Malaysian consensus statement on FDG PET-CT reporting format for lymphoma.

Over the past decade, 18F-Fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PETCT) has emerged as an important imaging modality in the management of lymphoma. Since the introduction of Deauville scoring system (2009) and the Lymphoma Response Assessment Criteria (2014), clinicians are now sharing a common language in the management of lymphoma. In Malaysia, nearly a third of PET-CT request is related to lymphoma imaging. Though there are extensive publications regarding these scoring systems and assessment criteria for lymphoma, there are hardly any literature on the reporting format for the 18F-FDG PET-CT in this disease. The variable reporting formats have on many occasions caused confusion not only to the referring clinicians but also to nuclear medicine physicians. Thus, a working committee comprising experienced nuclear medicine physicians and haematologists in Malaysia have agreed and made a joint recommendation on the standard reporting format for 18F-FDG PET-CT in Lymphoma. This recommendation will minimize inter-observer discrepancies in reporting, facilitate the understanding of the report of the referring clinicians as well as facilitate counseling between patients and clinicians in the management of the disease.

Application of 18F-FDG PET-CT in the management of pulmonary nodule and mass - a pictorial review.

BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide. Pulmonary nodules are commonly encountered in clinical practice because of the recent implementation of low-dose CT lung screening programme, incidental finding on cardiac CT or CT for nonthoracic related disease. 18F-FDG PET-CT plays an important role in the management of pulmonary nodules. METHODS: In this pictorial review, we present six different scenarios of using 18F-FDG PET-CT in the management of suspicious pulmonary nodule or mass. The advantages and limitations of 18F-FDG PET-CT and Herder model are discussed. RESULTS: 18F-FDG PET-CT with risk assessment using Herder model provides added value in characterising indeterminate pulmonary nodules. Besides, 18F-FDG PET-CT is valuable to guide the site of biopsy and provide accurate staging of lung cancer. CONCLUSION: To further improve its diagnostic accuracy, careful history taking, and CT morphological evaluation should be taken into consideration when interpreting 18FFDG PET-CT findings in patients with these nodules.

The Cuffless Blood Pressure Measurement with Multi-dimension Regression Model based on Characteristics of Pulse Waveform.

According to the advancement of wearable technology, many physiological monitoring instruments are gradually converted into wearable devices. But, the blood pressure monitor still is a cuff-type device in the consumer market, which also does not do the beat-by-beat continuous blood pressure measurement. Now, the cuffless blood pressure measurement has been developed based on the pulse transit time (PTT) but its accuracy is not better. According to the cardiac hemodynamic theorem, the blood pressure relates with the arterial characteristics. Therefore, the purpose of this study was to use the characteristics of the pulse wave measured by photoplethysmography (PPG) to estimate the blood pressure with a multi-dimension regression model. The contour of pulse wave includes some characteristics of the artery. There were 10 subjects participating the experiment, and the blood pressure of the subject was changed by the exercise. The results showed that the cumulate root mean square error of the estimated systolic and diastolic pressures with the multi-parameters were 69.3 mmHg and 39.8 mmHg were better than only using one parameter, PTT, 82.1 mmHg and 45.2 mmHg, respectively.

Features of post-radioiodine whole body scan in non-invasive Follicular Thyroid Neoplasm with papillary-like nuclear features (NIFTP).

Recently, encapsulated follicular variant of papillary thyroid carcinoma has been reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) to emphasize the benign nature of this entity. In our institution, we have assessed 455 patients treated with radioiodine ablation for differentiated thyroid carcinoma and 20 of them were retrospectively found to fulfill the new NIFTP criteria. There was no evidence of metastasis on post radioiodine whole body scans for NIFTP cases and these patients were in remission subsequently. The benign features of these patients' whole body scans and good clinical outcome following treatment further support NIFTP as a low risk thyroid neoplasm.

Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration.

Vaccinia H1-related phosphatase (VHR/DUSP3) is a member of the dual-specificity phosphatase family. Deregulation of VHR is observed in various malignant diseases. We identified focal adhesion kinase (FAK) as a VHR-interacting molecule. Over-expression of VHR decreased tyrosine phosphorylation of FAK and decreasing VHR promoted FAK tyrosine phosphorylation. In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin. VHR-knockout mice did not have obvious abnormality; however, VHR-knockout cells showed decreased expression of integrins and FAK but stronger FAK and paxillin phosphorylation upon attachment to fibronectin. Additionally, VHR-knockout fibroblast and lung epithelial cells had elevated ligand-induced epidermal growth factor receptor (EGFR) phosphorylation. Inducible expression of VHR suppressed directional cell migration, and VHR deficiency resulted in a higher cell migratory ability. VHR-knockout cells have stronger FAK phosphorylation in cell adhesions, long-lasting trailing ends and slower turnover of focal adhesions. These collective data indicate that VHR is a FAK phosphatase and participates in regulating the formation and disassembly of focal adhesions.

Prevalence and Antimicrobial Susceptibility of Vibrio parahaemolyticus Isolated from Short Mackerels (Rastrelliger brachysoma) in Malaysia.

Numerous prevalence studies and outbreaks of Vibrio parahaemolyticus infection have been extensively reported in shellfish and crustaceans. Information on the quantitative detection of V. parahaemolyticus in finfish species is limited. In this study, short mackerels (Rastrelliger brachysoma) obtained from different retail marketplaces were monitored with the presence of total and pathogenic strains of V. parahaemolyticus. Out of 130 short mackerel samples, 116 (89.2%) were detected with the presence of total V. parahaemolyticus and microbial loads of total V. parahaemolyticus ranging from <3 to >105 MPN/g. Prevalence of total V. parahaemolyticus was found highest in wet markets (95.2%) followed by minimarkets (89.1%) and hypermarkets (83.3%). Pathogenic V. parahaemolyticus strains (tdh+ and/or trh+) were detected in 16.2% (21 of 130) of short mackerel samples. The density of tdh+ V. parahaemolyticus strains were examined ranging from 3.6 to >105 MPN/g and microbial loads of V. parahaemolyticus strains positive for both tdh and trh were found ranging from 300 to 740 MPN/g. On the other hand, antibiotic susceptibility profiles of V. parahaemolyticus strains isolated from short mackerels were determined through disc diffusion method in this study. Assessment of antimicrobial susceptibility profile of V. parahaemolyticus revealed majority of the isolates were highly susceptible to ampicillin sulbactam, meropenem, ceftazidime, and imipenem, but resistant to penicillin G and ampicillin. Two isolates (2.99%) exhibited the highest multiple antibiotic resistance (MAR) index value of 0.41 which shown resistance to 7 antibiotics. Results of the present study demonstrated that the occurrence of pathogenic V. parahaemolyticus strains in short mackerels and multidrug resistance of V. parahaemolyticus isolates could be a potential public health concerns to the consumer. Furthermore, prevalence data attained from the current study can be further used to develop a microbial risk assessment model to estimate health risks associated with the consumption of short mackerels contaminated with pathogenic V. parahaemolyticus.

p38 MAP kinase interacts with and stabilizes pancreatic and duodenal homeobox-1.

Pancreatic and duodenal homeobox-1 (PDX-1) is a homeodomain-containing transcription factor that plays a critical role in pancreatic development, ß-cell differentiation, maintenance of normal ß-cell function and tumorigenesis. PDX-1 is subjected to extensive post-translational modifications for its stability, subcellular location and transactivity. We report here that PDX-1 expression is up-regulated by p38 MAP kinase. Antibody array screen identified p38 as a candidate PDX-1-interacting protein in GFP-PDX-1 stable HEK293 cells. The p38-PDX-1 interaction was confirmed by immunoprecipitation/Western blotting analysis in both transient transfection system of HEK293 cells and endogenous system of ß-TC-6 cells stimulated by glucagon-like peptide 1 (GLP-1). Co-transfection of p38 with PDX-1 resulted in increased PDX-1 expression in HEK293 cells, which was accompanied by a decreased PDX-1 ubiquitination. Mass spectrometry analysis showed that Ser 268 of human PDX-1 was phosphorylated in GFP-PDX-1 stable HEK293 cells. Functional mutagenesis analysis showed that mutation of Ser 269 of mouse PDX-1 (corresponding to Ser 268 of human PDX-1) into nonphosphorylatable alanine abolished the stabilizing effect of p38 on PDX-1, which was in line with enhanced PDX-1 ubiquitination and shortened half-life of PDX-1. p38 showed kinase activity towards PDX-1 in vitro, suggesting that Ser 269 is a potential p38-regulated phosphorylation site within PDX-1. GLP-1-stimulated PDX-1 expression was accompanied by p38 kinase activation in mouse insulinoma ß-TC-6 cells and p38 inhibitor SB202190 inhibited GLP-1-stimulated PDX-1 expression with accompanied inhibition of p38 kinase activation. Taken together, our studies indicated that p38 MAP kinase is a positive regulator of PDX-1 stability and that p38 exerts its stabilizing effect on PDX-1 through a phosphorylation-dependent inhibition of PDX-1 ubiquitination.

The role of genetics and environment in the rise of childhood food allergy.

Food allergy is a growing clinical and public health problem world-wide. The rising incidence is occurring more rapidly than changes to the genome sequence would allow, but it is yet to be determined whether environmental factors might act in interaction with genetic risk. That is to say, are environmental factors more likely to affect those genetically at risk? Family history is a strong risk factor for the development of food allergy as it co-aggregates with other atopic diseases and as such genetic factors do play an important role in food allergy risk. However, significant interest has now turned to the role of epigenetic modifications of the genome as the major mediator of gene-environment interaction. The consideration of the role of epigenetics in food allergy is likely to provide an insight into aetiological and biological disease mechanisms. This paper discusses the current state of knowledge regarding genetic and environmental risk factors for food allergy, and considers the potential for furthering our understanding of food allergy aetiology by examining the role of epigenetic variation.

Loeys-Dietz syndrome: a Marfan-like syndrome associated with aggressive vasculopathy.

Loeys-Dietz syndrome is a recently-characterised genetic disorder with an autosomal-dominant inheritance due to mutations in the transforming growth factor beta-receptor Type 1 or Type 2 genes. We present a Chinese female neonate with genetically-confirmed Loeys-Dietz syndrome, cleft palate, hypertelorism, and an early dilatation of the aortic root and ascending aorta. This syndrome is associated with an aggressive arteriopathy, with an increased risk of dissection and rupture. Early diagnosis, close monitoring and early surgery may prolong the life in affected individuals. Losartan is an emerging therapy that may help slow down the rate of arterial dilatation.

Ranibizumab treatment for neovascular age-related macular degeneration: from randomized trials to clinical practice.

BACKGROUND: Although randomized clinical trials (ANCHOR and MARINA) have shown excellent results of ranibizumab treatment in patients with neovascular age-related macular degeneration (AMD), it is unclear whether such an outcome is achievable in daily practice. We evaluated the results of ranibizumab treatment for neovascular AMD in clinical practice in Australia. METHODS: A retrospective chart review of patients in four practices injected with ranibizumab in 2006 for AMD. Patients who had been diagnosed with subfoveal choroidal neovascular membrane in the preceding 6 months and had completed at least 6 months follow-up were enrolled. No standard treatment protocols were required. The main outcome measure was visual acuity (VA) at 6 and 12 months. RESULTS: A total of 158 patients fulfilled the entry criteria. The mean baseline VA (decimal) was 0.35+/-0.21 (Snellen equivalent 6/17). At 6 months, the mean VA improved to 0.46+/-0.27 (6/13) and remained stable until month 12 (0.48+/-0.30). The improvement in VA between baseline and months 6 and 12 was statistically significant (P<0.0001). Both the mean and the median number of injections were four in the first 6 months and nine at 12 months. VA results were comparable with those of the ANCHOR and MARINA trials, and were achieved with a lower number of injections (P<0.0001). CONCLUSION: VA results achieved in daily clinical practice using ranibizumab for neovascular AMD are similar to large prospective randomized trials.

Development and trends of biosurfactant analysis and purification using rhamnolipids as an example.

During the last few decades, increasing interest in biological surfactants led to an intensification of research for the cost-efficient production of biosurfactants compared with traditional petrochemical surface-active components. The quest for alternative production strains also is associated with new demands on biosurfactant analysis. The present paper gives an overview of existing analytical methods, based on the example of rhamnolipids. The methods reviewed range from simple colorimetric testing to sophisticated chromatographic separation coupled with detection systems like mass spectrometry, by means of which detailed structural information is obtained. High-performance liquid chromatography (HPLC) coupled with mass spectrometry currently presents the most precise method for rhamnolipid identification and quantification. Suitable approaches to accelerate rhamnolipid quantification for better control of biosurfactant production are HPLC analysis directly from culture broth by adding an internal standard or Fourier transform infrared attenuated total reflectance spectroscopy measurements of culture broth as a possible quasi-online quantification method in the future. The search for alternative rhamnolipid-producing strains makes a structure analysis and constant adaptation of the existing quantification methods necessary. Therefore, simple colorimetric tests based on whole rhamnolipid content can be useful for strain and medium screening. Furthermore, rhamnolipid purification from a fermentation broth will be considered depending on the following application.

Homopolymeric pyrrolidine-amide oligonucleotide mimics: Fmoc-synthesis and DNA/RNA binding properties.

By chemically modifying or replacing the backbone of oligonucleotides it is possible to modulate the DNA and RNA recognition properties and fine-tune the physiochemical properties of oligomers. This is important because it challenges our understanding of natural nucleic acid structural and recognition properties and can lead to nucleic acid mimics with a wide range of applications in nucleic acid targeting, analysis or diagnostics. In this paper we describe the solid phase synthesis of pyrrolidine-amide oligonucleotide mimics (POMs) using Fmoc-peptide chemistry. This required the synthesis of adeninyl, cytosinyl, thyminyl and guaninyl pyrrolidine monomers, with Fmoc- and standard acyl-protecting groups on the exocyclic amino groups and nucleobases respectively. These monomers were used to synthesise several thyminyl and adeninyl POM pentamers, with modest coupling efficiency. The pentamers were purified by RP-HPLC, characterised by mass spectrometry and their DNA and RNA binding properties were investigated using UV thermal denaturation/renaturation experiments. This revealed that all the pentamers exhibit strong affinity for complementary nucleic acids. The further evaluation of longer mixed-sequence POMs is described in a second accompanying paper (R. J. Worthington et al., Org. Biomol. Chem., 2006, DOI: 10.1039/b613386j).

Mixed-sequence pyrrolidine-amide oligonucleotide mimics: Boc(Z) synthesis and DNA/RNA binding properties.

Pyrrolidine-amide oligonucleotide mimics (POMs) exhibit promising properties for potential applications, including in vivo DNA and RNA targeting, diagnostics and bioanalysis. Before POMs can be evaluated in these applications it is first necessary to synthesise and establish the properties of fully modified oligomers, with biologically relevant mixed sequences. Accordingly, Boc-Z-protected thyminyl, adeninyl and cytosinyl POM monomers were prepared and used in the first successful solid phase synthesis of a mixed sequence POM, Lys-TCACAACTT-NH2. UV thermal denaturation studies revealed that the POM oligomer is capable of hybridising with sequence selectivity to both complementary parallel and antiparallel RNA and DNA strands. Whilst the duplex melting temperatures (Tm) were higher than the corresponding duplexes formed with isosequential PNA, DNA and RNA oligomers the rates of association/dissociation of the mixed sequence POM with DNA/RNA targets were noticeably slower.

Stereospecific backbone methylation of pyrrolidine-amide oligonucleotide mimics (POM).

The introduction of (7'S)-methyl groups into the backbone of pyrrolidine-amide oligonucleotide mimics (POM) does not interfere with high affinity recognition of complementary nucleic acids, whereas (7'R)-methylation disrupts hybridisation significantly.

Infective endocarditis in childhood: a seven-year experience.

INTRODUCTION: The epidemiology, clinical features, treatment and outcomes of infective endocarditis (IE) are reviewed. METHODS: A retrospective descriptive study was performed involving patients treated for IE at a paediatric tertiary centre in Singapore, between May 1997 and April 2004. Duke criteria were used to retrospectively evaluate the diagnosis of IE in these cases. Data analysis was performed using SPSS for Windows. RESULTS: There were a total of 27 children with IE in the seven-year study period. Of these, 24 (88.9 percent) had congenital heart disease, one had rheumatic valvular heart disease and two had normal anatomy. Fever (81.5 percent) was the primary presenting symptom, while splenomegaly (40.7 percent) and septic spots (22.2 percent) were the most common physical findings. C-reactive protein was raised in all cases with a mean of 100.1mg/L. Blood cultures were positive in 77.8 percent of cases and the most common organism identified was Viridans Streptococcus species (25.9 percent). Vegetations were detected on echocardiography in 55.5 percent of cases. According to the Duke criteria, 48.1 percent of our patients fulfilled the clinical diagnosis of definite IE and 51.9 percent had possible IE. The median duration of parenteral antibiotics was 31 days. Major complications were seen in seven (25.9 percent) patients, of whom five had either left heart vegetations or a right-to-left shunt physiology. CONCLUSION: IE is an uncommon infection in childhood and occurs primarily in patients with congenital heart disease. Rheumatic heart disease is rarely a predisposing cause in our local children. Early diagnosis of IE is challenging and depends on a high index of suspicion. Useful clues include the presence of splenomegaly, septic emboli, microscopic haematuria and high C-reactive protein level greater than 100mg/L. The Duke criteria for the diagnosis of IE are relevant locally, but if modified with an expanded list of minor criteria including the above useful clues, may increase the sensitivity of diagnosing definite IE. The presence of left-sided heart vegetations is a strong predictor of complications and must be treated aggressively.

Nucleic acid binding properties of thyminyl and adeninyl pyrrolidine-amide oligonucleotide mimics (POM).

Adeninyl POM was prepared using solid-phase peptide chemistry and shown to exhibit higher affinity for complementary DNA and RNA than the corresponding adeninyl PNA.

Design, synthesis, conformational analysis and nucleic acid hybridisation properties of thymidyl pyrrolidine-amide oligonucleotide mimics (POM).

Pyrrolidine-amide oligonucleotide mimics (POM) 1 were designed to be stereochemically and conformationally similar to natural nucleic acids, but with an oppositely charged, cationic backbone. Molecular modelling reveals that the lowest energy conformation of a thymidyl-POM monomer is similar to the conformation adopted by ribonucleosides. An efficient solution phase synthesis of the thymidyl POM oligomers has been developed, using both N-alkylation and acylation coupling strategies. 1H NMR spectroscopy confirmed that the highly water soluble thymidyl-dimer, T2-POM, preferentially adopts both a configuration about the pyrrolidine N-atom and an overall conformation in D2O that are very similar to a typical C3'-endo nucleotide in RNA. In addition the nucleic acid hybridisation properties of a thymidyl-pentamer, T5-POM, with an N-terminal phthalimide group were evaluated using both UV spectroscopy and surface plasmon resonance (SPR). It was found that T5-POM exhibits very high affinity for complementary ssDNA and RNA, similar to that of a T5-PNA oligomer. SPR experiments also showed that T5-POM binds with high sequence fidelity to ssDNA under near physiological conditions. In addition, it was found possible to attenuate the binding affinity of T5-POM to ssDNA and RNA by varying both the ionic strength and pH. However, the most striking feature exhibited by T5-POM is an unprecedented kinetic binding selectivity for ssRNA over DNA.

Effects of Eurycoma longifolia Jack on sexual qualities in middle aged male rats.

The effects of Eurycoma longifolia Jack were studied on the sexual qualities of middle aged male rats after dosing them with 0.5 g/kg of various fractions of E. longifolia whilst the control group received 3 ml/kg of normal saline daily for 12 weeks. Results showed than E. longifolia Jack enhanced the sexual qualities of the middle aged male rats by decreasing their hesitation time as compared to controls with various fractions of E. longifolia Jack produced 865-916 (91-96), 860-914 (92-98), 850-904 (93-99), 854-890 (95-99), 844-880 (94-98), 840-875 (94-98), 830-870 (94-98), 825-860 (94-98), 820-850 (96-99), 800-840 (93-98), 750-795 (94-99) and 650-754 sec (82-95%) in contrast to controls which produced 950 (100), 934 (100), 910 (100), 900 (100), 895 (100), 890 (100), 885 (100), 880 (100), 855 (100), 860 (100), 800 (100) and 790 sec (100%) throughout the investigation period. Besides these, there was a transient increase in the % of the male rats responding to the right choice after chronic administration of 0.5 g/kg E. longifolia Jack, with more than 50% of the male rats scored right choice after 2 weeks post-treatment and the effect was more prominent at the dose of the observation period. However, there was no sexual enhancement of the middle aged male rats which consumed normal saline since only 45-55% of the male rats responded to right choice throughout the investigation period. Hence, this study shows that E. longifolia Jack enhanced the sexual qualities of the middle aged male rats, further supports the folkuse of E. longifolia Jack as an aphrodisiac.