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Background The major source of dietary iodine for the Sri Lankan population is iodized salt. The recommended fortification level of iodine is 15.0–30.0 ppm. Both excessive and insufficient iodine levels are harmful to the human body. Inadequate consumption of iodine leads to iodine deficiency disorders and excessive intake causes iodine-induced hyperthyroidism. Methods This study assessed the iodine content in commercially available salt products and evaluated the stability of iodine under different storage conditions. Packeted crystal and powdered salt products were used to determine the total iodine content by analyzing both iodide (I−) and iodate (IO3−). The effect of temperature and packaging material on the stability of iodine was also recorded. Results The results revealed that five products out of ten exceeded the recommended iodine level and were in the range of 31.60 ± 1.5 to 42.19 ± 3.48 ppm. The iodine content of four products was within the recommended fortified levels, and one had a lower amount of 12.77 ± 0.35 ppm. The mean iodine content of powdered salt was 35.08 ppm and 27.25 ppm in crystal salt. There was no significant effect of temperature at 25°C, 45°C, and 95°C on total iodine level and iodine level by iodate. The total mean iodine loss after heating to 95°C for 30 minutes was 5.0% in powdered salt and 8.7% in crystal salts. Total iodine retained during storage in opened containers for one week in glass containers was 90.78% in crystal salt and 87.11% in powdered salt. The percentage of iodine retained in plastic containers was 83.77% in crystal salt and 71.6% in powdered salt. In coconut shell containers 61.94% and 49.23% iodine retained was observed in crystal salt and powdered salt respectively. The lowest iodine retain was in gunny bags 54.24% in crystal salt and 44.77% in powdered salt. Conclusions Most of the commercially available salt products (50%) contain a higher amount of iodine than the recommended fortification levels. Short-term exposure of iodized salt to cooking temperatures and in different storage containers didn’t show any remarkable reduction in the levels of iodine.

Studies on nutritional status of state employees are limited and therefore the present study was conducted to determine the nutritional status of aselected sample of employees attached to the University of Sri Jayewardenepura (USJP), who directly involve in facilitating the academic activities of the University. This is a cross-sectional study carried out by interviewing 130 non-academic members of USJP staff for collecting information on their socio-demographic factors, physical activity levels and food habits. Body Mass Index (BMI) and Waist to Hip ratio (WHR) were calculated according to the WHO anthropometric standards while seven-day food consumption was recorded to assess the food and energy intake in the participants. The prevalence of overweight and obesity in the sample was32.3% and 10.8% respectively while 53.8% and 63.9% of the participants had WC (waist circumference) and WHR. Among the participants, 79.2% of members had a sedentary lifestyle spending most of their time sitting without exercises at work and at home. Moreover, they showed a significant relationship with overweight and obesity (r=0.4, p

Slow-release fertilizers based on nanomaterials have recently proven promise in increasing nitrogen use efficiency by plants and reduction in environmental hazards. We have previously reported the ...

Hemophilia B is a blood clotting disorder caused by deficient activity of coagulation factor IX (FIX). Multiple recombinant FIX proteins are currently approved to treat hemophilia B, and several gene therapy products are currently being developed. Codon optimization is a frequently used technique in the pharmaceutical industry to improve recombinant protein expression by recoding a coding sequence using multiple synonymous codon substitutions. The underlying assumption of this gene recoding is that synonymous substitutions do not alter protein characteristics because the primary sequence of the protein remains unchanged. However, a critical body of evidence shows that synonymous variants can affect cotranslational folding and protein function. Gene recoding could potentially alter the structure, function, and in vivo immunogenicity of recoded therapeutic proteins. Here, we evaluated multiple recoded variants of F9 designed to further explore the effects of codon usage bias on protein properties. The detailed evaluation of these constructs showed altered conformations, and assessment of translation kinetics by ribosome profiling revealed differences in local translation kinetics. Assessment of wild-type and recoded constructs using a major histocompatibility complex (MHC)-associated peptide proteomics assay showed distinct presentation of FIX-derived peptides bound to MHC class II molecules, suggesting that despite identical amino acid sequence, recoded proteins could exhibit different immunogenicity risks. Posttranslational modification analysis indicated that overexpression from gene recoding results in suboptimal posttranslational processing. Overall, our results highlight potential functional and immunogenicity concerns associated with gene-recoded F9 products. These findings have general applicability and implications for other gene-recoded recombinant proteins.

Structural health monitoring (SHM) has become an integral part of essential and costly to replace infrastructures such as bridges and buildings which degrade during their lifetime. Understanding the structural behaviour of these infrastructures is critical for assuring their structural integrity and safe operating conditions. In this study, the structural performance of a reinforced concrete beam was examined under flexural loading. Distributed optical fibre sensor (DOFS) was attached to the beam’s bottom surface, and Optical Backscattered Reflectometry (OBR) technology was used to measure the surface strain. A three-point bending test was performed, and the sensor responses were acquired. Unusual high strain peaks were observed at the bottom surface of the beam due to the formation of hairline cracks. Subsequently, the Concrete Damaged Plasticity (CDP) based Finite Element Analysis (FEA) was performed to simulate the plastic behaviour of concrete beam using ABAQUS 2019 commercial software. The FEA results have strong agreement with the strain pattern observed from the DOFS. Therefore, DOFS and CDP technique based FEA can be successfully used to investigate the plastic damage pattern inside the concrete beam and distributed sensing demonstrates a greater capacity for long-term monitoring of the structural health of concrete structures.

Synonymous codons occur with different frequencies in different organisms, a phenomenon termed codon usage bias. Codon optimization, a common term for a variety of approaches used widely by the biopharmaceutical industry, involves synonymous substitutions to increase protein expression. It had long been presumed that synonymous variants, which, by definition, do not alter the primary amino acid sequence, have no effect on protein structure and function. However, a critical mass of reports suggests that synonymous codon variations may impact protein conformation. To investigate the impact of synonymous codons usage on protein expression and function, we designed an optimized coagulation factor IX (FIX) variant and used multiple methods to compare its properties to the wild-type FIX upon expression in HEK293T cells. We found that the two variants differ in their conformation, even when controlling for the difference in expression levels. Using ribosome profiling, we identified robust changes in the translational kinetics of the two variants and were able to identify a region in the gene that may have a role in altering the conformation of the protein. Our data have direct implications for codon optimization strategies, for production of recombinant proteins and gene therapies.

The liver is the primary source of a large number of plasma proteins and plays a critical role in multiple biological processes. Inadequate oxygen supply characterizing various clinical settings such as liver transplantation exposes the liver to hypoxic conditions. Studies assessing hypoxia-induced global translational changes in liver are lacking. Here, we employed a recently developed ribosome-profiling technique to assess global translational responses of human primary hepatocytes exposed to acute hypoxic stress (1% O2) for the short term. In parallel, transcriptome profiling was performed to assess mRNA expression changes. We found that translational responses appeared earlier and were predominant over transcriptional responses. A significant decrease in translational efficiency of several ribosome genes indicated translational inhibition of new ribosome protein synthesis in hypoxia. Pathway enrichment analysis highlighted altered translational regulation of MAPK signaling, drug metabolism, oxidative phosphorylation, and nonalcoholic fatty liver disease pathways. Gene Ontology enrichment analysis revealed terms related to translation, metabolism, angiogenesis, apoptosis, and response to stress. Transcriptional induction of genes encoding heat shock proteins was observed within 30 min of hypoxia. Induction of genes encoding stress response mediators, metabolism regulators, and proangiogenic proteins was observed at 240 min. Despite the liver being the primary source of coagulation proteins and the implicated role of hypoxia in thrombosis, limited differences were observed in genes encoding coagulation-associated proteins. Overall, our study demonstrates the predominance of translational regulation over transcription and highlights differentially regulated pathways or biological processes in short-term hypoxic stress responses of human primary hepatocytes.NEW & NOTEWORTHY The novelty of this study lies in applying parallel ribosome- and transcriptome-profiling analyses to human primary hepatocytes in hypoxia. To our knowledge, this is the first study to assess global translational responses using ribosome profiling in hypoxic hepatocytes. Our results demonstrate the predominance of translational responses over transcriptional responses in early hepatic hypoxic stress responses. Furthermore, our study reveals multiple pathways and specific genes showing altered regulation in hypoxic hepatocytes.

The diagnostic accuracy of the I3M to assess the legal age of 18 years has already been tested in several specific-population samples. The left lower third molar has been extensively used for discriminating between minors and adults. This research aimed to compare the usefulness of lower third molar maturity indexes, from both left and right side (I3ML and I3MR), in samples originating from four distinct continents in order to examine possible differences in their accuracy values. For this purpose, a sample of 10, 181 orthopantomograms (OPGs), from Europe, Africa, Asia and America, was analysed and previously scored in other studies. The samples included healthy subjects with no systemic disorders with both third molars and clear depicted root apices. Wilcoxon Signed Rank test for left and right asymmetry did not show any significant differences. Data about sensitivity, specificity, predictive values, likelihood ratio and accuracy were pooled together and showed similar results for I3ML and I3MR, respectively. In addition, all these quantities were high when only the I3MR was considered to discriminate between adults and minors. The present referable database was the first to pool third molar measurements using panoramic radiographs of subjects coming from different continents. The results highlighted that both I3ML and I3MR are reliable indicators for assessing the legal age of 18 years old in those jurisdictions where this legal threshold has been set as the age of majority.

Rainfall is an important climatic factor influencing soil formation in Sri Lanka. Therefore, the major soil types are initially grouped to soils of the Wet, Intermediate, and Dry zones according to major climatic regions. Subsequently, the soils of the Wet and Intermediate zones are grouped according to the elevation, soils occurring in the up, mid and low countries. The Dry zone consists of only the low country and therefore, grouped under soils derived from erosional surfaces, coastal plains, and the flood plains. Near the coastal areas of Dry zone, the landscape is flat and changes to undulating toward Intermediate zone. Sketches showing such landscapes have been included in the chapter. Out of 118 soil series identified and mapped 54 soil series occur in the Dry zone. As the soil maps are too large to include in this book, one page from soil maps is included with references for further reading. Each soil series is classified according to Soil Taxonomy and World Resource Base (WRB-FAO) legend depending on the availability of data. More detail classification was done using the WRB classification as it does not demand detail information as soil moisture regimes which are needed for Soil Taxonomy. The local name used from the 1972 classification which are named as Great Soil Groups are also given in the tables. For each of the physiographic grouping occurring in the given climatic zone one characteristic (benchmark) soil series is described in detail with the color photographs of the landscape and soil profile .

The folivorous beetle Cassida rubiginosa was introduced to New Zealand to control the weed, Californian thistle (Cirsium arvense). Although Californian thistle is the primary host, many other thistles are accepted hosts. The objective of this study was to test if the beetle can reduce the fitness of marsh thistle (Cirsium palustre). A potted plant experiment was established with four treatments (0, 50, 100, and 200 larvae/plant). Plant growth (width, height, and number of branches) and reproductive performance (number of flowers, seeds, seed weight and percent germination) parameters were measured. No significant differences were found for any of the measured parameters, except percent germination. Higher larval densities (100 and 200) resulted in approximately 10% less germination compared with lower densities (0 and 50). Under these experimental conditions, C. rubiginosa had minimal impact on the performance of marsh thistle. For the beetle to have an impact, it would likely need to attack smaller, non-bolting rosettes, or be combined with additional stressors that might be encountered in a natural field population.

Ribosome profiling provides the opportunity to evaluate translation kinetics at codon level resolution. Here, we describe ribosome profiling data, generated from two HEK293T cell lines. The ribosome profiling data are composed of Ribo-seq (mRNA sequencing data from ribosome protected fragments) and RNA-seq data (total RNA sequencing). The two HEK293T cell lines each express a version of the F9 gene, both of which are translated into identical proteins in terms of their amino acid sequences. However, these F9 genes vary drastically in their codon usage and predicted mRNA structure. We also provide the pipeline that we used to analyze the data. Further analyzing this dataset holds great potential as it can be used i) to unveil insights into the composition and regulation of the transcriptome, ii) for comparison with other ribosome profiling datasets, iii) to measure the rate of protein synthesis across the proteome and identify differences in elongation rates, iv) to discover previously unidentified translation of peptides, v) to explore the effects of codon usage or codon context in translational kinetics and vi) to investigate cotranslational folding. Importantly, a unique feature of this dataset, compared to other available ribosome profiling data, is the presence of the F9 gene in two very distinct coding sequences.

Synonymous variants within coding regions may influence protein expression and function. We have previously reported increased protein expression levels ex vivo (~120% in comparison to wild-type) from a synonymous polymorphism variant, c.354G>A [p.P118P], of the ADAMTS13 gene, encoding a plasma protease responsible for von Willebrand Factor (VWF) degradation. In the current study, we investigated the potential mechanism(s) behind the increased protein expression levels from this variant and its effect on ADAMTS13 physico-chemical properties. Cell-free assays showed enhanced translation of the c.354G>A variant and the analysis of codon usage characteristics suggested that introduction of the frequently used codon/codon pair(s) may have been potentially responsible for this effect. Limited proteolysis, however, showed no substantial influence of altered translation on protein conformation. Analysis of post-translational modifications also showed no notable differences but identified three previously unreported glycosylation markers. Despite these similarities, p.P118P variant unexpectedly showed higher specific activity. Structural analysis using modeled interactions indicated that subtle conformational changes arising from altered translation kinetics could affect interactions between an exosite of ADAMTS13 and VWF resulting in altered specific activity. This report highlights how a single synonymous nucleotide variation can impact cellular expression and specific activity in the absence of measurable impact on protein structure.

Hettiarachi, D.K., Cripps, M.G., Cruikshank, R.H. & Rostás, M. (2017) A phylogenetic approach to assessing olfactory host selection in Cassida rubiginosa (Chrysomelidae). In Invertebrate Ecology of Australasian Grasslands. Proceedings of the Ninth ACGIE (ed S.N. Johnson), pp. 59-61. Western Sydney University, Hawkesbury, NSW, Australia.

A field survey was carried out to determine the soil and leaf sulfur (S) status in some tea estates where urea based fertilizer mixtures had been used continuously for more than ten years. Fourteen tea estates in Ratnapura, Passara, Kottawa, and Deniyaya regions were selected for this study. Five extractants were used to extract soil-S. The results indicate that the mean soil S varied from 22 to 229 μg g−1 at 0–15 cm depth. The range of extractable-S extracted by ammonium acetate, KCl, NaHCO3, Ca(H2PO4)2 and water for Deniyaya, Kottawa, Passara, and Ratnapura regions varied from 18–91, 18–55, 13–302, and 15–455 μg g−1, respectively, at 0–15 cm soil depth. Linear correlation coefficient between the five extractants was low. The total leaf S varied from 0.12 to 0.41% in the locations studied.

Long-term effects of applying locally mined crushed crystalline dolomitic-limestone, to tea (Camellia sinensis L) are being investigated in field trials, in Sri Lanka. From these trials, it appeared that an understanding of the roles of both Mg and Ca during liming was necessary to understand the nutrition of the tea plant. A pot experiment was carried out in the glasshouse, to investigate the effect of raising Mg status of soils of differing soil pH and Ca availability using a Camellia species, in particular concern to the Sri Lankan tea industry. To address this concern, treatments that supplied Mg and/or Ca in the presence or absence of liming materials were used. Leaves of plants were harvested after 6, 12 and 24 months, and analyzed for P, K, Mg, Ca, Al, Mn, Fe, Cu, Zn and B using Inductively Coupled Plasma-Atomic Emission Spectrophotometer (ICP-AES). Total N contents were obtained by combusting dried material in a NC analyzer. Soils in the pots were removed and dismantled from the roots lump, determ...

Maruca vitrata (Geyer) is a serious insect pest of tropical legumes. In Sri Lanka, yield losses due to Maruca damage in pigeonpea [Cajanus cajan (L.) Millsp.] range up to 100%. The development of resistant cultivars and germplasm is one of the best means of control. The objectives of this study were to screen 271 accessions for resistance to M. vitrata and evaluate reaction of lines selected from the promising accessions. The high level of natural incidence of Maruca in Sri Lanka provided an opportunity for evaluation of germplasm at Field Crops Research and Development Institute, Maha Illuppallama. Screening of the germplasm accessions revealed large variation in Maruca damage to flowers and pods. On average, the Maruca damage in determinate accessions (66–75%) was higher than that of nondeterminate accessions (41–50%). Resistant plants from four determinate and 12 nondeterminate accessions were selected. Further selection for resistance to Maruca damage among and within lines derived from the resistant plants was exercised for six generations under nonsprayed field conditions. Under insecticide-free conditions, the selections from two accessions showed significant yield advantages over controls. Data on pod damage and larval counts indicated that the resistance was conditioned through yield compensation mechanisms. In pigeonpea, this is the first report of the selection of Maruca resistant lines. Further studies showed that by using the resistant genotypes it is possible to reduce the number of insecticide sprays for economic yields.

Among the many opioid peptides developed to date as nonaddictive analgesics, biphalin has exhibited extraordinary high potency and many other desirable characteristics. Biphalin is an octapeptide consisting of two monomers of a modified enkephalin, attached via a hydrazine bridge, and with the amino acids assembled in a palindromic sequence. Its structure is (Tyr-d-Ala-Gly-Phe-NH-)-2. However, this unique peptide, like any other synthetic peptide, needs strict quality control because of certain drawbacks associated with peptide synthesis. This paper discusses our approaches to characterizing and analyzing biphalin. Many techniques were used, including elemental analysis, amino acid analysis, amino acid sequence analysis (AASA), mass spectrometry (MS), 1H-NMR, 1H-correlated spectroscopy (COSY)-NMR, high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Electrospray ionization (ESI) mass spectrometry, which included both ESI-MS and ESI-MS/MS, was performed to confirm the full sequence because AASA results alone verified only the monomer sequence, and not the full sequence. Although the 1H-NMR results led to a preliminary assignment of many protons, the 1H COSY-NMR results allowed for unequivocal assignment of almost all protons. Peptide purity was determined using two techniques, reversed-phase HPLC and CE. The counter-ion of the peptide, trifluoroacetic acid, was determined by CE, using an indirect detection method developed previously in our laboratory. This paper illustrates successful application of nonconventional techniques to characterize and analyze a structurally modified peptide, biphalin, when standard techniques for peptide analysis are inadequate.

SummaryClinical and experimental studies have suggested that unfractionated heparin (UFH) effects malignancy progression. We reviewed all published clinical reports concerning the effects of UFH, as compared to no treatment on survival of cancer patients. Studies were classified on methodological strength and subdivided as to whether therapeutic or prophylactic dosages of UFH were used. Mortality rates after 3 years were extracted or calculated. One randomized study that evaluated the use of UFH in therapeutic dosages in patients with small cell lung carcinoma reported on an improved survival (odds ratio (OR) 0.64; 95% confidence interval (CI): 0.25 to 1.62). A detrimental effect was observed in 2 randomized studies which investigated the effects of intraportal UFH treatment in a prophylactic dose after surgery for gastrointestinal cancer (OR 1.66; 95% CI: 1.02 to 2.71). In contrast, level 2 studies in which either therapeutic or prophylactic dosages of UFH on mortality of patients with gastrointestinal cancer were evaluated, showed OR of 0.58 (95% CI; 0.11-3.13) and 0.65 (95% CI 0.51 to 0.84), respectively. We conclude that there is no convincing evidence of either positively or negatively effects of UFH on survival of patients with malignancy.Harry R. Büller is an Established Investigator of the Dutch Heart Foundation

IntroductionThe influence of unfractionated heparin (UFH) and other anticoagulants on the spread of cancer has been reported since the early 1960s.1 However, clinical studies investigating the use of heparins in cancer patients have not produced consistent results.2 Intravenous, adjusted-dose UFH for 5 to 10 days has been the standard initial treatment for venous thrombosis. More recently, subcutaneous, fixed-dose, low molecular weight heparins (LMWHs), which are fractions of the parent compound, have been shown to be safe and effective alternatives to UFH in the initial treatment for venous thromboembolism.3-5 In one of our randomized clinical trials comparing LMWH and UFH in the initial treatment of deep vein thrombosis (DVT), we observed an unexpected difference in 6-month mortality among cancer patients in favor of LMWH, which could not be attributed to a difference in the incidence of thrombotic or bleeding complications.6 A similar observation in favor of LMWH was reported in a subsequent study and in a meta-analysis of trials.7,8 The number of cancer patients included in these studies was small, and adjustment of the observed effect for the baseline characteristics of the cancer patients was not possible. However, these findings suggested an inhibitory effect of LMWH on tumor growth or metastasis, which is less apparent or absent for UFH, resulting in a beneficial effect on the survival of cancer patients. This hypothesis is supported by the observations, in experimental studies, that LMWH and low molecular weight heparan sulfate, in comparison to UFH, effectively suppressed angiogenesis, a process necessary for tumor growth and metastasis.9,10 On the other hand, animal studies that investigated the effect of chemically-modified heparins on the spread of cancer did not detect a superior anti-tumor effect of LMWH compared to UFH; both were found to inhibit metastasis.11,12 To date, the effect of LMWH on cancer survival in humans has not been investigated as a primary objective. If a consistent and beneficial effect of LMWH on mortality is indeed present, such a study would be warranted.We performed a meta-analysis of all available randomized clinical trials where LMWH was compared with UFH in the treatment of venous thromboembolism (VTE) to estimate the crude treatment effect of LMWH on mortality in cancer patients compared to UFH. Subsequently, we adjusted this treatment effect for age, gender, and primary malignancy site by reanalyzing data from three of those trials.3-5 This effect was further adjusted for other prognostic factors, including cancer histology, tumor stage, presence of metastases, duration of cancer, and concomitant use of cancer treatment, by analyzing individual patient data from the largest randomized trial.5

Summary Introduction: Since the introduction of low-molecular-weight heparins (LMWHs) in the early 1980's, the use of these compounds has been extensively investigated as a substitute for unfractionated heparin (UFH) in patients with venous and arterial thrombotic diseases. LMWHs have several advantages as compared to UFH, such as the subcutaneous route of administration, the predictable anticoagulant response and the lack of the need for laboratory monitoring. The present systematic review evaluates randomised clinical trials which investigated the efficacy and safety of LMWH in the acute treatment of venous thromboembolims, myocardial infarction, unstable coronary syndromes and ischemic stroke. Methods: A computerised and manual search was performed to identify all relevant clinical trials. All randomised studies, with an a priori defined study population, clinical outcome measurement and adequate follow-up, were reviewed by two independent assessors. Whenever possible a common effect estimate of the included studies was calculated. Results: Thirteen studies in approximately 4000 patients with acute venous thromboembolism revealed an odds ratio for the 3-month recurrent thromboembolism rate and major bleeding complications during exposure of 0.77 (C.I. 0.57-1.04) and 0.61 (C.I. 0.39-0.95), respectively, in favour of LMWH as compared to UFH. In patients with acute myocardial infarction, one study suggested a reduction in the incidence of reinfarction and cardiac death in LMWH recipients compared to UFH, while a placebo-controlled study revealed no beneficial effect of LMWH on these outcomes. In six studies including over 7000 patients with acute unstable coronary syndromes, there was an odds ratio for recurrent angina, myocardial infarction, urgent revascularisation and major bleedings of 0.88 (C.I. 0.76-1.01), 0.84 (C.I. 0.69-1.01), 0.83 (C.I. 0.70-0.99), 1.09 (C.I. 0.70-1.70), respectively, in favour of LMWH compared to UFH. The three studies comparing LMWH treatment with placebo in approximately 1000 patients with acute ischemic stroke revealed an odds ratio for the 10-day recurrent stroke, death or disability after 3 months and major bleeding complications of 0.68 (C.I. 0.41-1.13), 0.94 (C.I. 0.78-1.15), 2.92 (C.I. 1.88-4.55), respectively. Conclusion: Fixed-dose subcutaneous LMWH appears to be a safe and effective alternative for dose-adjusted intravenous heparin in the treatment of patients with acute venous thrombotic disease as well as in patients with acute unstable coronary syndromes. The effectiveness of LMWH in patients with acute myocardial infarction remains unclear. There seems to be no beneficial effect of LMWH treatment as compared to placebo in patients with acute ischemic stroke, while the risk of major bleeding was clearly increased.

In this review, we analyze data from randomized trials in which low molecular weight heparin was compared with unfractionated heparin, both to estimate the treatment effect of low molecular weight heparin in the initial treatment of venous thromboembolism and to evaluate the effect of the varied proportion of included cancer patients (6% to 22.7%) on the incidence of outcome events (recurrence of venous thromboembolism, bleeding, and mortality) and on the estimated treatment effect. Low molecular weight heparin has been extensively investigated in patients with deep vein thrombosis, but few trials have included patients with pulmonary embolism. The risk of recurrence of venous thromboembolism (odds ratio, 0.77; 95% CI, 0.56-1.04), major bleeding (odds ratio, 0.60; 95% CI, 0.38-0.95), and mortality (odds ratio, 0.72; 95% CI, 0.55-0.96) was less with low molecular weight heparins compared with unfractionated heparin. The proportion of cancer patients in these studies had a statistically significant effect on the incidence of recurrent venous thromboembolism (P = 0.03) and mortality (P = 0.002), but no influence on the estimated treatment effects of low molecular weight heparins. Low molecular weight heparin is effective and safe in the initial treatment of venous thromboembolism.

BACKGROUND The reported incidence of a subsequent diagnosis of malignancy in patients presenting with deep vein thrombosis (DVT) varies from 2-25%. Risk indicators and diagnostic procedures to be performed in these patients are controversial. METHODS Four hundred consecutive patients with confirmed DVT included in a randomized clinical trial were followed prospectively for 6 months. The incidence of a subsequent diagnosis of malignancy was calculated and compared between patients with unexplained DVT and patients with secondary DVT. Potential risk indicators for subsequent malignant disease were evaluated. RESULTS Of the 400 patients, 70 already had been diagnosed with malignancy; another four patients were lost to follow-up. Of the remaining 326 patients, 10 new malignancies were diagnosed among 137 patients with unexplained DVT (7.3%) and 3 new malignancies were diagnosed in 189 patients with secondary DVT (1.6%). The relative risk was 4.6 (95% confidence interval, 1.3-16; P = 0.009). Age, gender, or location of the DVT had no significant effect on the incidence of diagnosis when adjusted for unexplained DVT. Ten of these 13 patients (77%) had abnormal clinical findings suggestive of malignancy at the time of presentation with DVT. CONCLUSIONS Unexplained DVT is a significant risk indicator of underlying malignancy. The majority of patients with undiagnosed malignancy have some clinical abnormality suggestive of underlying malignancy at the time of presentation with unexplained DVT. A simple clinical evaluation comprised of medical history, physical examination, routine laboratory tests, and chest X-ray can detect such patients. Extensive screening of all patients presenting with unexplained DVT does not appear to be justified. Cancer 1998;83:180-185. © 1998 American Cancer Society.

Background Low-molecular-weight heparin is known to be safe and effective for the initial Treatment of patients with proximal deep-vein thrombosis. However, its application to patients with pulmonary embolism or previous episodes of thromboembolism has not been studied.Methods We randomly assigned 1021 patients with symptomatic venous thromboembolism to fixed-dose, subcutaneous low-molecular-weight heparin (reviparin sodium) or adjusted-dose, intravenous unfractionated heparin. Oral anticoagulant therapy with a coumarin derivative was started concomitantly and continued for 12 weeks, Approximately one third of the patients had associated pulmonary embolism, The outcome events studied over the 12 weeks were symptomatic recurrent venous thromboembolism, major bleeding, and death. We sought to determine whether low-molecular-weight heparin is at least equivalent to unfractionated heparin in patients with venous thromboembolism.Results Twenty-seven of the 510 patients assigned to low-molecular-weight heparin (5.3 percent) had recurrent thromboembolic events, as compared with 25 of the 511 patients assigned to unfractionated heparin (4.9 percent). The difference of 0.4 percentage point indicates that the two therapies have equivalent value according to our predetermined definition of equivalence. Sixteen patients assigned to low-molecular-weight heparin (3.1 percent) and 12 patients assigned to unfractionated heparin (2.3 percent) had episodes of major bleeding (P=0.63), and the mortality rates in the two groups were 7.1 percent and 7.6 percent, respectively (P=0.89).Conclusions Fixed-dose, subcutaneous low-molecular-weight heparin is as effective and safe as adjusted-dose, intravenous unfractionated heparin for the initial management of venous thromboembolism, regardless of whether the patient has pulmonary embolism or a history of venous thromboembolism. (C) 1997, Massachusetts Medical Society.

The incidence of newly diagnosed malignancy is increased in patients with unexplained venous thromboembolism during the first year after a thromboembolic event in comparison to controls (odds ratio, 3.9-36). Extensive screening with computed tomography, endoscopy and tumor markers can identify most of these undetected malignancies. However, approximately half of these can also be identified based on a simple clinical evaluation. Extensive screening has no demonstrated benefit and might actually cause harm. This consideration, combined with the economical and psychological costs of extensive screening leads to the decision not to use such screening procedures, unless indicated by clinical circumstances. Thus, it is appropriate to maintain a low threshold of suspicion for malignancy when treating patients with unexplained venous thromboembolism and to base the decision to perform additional diagnostic tests on the findings of an initial medical history, physical examination, routine laboratory tests and chest x-ray.

The concern for the environment is ever growing and counter measures are also taken by manycountries to minimize environmental impacts arising from developmental activities. One tool utilised toensure that developments are sustainable is Environmental Impact Assessment (EIA) which hasbeen a mandatory requirement in Sri Lanka since 1993. However, due to considerable time taken bythe EIA process particularly for extensive projects such as road sector projects concerns have beenraised as to the delays caused by the process which in certain instances might even cause loss offoreign funds. Although detailed assessments are required in some cases it is not always true. Roadrehabilitation projects do not fall into the category of prescribed projects of the National EnvironmentalAct unless sensitive areas are involved and resettlement of more than 100 families are involved.However, foreign funding agencies generally require an environmental assessment of even suchprojects prior to approving of funding which generally cause delays since environmental assessorstend to follow tile same pattern of assessment for all projects regardless of the scope. Numerousmethods have evolved over the years to conduct EIAs some ct'which address environmental impact assessment of sectoral projects particularly water resource development projects which are ratherconvenient to use. However thus far such methods have not been developed for road sector projects. The present study was conducted to develop a Rapid Environment Assessment (REA) technique forthe Sri Lankan road rehabilitation projects where such a tool is yet to immerge. The REA was designedfrom the information collected from literature survey, questionnaire surveys of affected communities,field observations and subject experts' interviews. Three actual rehabilitation projects were studiedfor this purpose. Based on the information first the activities relevant to all the road rehabilitationprojects were listed with the assistance received from the field engineers. Then those activities whichhave no significant impacts were taken out keeping only the activities causing impacts forconsideration.The designed tool in this study is armed with both primary and secondary impacts whichcan arise from specific activities of road rehabilitation projects as well with proposed mitigatory measureswhich can minimize these impacts. The REA is not only comprehensive but also user friendly asactivities and impacts are predetermined and linked to each other so that the users do not have toprepare their own checklists of activities or environmental aspects. It's handy and small. It's generalin usage and could be used in any site of road rehabilitation projects. It's concise as only those activitieswith significant impacts are chosen and included. From surveys it was also discovered that to avoid unnecessary oppositions and social commotion,which would hinder the rehabilitation projects compensation should be decided and granted at theplanning stage itself. It is also highly recommended that a strong monitoring system is utilized. If anyof the proposed mitigatory measures is not effective in neutralizing the impacts, a search for newmeasures is recommended and REA is to be updated accordingly. As REA is not available for roadrehabilitation projects at present in Sri Lanka the tool designed in my study could be taken for futureroad rehabilitation projects to minimize the disadvantages of ElA. However, it should note that theREA is to be used only by experts in order to be effective and accurate.

Bioethanol production in North America has led to the production of considerable quantities of different co-products. Variation in nutrient profiles as well as nutrient availability among these co-products may lead to the formulation of imbalanced diets that may adversely affect animal performance. This study aimed to compare three types of dried distiller's grains with solubles [100% wheat DDGS (WDDGS); DDGS blend1 (BDDGS1, corn to wheat ratio 30:70); DDGS blend2 (BDDGS2, corn to wheat ratio 50:50)] and their different batches within DDGS type with regard to: (i) protein and carbohydrate sub-fractions based on Cornell Net Carbohydrate and Protein System (CNCPS); (ii) calculated energy values; and (iii) rumen degradation of dry matter (DDM), organic matter (DOM), crude protein (DCP), neutral detergent fibre (DNDF) and starch (Dstarch) at 36 and 72 h of ruminal incubations. Wheat DDGS had a lower intermediately (PB2, 136.4 vs. 187.4 g/kg DM) and a higher slowly degradable true protein (PB3, 142.2 vs.105.3 g/kg DM) than BDDGS1, but similar to those of BDDGS2. Sugar (CA4) was higher, whereas starch (PB1) and digestible fibre (PB3) were lower in WDDGS than in BDDGS1 and BDDGS2. All carbohydrate sub-fractions determined differed significantly between the two batches of BDDGS2. The BDDGS2 had the highest calculated energy values (TDN, DE(3×) , ME(3×) , NEL(3×) , NE(m) and NE(g) ) among the three DDGS types. The energy values were slightly different between the batches of the three DDGS types. At all incubation times, wheat DDGS had a significantly higher (p0.05) DDM, DOM, DCP and DNDF than both DDGS blends. Differences were observed between different batches within DDGS types with regard to in situ rumen degradation of DM, OM, CP, NDF and starch. In conclusion, differences were observed in protein and carbohydrate sub-fractions and in situ ruminal degradation of DM, OM, CP, NDF and starch among the three DDGS types and different batches within DDGS type. This indicates that the nutrients supplied to ruminants may not only differ among different types of DDGS but it may also differ among different batches within DDGS type.

Congenital mesoblastic nephroma (CMN) first described by Bolande et al in 1967 [1] is the commonest neonatal tumour of renal origin comprising of 3-10% of all childhood tumours [2]. Common modes of presentation include abdominal mass, antenatal diagnosis and features of para-neoplastic syndrome [3]. There are two main histological varieties; classic type where nephroureterectomy is curative and atypical (cellular) type with unpredictable natural history [2,4].

Lipid-encapsulated microbubbles have demonstrated utility in biomedical applications as ultrasound contrast agents and drug delivery vehicles. Current production methods of these microbubbles result in distributions with a large size variance. The size and monodispersity of ultrasound contrast agents are fundamentally important due to the relationship between bubble diameter and resonant frequency, destruction threshold, and susceptibility to radiation force. Several groups have recently developed microfluidic technologies for generation of microbubbles, but to date no group has demonstrated the production of shell-stabilized monodisperse contrast agents using these techniques. In this work, we use microfluidic-based flow focusing methods to produce monodisperse microbubbles in the diameter range required for in-vivo imaging. The diameter of the bubbles produced using this technique can be precisely tailored by adjusting the gas and liquid flow rate parameters. In order to stabilize the microbubbles for use as ultrasound contrast agents, we examine aqueous mixtures of glycerol/propylene glycol as well as stabilizing lipids. The effect of the lipid, emulsifier and viscosity agent concentration was found to be critical to stabilize the microbubbles. High-speed camera images and particle sizing analysis were combined to study the coalescence and dissolution phenomena as well as the size distribution. The concentration of the PEG-emulsifier and the existence of the viscosity agents determined the microbubble coalescence rate. Our experiments show that an optimum concentration of glycerol and propylene glycol in the liquid phase mixture reduces coalescence. Monodisperse microbubbles coated with a lipid-shell in a viscous solution were found to be stable up to three months

This paper describes a pharmacokinetic study performed in Sprague-Dawley rats after i.v. administration of a single 6-mg/kg dose of 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane (Altropane). Plasma samples were collected from the retro-orbital sinus at times up to 3 h after drug administration, extracted by solid-phase extraction, and the drug levels determined by capillary electrophoresis (CE). Pharmacokinetic parameters were determined by a standard noncompartmental model using WinNonlin version 1.5. The maximum plasma concentrations, clearances of the drug, and areas under the curve for male and female rats were 5.74 and 7.26 microg/ml, 135.7 and 98.5 ml/kg x min, and 44.23 and 60.92 microg x min/ml, respectively. The drug was cleared very rapidly from the systemic circulation, with a terminal t(1/2) of 7 to 10 min and a mean residence time of about 11 min for both sexes. The volume of distribution was approximately 1 l/kg. No metabolites were detected when the samples were analyzed individually. However, after samples were pooled and concentrated, traces of two unknown peaks that may represent metabolites were detected in concentrates from the last two timepoints. Part I of this work [J. Chromatogr. A, 895 (2000) 87] describes validation of CE methods for the analysis of aqueous and plasma samples of Altropane, including its solid-phase extraction from rat plasma.

Among the many opioid peptides developed to date as nonaddictive analgesics, biphalin has exhibited extraordinary high potency and many other desirable characteristics. Biphalin is an octapeptide consisting of two monomers of a modified enkephalin, attached via a hydrazine bridge, and with the amino acids assembled in a palindromic sequence. Its structure is (Tyr-D-Ala-Gly-Phe-NH-)-2. However, this unique peptide, like any other synthetic peptide, needs strict quality control because of certain drawbacks associated with peptide synthesis. This paper discusses our approaches to characterizing and analyzing biphalin. Many techniques were used, including elemental analysis, amino acid analysis, amino acid sequence analysis (AASA), mass spectrometry (MS), 1H-NMR, 1H-correlated spectroscopy (COSY)-NMR, high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Electrospray ionization (ESI) mass spectrometry, which included both ESI-MS and ESI-MS/MS, was performed to confirm the full sequence because AASA results alone verified only the monomer sequence, and not the full sequence. Although the 1H-NMR results led to a preliminary assignment of many protons, the 1H COSY-NMR results allowed for unequivocal assignment of almost all protons. Peptide purity was determined using two techniques, reversed-phase HPLC and CE. The counter-ion of the peptide, trifluoroacetic acid, was determined by CE, using an indirect detection method developed previously in our laboratory. This paper illustrates successful application of nonconventional techniques to characterize and analyze a structurally modified peptide, biphalin, when standard techniques for peptide analysis are inadequate.

Altropane, 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(3-iodo-E-allyl)nor tropane, is an imaging agent that was developed recently for early detection of Parkinson's disease. Its promise as a useful radiopharmaceutical for single-photon emission computed tomography or positron emission tomography imaging of the brain has been well demonstrated, and it is currently undergoing clinical trials. This paper presents methods development and validation of capillary electrophoresis (CE) techniques to analyze Altropane in aqueous environments as well as in rat plasma, using an internal standard, nicotinamide. N-Allylaltropane, 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-allylnortropane, which is a known degradation product of the Altropane precursor (tributyltinaltropane), was used to verify the method's specificity. A solid-phase extraction method for extraction of Altropane from rat plasma is also described. The results presented in this paper demonstrate the applicability of CE methods to study the pharmacokinetic properties of Altropane in animal models. The results of the pharmacokinetic study will be published later, as Part II.

Background There is no consensus on the efficacy of physical training, smoking cessation, and pharmacological therapy (pentoxifylline or nafronyl oxalate) in the treatment of patients with intermittent claudication at Fontaine stage II of disease. Methods A MEDLINE and manual search was used to identify relevant publications. Uncontrolled or retrospective studies, double reports, and trials without clinically meaningful outcomes were excluded. Included studies were graded level 1 (randomized and double- or assessor-blind), level 2 (open randomized), or level 3 (nonrandomized). Pain-free and total walking distance were the main outcomes considered; when feasible, end-of-treatment results were combined with appropriate meta-analytical procedures. Results In 5 level 2 studies, physical training increased pain-free and total walking distance significantly (139.0 m [95% confidence interval {CI}, 31.0 to 246.9 m] and 179.1 m [95% CI, 60.2 to 298.1 m], respectively). In a level 3 study, smoking cessation resulted in a nonsignificant increase in total walking distance of 46.7 m (95% CI, −19.3 to 112.7 m). In 6 level 1 studies, pentoxifylline increased both pain-free and total walking distance by 21.0 m (95% CI, 0.7 to 41.3 m) and 43.8 m (95% CI, 14.1 to 73.6 m), respectively. In 4 level 1 trials, nafronyl significantly increased pain-free walking distance (58.6 m [95% CI, 30.4 to 86.8 m]) and total walking distance (71.2 m [95% CI, 13.3 to 129.0 m]). Conclusions Physical training increased pain-free and total walking distance in level 2 studies. Only level 3 studies support the usefulness of smoking cessation. In level 1 studies, pentoxifylline and nafronyl increased pain-free and total walking distance, but the average effects were relatively small.

Summary Background. There is no consensus on the efficacy of the antithrombotic drugs available for patients with intermittent claudication. Methods. A Medline and manual search was used to identify relevant publications. Uncontrolled or retrospective studies, double reports or trials without clinical outcomes were excluded. Included studies were graded as level 1 (randomised and double- or assessor-blind), level 2 (open randomised), or level 3 (non-randomised comparative). Mortality, cerebro- or cardiovascular events, amputations, arterial occlusions or number of revascularization procedures performed in the lower limbs, pain-free and total walking distance, ankle brachial index and calf blood flow, were the main outcomes considered. When feasible, end of treatment results, either continuous or binary, were combined with appropriate statistical methods. Results. Mortality was significantly decreased by ticlopidine compared to placebo (common odds ratio 0.68, 95% C.I., 0.49 - 0.95); clopidogrel decreased vascular events in comparison to aspirin (odds ratio 0.76, 95% C.I., 0.63 - 0.92) in level 1 studies. Arterial occlusions and the number of revascularization procedures performed were statistically significantly decreased by aspirin and ticlopidine, respectively. A small but statistically significant improvement in pain-free walking distance was determined by picotamide, indobufen, low molecular weight heparins, sulodexide and defibrotide, in small studies. Conclusions. Clopidogrel and ticlopidine do reduce clinically important events in patients with intermittent claudication and could be added to the primary medical treatment of these patients. The use of aspirin in these patients cannot be based on direct evidence, but only on analogy with coronary and cerebral atherosclerosis, where it has documented efficacy. Other antithrombotic drugs were not properly evaluated in patients with intermittent claudication.