction increased the CMAP. CMAPs measured with voluntary muscle contraction plus mechanical muscle stimulation did not differ from those with muscle contraction alone. Therefore an excitatory influence of mechanical stimuli cannot be seen with ADM contracted.


Ocular toxicities associated with targeted anticancer agents: an analysis of clinical data with management suggestions.
Ocular toxicities are among the most common adverse events resulting from targeted anticancer agents and are becoming increasingly relevant in the management of patients on these agents. The purpose of this study is to provide a framework for management of these challenging toxicities based on objective data from FDA labels and from analysis of the literature. All oncologic drugs approved by the FDA up to March 14, 2015, were screened for inclusion. A total of 16 drugs (12 small-molecule drugs and 4 monoclonal antibodies) were analyzed for ocular toxicity profiles based on evidence of ocular toxicity. Trials cited by FDA labels were retrieved, and a combination search in Medline, Google Scholar, the Cochrane database, and the NIH Clinical Trials Database was conducted. The majority of ocular toxicities reported were low severity, and the most common were conjunctivitis and "visual disturbances." However, severe events including incidents of blindness, retinal vascular occlusion, and corneal ulceration occurred. The frequency and severity at which ocular toxicities occur merits a more multidisciplinary approach to managing patients with agents that are known to cause ocular issues. We suggest a standardized methodology for referral and surveillance of patients who are potentially at risk of severe ocular toxicity.


Production and Properties of Microbial Polyhydroxyalkanoates Synthesized from Hydrolysates of Jerusalem Artichoke Tubers and Vegetative Biomass.
One of the major challenges in PHA biotechnology is optimization of biotechnological processes of the entire synthesis, mainly by using new inexpensive carbon substrates. A promising substrate for PHA synthesis may be the sugars extracted from the Jerusalem artichoke. In the present study, hydrolysates of Jerusalem artichoke (JA) tubers and vegetative biomass were produced and used as carbon substrate for PHA synthesis. The hydrolysis procedure (the combination of aqueous extraction and acid hydrolysis, process temperature and duration) influenced the content of reducing substances (RS), monosaccharide contents, and the fructose/glucose ratio. All types of hydrolysates tested as substrates for cultivation of three strains-C. necator B-10646 and R. eutropha B 5786 and B 8562-were suitable for PHA synthesis, producing different biomass concentrations and polymer contents. The most productive process, conducted in 12-L fermenters, was achieved on hydrolysates of JA tubers (X = 66.9 g/L, 82% PHA) and vegetative biomass (55.1 g/L and 62% PHA) produced by aqueous extraction of sugars at 80 °C followed by acid hydrolysis at 60 °C, using the most productive strain, C. necator B-10646. The effects of JA hydrolysates on physicochemical properties of PHAs were studied for the first time. P(3HB) specimens synthesized from the JA hydrolysates, regardless of the source (tubers or vegetative biomass), hydrolysis conditions, and PHA producing strain employed, exhibited the 100-120 °C difference between the Tmelt and Tdegr, prevailing of the crystalline phase over the amorphous one (Cx between 69 and 75%), and variations in weight average molecular weight (409-480) kDa. Supplementation of the culture medium of C. necator B-10646 grown on JA hydrolysates with potassium valerate and ε-caprolactone resulted in the synthesis of P(3HB-co-3HV) and P(3HB-co-4HB) copolymers that had decreased degrees of crystallinity and molecular weights, which influenced the porosity and surface roughness of polymer films prepared from them. The study shows that JA hydrolysates used as carbon source enabled productive synthesis of PHAs, comparable to synthesis from pure sugars. The next step is to scale up PHA synthesis from JA hydrolysates and conduct the feasibility study. The present study contributes to the solution of the critical problem of PHA biotechnology-finding widely available and inexpensive substrates.


Development of amperometric magnetogenosensors coupled to asymmetric PCR for the specific detection of Streptococcus pneumoniae.
A disposable magnetogenosensor for the rapid, specific and sensitive detection of Streptococcus pneumoniae is reported. The developed procedure involves the use of streptavidin-modified magnetic beads, a specific biotinylated capture probe that hybridizes with a specific region of lytA, the gene encoding the pneumococcal major autolysin, and appropriate primers for asymmetric polymerase chain reaction (PCR) amplification. Capture probes and amplicons specific for S. pneumoniae were selected by a careful analysis of all lytA alleles available. The selected primers amplify a 235-bp fragment of pneumococcal lytA. A detection limit (LOD) of 5.1 nM was obtained for a 20-mer synthetic target DNA without any amplification protocol, while the LOD for the asymmetric PCR amplicon was 1.1 nM. A RSD value of 6.9% was obtained for measurements carried out with seven different genosensors for 1.1-nM aPCR product. The strict specificity of the designed primers was demonstrated by aPCR amplification of genomic DNA prepared from different bacteria, including some closely related streptococci. Direct asymmetric PCR (daPCR), using cells directly from broth cultures of S. pneumoniae, showed that daPCR products could be prepared with as few as 2 colony-forming units (CFU). Furthermore, this methodology did not show any cross-reaction with closely related streptococci such as Streptococcus mitis (or Streptococcus pseudopneumoniae) even when present in the culture at concentrations up to 10(5) times higher than that of S. pneumoniae. Preliminary data for rapid detection of pneumococcus directly in clinical samples has shown that it is possible to discriminate between non-inoculated blood and urine samples and samples inoculated with only 10(3) CFU mL(-1) S. pneumoniae.


Beneficial effects of marine algal compounds in cosmeceuticals.
The name "cosmeceuticals" is derived from "cosmetics and pharmaceuticals", indicating that a specific product contains active ingredients. Marine algae have gained much importance in cosmeceutical product development due to their rich bioactive compounds. In the present review, marine algal compounds (phlorotannins, sulfated polysaccharides and tyrosinase inhibitors) have been discussed toward cosmeceutical application. In addition, atopic dermatitis and the possible role of matrix metalloproteinase (MMP) in skin-related diseases have been explored extensively for cosmeceutical products. The proper development of marine algae compounds will be helpful in cosmeceutical product development and in the development of the cosmeceutical industry.


The effects of melatonin, N-acetylserotonin, and 6-hydroxymelatonin on the ultrastructure of the pinealocytes of the Syrian hamster (Mesocricetus auratus).
The aim of this study was to examine the effects of melatonin as well as of its precursor (N-acetylserotonin) and metabolite (6-hydroxymelatonin) on the ultrastructure of the pinealocytes of the Syrian hamster. The pineal glands of 2-month-old male Syrian hamsters were examined. The animals were divided into the following groups of four animals each: group 1 - melatonin treatment; group 2 - N-acetylserotonin treatment; group 3 - 6-hydroxymelatonin treatment (all substances given subcutaneously at doses of 25 microg per animal between 16.00 and 17.00 h daily for seven weeks). Group 4 was given solvent treatment only and served as controls. The animals were killed by decapitation between 09:00 and 10.00 h. Routine electron microscopical techniques were used to obtain quantitative data on pinealocyte ultrastructure. Melatonin administration did not influence the size of the hamster pinealocytes, whereas administration of N-acetylserotonin and 6-hydroxymelatonin caused a significant reduction in cell size in comparison to the melatonin-treated and control groups. There were changes in the relative volumes of the mitochondria, Golgi apparatus and lysosomes in the pinealocytes of the studied groups, while the volumes of granular endoplasmic reticulum and lipid droplets were unchanged. The dense-core vesicles were more numerous in the pinealocytes of the melatonin and 6-hydroxymelatonin-treated groups in comparison to those of animals treated with N-acetylserotonin or the controls. The changes observed in the ultrastructure of hamster pinealocytes indicate that administration of melatonin as well as of its precursor or metabolite influences the morphology of these cells and also, perhaps, their secretory activity.


Evidence for a functional thymic stromal lymphopoietin signaling axis in fibrotic lung disease.
Thymic stromal lymphopoietin (TSLP) recently has emerged as a key cytokine in the development of type 2 immune responses. Although traditionally associated with allergic inflammation, type 2 responses are also recognized to contribute to the pathogenesis of tissue fibrosis. However, the role of TSLP in the development of non-allergen-driven diseases, characterized by profibrotic type 2 immune phenotypes and excessive fibroblast activation, remains underexplored. Fibroblasts represent the key effector cells responsible for extracellular matrix production but additionally play important immunoregulatory roles, including choreographing immune cell recruitment through chemokine regulation. The aim of this study was to examine whether TSLP may be involved in the pathogenesis of a proto-typical fibrotic disease, idiopathic pulmonary fibrosis (IPF). We combined the immunohistochemical analysis of human IPF biopsy material with signaling studies by using cultured primary human lung fibroblasts and report for the first time, to our knowledge, that TSLP and its receptor (TSLPR) are highly upregulated in IPF. We further show that lung fibroblasts represent both a novel cellular source and target of TSLP and that TSLP induces fibroblast CCL2 release (via STAT3) and subsequent monocyte chemotaxis. These studies extend our understanding of TSLP as a master regulator of type 2 immune responses beyond that of allergic inflammatory conditions and suggest a novel role for TSLP in the context of chronic fibrotic lung disease.


Using process-based models to filter out natural variability in observed concentrations of nitrogen and phosphorus in river water.
Advances in process-based modelling of loads of nitrogen and phosphorus carried by rivers have created new possibilities to interpret time series of water quality data. We examined how model runs with constant anthropogenic forcing can be used to estimate and filter out weather-driven variation in observational data and, thereby, draw attention to other features of such data. An assessment of measured and modelled nutrient concentrations at the outlets of 45 Swedish rivers provided promising results for total nitrogen. In particular, joint analyses of observational data and outputs from the catchment model S-HYPE strengthened the evidence that downward trends in nitrogen were due to mitigation measures in agriculture. Evaluation of modelled and observed total phosphorus concentrations revealed considerable bias in the collection or chemical analysis of water samples and also identified weaknesses in the model outputs. Together, our results highlight the need for more efficient two-way communication between environmental modelling and monitoring.


[Reflections on the essence of family-centered care].
The aim of this article is to explore the essence of family-centered care; what it is and what it is not. The article approaches the concept of family-centered care from the points of view of both epistemology and ontology. The new concept of family-centered care had its beginning in the consumer movement and feminism in the 1960s, when patients, families, and health professionals in departments of obstetrics and pediatrics began to be aware of the needs of patients whole families. The concept of family-centered care emphasizes respect, support, and collaborative partnership between family members and health professionals. The new knowledge developed out of a practical need, affecting the old paradigm of patient care. New concepts and new knowledge emerged, causing a paradigm shift that influenced both policies and research at the same time. The body of knowledge in the profession was then disseminated through the expansion of education.


[Basic areas of medical science in Uzbekistan].
The paper considers the issues of medicine development in the Republic of Uzbekistan and the contribution made by prominent scientists developing effective methods for diagnosing and treating different diseases in medical science. A great part is assigned to medical science advances in our country. To solve the urgent problems of public health, much attention is given to the training of scientific manpower, the setting up of specialized research and practical medical centers of different profile, research laboratories of medical higher educational establishments as a base for conducting researches and investigations, which will be able to improve the quality of medical care to the population and corresponds to a health care reform program.


Endurance exercise as a countermeasure for aging.
We determined whether reduced insulin sensitivity, mitochondrial dysfunction, and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and ATP production in mitochondria isolated from vastus lateralis biopsies of 42 healthy sedentary and endurance-trained young (18-30 years old) and older (59-76 years old) subjects. Expression of proteins involved in fuel metabolism was measured by mass spectrometry. Citrate synthase activity, mitochondrial DNA (mtDNA) abundance, and expression of nuclear-encoded transcription factors for mitochondrial biogenesis were measured. SIRT3, a mitochondrial sirtuin linked to lifespan-enhancing effects of caloric restriction, was measured by immunoblot. Insulin-induced glucose disposal and suppression of endogenous glucose production were higher in the trained young and older subjects, but no age effect was noted. Age-related decline in mitochondrial oxidative capacity was absent in endurance-trained individuals. Although endurance-trained individuals exhibited higher expression of mitochondrial proteins, mtDNA, and mitochondrial transcription factors, there were persisting effects of age. SIRT3 expression was lower with age in sedentary but equally elevated regardless of age in endurance-trained individuals. The results demonstrate that reduced insulin sensitivity is likely related to changes in adiposity and to physical inactivity rather than being an inevitable consequence of aging. The results also show that regular endurance exercise partly normalizes age-related mitochondrial dysfunction, although there are persisting effects of age on mtDNA abundance and expression of nuclear transcription factors and mitochondrial protein. Furthermore, exercise may promote longevity through pathways common to effects of caloric restriction.


Selenium deficiency and Balkan endemic nephropathy.
Data on selenium (Se) deficiency in Yugoslavia are summarized. These data include the selenium contents of stream sediments, rocks, soils, cereal crops grown in these soils, and human serum and scalp hair from several towns and regions. Analyses of human tissues in Yugoslavia show very low Se concentrations in both endemic and nonendemic areas. In some regions, including those with endemic villages, selenium contents of grains and human serum and hair are extremely low, approaching those in the low-selenium zone in China. According to the biological function of selenium, a very low intake of selenium may be a fundamental underlying condition that would predispose persons to attack by other agents in the development of Balkan endemic nephropathy.


Increased Serum Prolactin and Excessive Daytime Sleepiness: An Attempt of Proof-of-Concept Study.
The objectives of this study were: (1) to identify subjects with hyperprolactinemia in a clinical sample of patients; (2) to compare the neurologic, psychiatric, and sleep conditions found in patients subgrouped by excessive daytime sleepiness (EDS) and hyperprolactinemia; and (3) to identify patients with hyperprolactinemia and EDS not supported by the presence of any other neurologic, psychiatric, or sleep disorder, or substance/medication use. A retrospective chart review of inpatients was carried out in order to identify all patients in whom the prolactin (PRL) serum levels were determined. A total of 130 subjects were retrieved: 55 had increased levels of PRL, while the remaining 75 participants had normal PRL levels. EDS was reported by 32 (58.2%) participants with increased PRL and 34 (45.3%) with normal PRL. Obstructive sleep apnea or other sleep or neurologic/psychiatric conditions could explain EDS in all participants with normal PRL. Among subjects with increased PRL, eight had no other neurologic/psychiatric or sleep disorder (or drug) potentially causing EDS; these participants, at polysomnography, had time in bed, sleep period time, and total sleep time longer than those with EDS associated to another condition. These findings can be considered as a preliminary indication of a role of hyperprolactinemia in EDS and represent a basis for future controlled studies able to test this hypothesis in a reliable, objective, and methodologically more appropriate way.


Suppressive effect of acetylsalicylic acid on erythropoietin-responsive cells in mice.
The time-response curve for RBC-59Fe uptake following i.p. injections of 3 doses of 5 mg of acetylsalicylic acid (ASA) at 4 hour interval into normal, nonpolycythemic mice, shows a maximal depression (35% of normal) at 3 days after ASA with return to almost normal values by 7 days. The effect is dose-related, showing a plateau with doses of ASA above 5 mg/4 hr. The shape of the time-response curve indicates that the more mature cells in the erythron are not affected by ASA and that the major effect of the drug must be on earlier erythroid cells. Administration of ASA prior to administration of erythropoietin (Epo) into post-hypoxic polycythemic mice depresses the incorporation of 59Fe into erythrocytes. The depression of radioiron uptake is similar when ASA is given prior to or simultaneously with Epo. When ASA is given 24 hr after injection of Epo, suppression is less marked. These results suggest a suppressive effect of the drug on the erythropoietin-responsive cells (ERC).


[Idiopathic hypercalciuria. Differential diagnosis].
In 50 children with hematuria or urolithiasis and idiopathic hypercalciuria, and in 15 control children, urinary calcium/creatinine concentration rates were measured after fasting and after calcium loading. Patients were classified into two groups depending on the results of an orally administered calcium loading test. Children were considered to have absorptive hypercalciuria (42%) when they had low fasting urinary calcium/creatinine concentration ratio (less than 0.21), and a large increase of this index after calcium administration (greater than 0.28). Patients were labeled as renal hypercalciuria (32%) if they had high fasting urinary calcium/creatinine concentration ratio (greater than 0.21), and variable increases of it after calcium overload. A third group of children (26%), were not classifiable by means of this test. Our data support the contention that this simple ambulatory test is very useful in the diagnostic workup of idiopathic hypercalciuria.


Factors Associated with and Barriers to the Journal Publication of Oral Abstracts from the American Podiatric Medical Association.
Not all abstracts accepted for oral presentation at the annual conference of the American Podiatric Medical Association ultimately go on to successfully navigate the peer-review process to achieve journal publication despite its obvious merits. The purpose of the present study was to identify the factors associated with and barriers to journal publication and time to publication for oral abstracts from the American Podiatric Medical Association conference from 2010 to 2014. Databases containing information on the abstracts were procured and predictor variables categorized as abstract- or author-specific. Bivariate analysis was conducted using the Mann-Whitney U test, Fisher's exact test, chi-square test of independence, or Spearman rank correlation. Multivariable logistic regression and generalized linear regression models were used to analyze predictor variables. A questionnaire was distributed to the primary authors of any unpublished abstracts to determine the current status of the abstract, in addition to the reasons for the failure to pursue or achieve journal publication. Overall, oral abstracts by authors without a formal research degree were published more often than abstracts by authors with a research degree, as were funded projects (P = .031). No other associations were identified between any of the abstract- and author-specific variables and successful conversion of an oral abstract to a journal publication or the time to publication. Six barriers questionnaires were completed. At the time of the survey, two oral abstracts had since achieved publication, two had been submitted for publication but were rejected, and two had never been submitted. The principal reason cited by the authors for the failure to pursue or achieve journal publication was insufficient time for manuscript preparation.


The role of endoscopy after upper gastrointestinal bleeding in sub-Saharan Africa: A prospective observational cohort study.
Upper gastrointestinal (UGI) bleed is a common surgical disease in sub-Saharan Africa where there is often a lack of diagnostic and interventional adjuncts such as endoscopy. This study sought to characterize the role of endoscopy in management of acute UGI bleeding. This is a prospective observational analysis of adults presenting with an UGI bleed to a tertiary center in Lilongwe, Malawi, over two years. Patients were classified as having no endoscopy, diagnostic endoscopy, or endoscopy with variceal banding. Bivariate, survival analysis, and logistic regression analyses were used to compare intervention cohorts. 293 patients were included with 49 patients (16.7%) receiving endoscopy with banding, 65 (22.2%) patients receiving diagnostic endoscopy only, and 179 (61.1%) receiving no endoscopy. Upon survival analysis comparing to the no endoscopy group, cox hazard modelling showed an adjusted hazard ratio over 30 days of 0.12 (95% CI 0.02, 0.88, p=0.038) for the endoscopic banding group and a hazard ratio of 0.39 (95% CI 0.13, 1.16, p=0.090) for the diagnostic endoscopy only group. Physical exam findings consistent with cirrhosis and decreasing age were independent predictors of an endoscopic diagnosis of variceal bleeding. Esophagogastric varices are a common cause of UGI bleeding in sub-Saharan Africa and can be predicted with age and physical exam findings. Endoscopy with variceal banding has a survival benefit for patients presenting with acute UGI bleed even with relatively low utilization. Appropriately triaging patients with likely variceal bleeding and improving endoscopy capacity would likely have a significant impact on mortality.


Changes in muscle morphology in dialysis patients after 6 months of aerobic exercise training.
In the present study we investigated the effect of a 6-month aerobic exercise programme on the morphology of the gastrocnemius muscle of end-stage renal disease (ESRD) patients. Twenty-four ESRD patients volunteered to participate in the training programme and underwent muscle biopsy before training. Eighteen patients completed the training programme of whom nine agreed to a post-training biopsy (one woman and eight men, mean age 56 +/- 15 years). Data are presented for the nine subjects who were biopsied before (PRE) and after training (POST) and separately for the 15 subjects for whom we only have a biopsy before training (cross-sectional group). There were no significant differences (P > 0.05) in fibre type distribution or myosin heavy chain (MyHC) expression between the cross-sectional and PRE/POST groups. The mean cross-section fibre area after training (POST) increased by 46% compared with the PRE training status (P < 0.01). The proportion of atrophic fibres decreased significantly after training in type I, IIa and IIx fibre populations (from 51 to 15%, 58 to 21% and 62 to 32%, respectively). Significant differences were also found in capillary contact per fibre (CC/F), with the muscle having 24% (P < 0.05) more CC/F compared with the PRE training status. No significant differences in cytochrome c oxidase concentration were found between the groups. In conclusion, exercise appeared to be beneficial in renal rehabilitation by correcting the fibre atrophy, increasing the cross-section fibre area and improving the capillarization in the skeletal muscle of renal failure patients.


Endogenous digoxin-like immunoreactive factors eliminated from serum samples by hydrophobic silica-gel extraction and enzyme immunoassay.
Elimination of endogenous digoxin-like immunoreactive factors (DLIF) that interfere with accurate measurement of digoxin requires use of a highly specific anti-digoxin antibody, or that DLIF be separated from digoxin before immunoassay. Several commercial digoxin-assay kits include a step for separating serum proteins and other substances from digoxin before immunoassay. We tested six different immunoassay methods (some having pretreatment steps) for their ability to detect DLIF in serum from patients in renal failure, pregnant women, and neonates, all of whom were not taking digoxin. Extracting digoxin on a column of derivatized silicagel eliminated detectable DLIF from serum as measured by enzyme immunoassay (EMIT; Syva Co.), but recovery of added digoxin was quantitative. In contrast, protein precipitation with 5-sulfosalicylic acid left significant amounts of DLIF in samples, most probably because the procedure (TDx assay; Abbott Labs.) disrupted protein-DLIF binding. A glass-bead radioimmunoassay (Immophase; Corning Medical) had the most digoxin-specific antisera. By preparative silica-gel-chromatography of serum we could eliminate or significantly minimize inaccurate digoxin measurements attributable to endogenous DLIF.


Insights into Emydid Turtle Cytogenetics: The European Pond Turtle as a Model Species.
Our knowledge of Testudines evolution is limited by the lack of modern cytogenetic data. Compared to other reptiles, there is little information even on chromosome banding, let alone molecular cytogenetic data. Here, we provide detailed information on the karyotype of the European pond turtle Emys orbicularis, a model Emydidae, employing both chromosome banding and molecular cytogenetics. We provide a high-resolution G-banded karyotype and a map of rDNA genes and telomeric sequences using fluorescence in situ hybridization. We test hypotheses of sex-determining mechanisms in Emys by comparative genomic hybridization to determine if Emys has a cryptic sex-specific region. Our results provide valuable data to guide future efforts on genome sequencing and anchoring in Emydidae and for understanding karyotype evolution in Testudines.


Allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic or accelerated phase.
Eight patients with Ph1-positive chronic myelogenous leukemia (CML) in chronic or accelerated phase received high-dose cyclophosphamide, total body irradiation, and bone marrow transplantation from an HLA-identical sibling donor. All patients had prompt engraftment and achieved complete hematologic remission. Six patients remain alive and in continuous remission with a normal bone marrow karyotype 3-20+ mo posttransplant. One patient died from cytomegalovirus interstitial pneumonitis. Only one patient who was transplanted in accelerated phase relapsed 6.5 mo posttransplant and died in blast crisis. High-dose combined modality therapy is capable of producing sustained complete remissions in patients with CML treated during chronic or accelerated phase.


The relationships of change in physical activity with change in depression, anxiety, and burnout: a longitudinal study of Swedish healthcare workers.
The purpose of the present study was to examine whether intraindividual changes in physical activity were correlated with intraindividual changes in mental health (depression, anxiety, and burnout) across four measurement time-points over 6 years, both from between-person and within-person perspectives. Health care workers (N = 3717; mean age = 46.9; SD = 10.0) were the target population in this study, which is part of a larger longitudinal survey that included questionnaires on physical activity levels and mental health (depression, anxiety, and burnout) at four time points across 6 years (2004-2010). Physical activity was assessed with an adapted version of the widely used 1-item, 4-level Saltin Grimby Physical Activity Level Scale (SGPALS). Depression, anxiety, and burnout were assessed using the Hospital Anxiety and Depression (HAD) scale and the Shirom-Melamed Burnout Questionnaire (SMBQ). Bivariate latent growth curve models were used to analyze the associations of change between physical activity and mental health. Baseline levels of physical activity were moderately associated with baseline levels of mental health (rs = -.27 to -.40, ps < .01). Changes in physical activity were moderately to strongly associated (rs = -.57 to -.79, ps <. 01) with change in mental health at the between-person (correlated change) level and significantly, but weakly (rs = -.08 to -.14, ps <.01), associated with change at the within-person (coupled change) level of analysis. Changes in physical activity were associated with, and traveled together with, changes in depression, anxiety, and burnout across time. Changes in physical activity, and not only current or previous levels of activity, may be important to consider in preventive work linked to mental health within this population.


Synthesis and binding affinity of bidentate phenothiazines with two different photoactive groups.
The development of targeted, bidentate photoaffinity reagents for mapping the interacting domains of calmodulin (CaM) with the enzymes that it regulates required the synthesis and evaluation of the binding affinity of various phenothiazines. These photoaffinity reagents would possess a photoactive 3-azidophenothiazine group for cross-linking the hydrophobic binding domain of CaM, a second photoactive benzophenone group that would be activated at a different wavelength than the 3-azidophenothiazine group, and a suitable radiolabel. Difficulties were encountered in identifying those structural features that would be compatible with the introduction of a benzophenone group, with the solubility of these benzophenone-substituted phenothiazines, and with the ability of these phenothiazines to inhibit the calmodulin-mediated activation of phosphodiesterase. Solutions to this problem involved the preparation of phenothiazines possessing a quaternary ammonium salt, a zwitterionic amino acid, or a carbohydrate moiety. The phenothiazines that possessed photoactive 3-azido and benzophenone groups and in which one of the piperazine nitrogens in the side chain was converted to a quaternary, N-methylammonium iodide inhibited the calmodulin-mediated activation of phosphodiesterase at a level comparable to that of chlorpromazine.