Advances in the management of diabetic macular oedema based on evidence from the Diabetic Retinopathy Clinical Research Network

The Diabetic Retinopathy Clinical Research Network (DRCR.net) performs studies on new treatments for diabetic retinopathy. This review aims to summarise recent findings from DRCR.net studies on the treatment of diabetic macular oedema. We performed a PubMed search of articles from the DRCR.net, which included all studies pertaining to the treatment of diabetic maculopathy. The main outcome measures were retinal thickening as assessed by central subfield thickness on optical coherence tomography and improvement of visual acuity on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Findings from each study were divided into modalities of treatment, namely photocoagulation, bevacizumab, triamcinolone, ranibizumab and vitrectomy. While modified ETDRS focal/grid laser remains the standard of care, intravitreal corticosteroids or anti-vascular endothelial growth factor agents have also proven to be effective, although they come with associated side effects. The choice of treatment modality for diabetic macular oedema is a clinical judgement call, and depends on the patient’s clinical history and assessment.     

The valine allele of the V89L polymorphism in the 5-alpha-reductase gene confers a reduced risk for hypospadias

CONTEXT: Hypospadias is one of the most common malformations in man, with an incidence of 1:300 in newborn boys. No gene has been identified that causes isolated hypospadias, but the androgenic influence is important during male genital development. OBJECTIVE: A key enzyme for the androgenic function is steroid 5-alpha-reductase (SRD5A2). The V89L polymorphism in the SRD5A2 gene has been studied and found to be of functional importance. The leucine version of the enzyme is 30% less efficient than the valine variant. DESIGN, SETTING, PATIENTS, AND RESULTS: We have genotyped 158 hypospadias cases and 96 unaffected controls for this polymorphism and found a significant negative association for the V89 allele in hypospadias (odds ratio, 0.24; 95% confidence interval, 0.14-0.41 for homozygous individuals). This indicates that a fully functional 5-alpha-reductase enzyme (homozygous for V89) protects the male urethral development. This association is shown regardless of heredity, ethnicity, and severity of phenotype. We have also sequenced a selected material of 37 sporadic cases of more severe hypospadias for mutations in the androgen receptor AR, SRD5A2, and 17beta-hydroxysteroid dehydrogenase HSD17B3 genes and found only two previously described mutations, one in the AR and one in the SRD5A2 gene. CONCLUSION: This finding is in accordance with the assumption that functional polymorphisms may play an important role in complex disorders such as hypospadias when several genes as well as environmental factors contribute to the etiology.     

Ten-year survival and factors associated with increased mortality in patients admitted for acute decompensated heart failure in Thailand

INTRODUCTIONData on the long-term outcomes of Asian patients admitted for acute decompensated heart failure is scarce. The objectives of this study were to determine short-term, intermediate-term and long-term survival among patients admitted for acute decompensated heart failure in Thailand, and to identify factors independently associated with increased mortality.METHODSPatients who were admitted with a primary diagnosis of heart failure were enrolled in the Thai Acute Decompensated Heart Failure Registry (ADHERE) from 18 hospitals located across Thailand during 2006. Medical record data was collected according to ADHERE protocol. Mortality data was collected from death certificates on file at the Thailand Bureau of Registration Administration.RESULTSA total of 1,451 patients were included. The mean age of the patients was 63.7 ± 14.4 years, and 49.7% were male. One-year, five-year and ten-year mortality rates in Thai patients admitted for acute decompensated heart failure were 28.0%, 58.2% and 73.3%, respectively. Independent predictors of increased mortality were identified. There were more cardiovascular-related deaths than non-cardiovascular-related deaths (54.6% vs. 45.4%, respectively).CONCLUSIONSThe ten-year mortality rate in Thai patients admitted for acute decompensated heart failure was 73.3%. Many factors were found to be independently associated with increased mortality, including left ventricular ejection fraction.     

An efficient multicomponent synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a magnetic nanoparticle supported Lewis acidic deep eutectic solvent

A mild and highly efficient reaction for the synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a magnetically supported Lewis acidic deep eutectic solvent on magnetic nanoparticles (LADES@MNP) has been developed via one-pot multicomponent processes under solvent-free sonication. These reactions have good to excellent yields, mild conditions, and work-up simplicity. This method represents a new method for the preparation of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles. More importantly, LADES@MNP can be easily recovered by magnetic separation and reused five times without significant loss of catalytic activity.

A mild and highly efficient method for the synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a Lewis acidic deep eutectic solvent on magnetic nanoparticles (LADES@MNP).     

Implant-guided volumetric analysis of edentulous maxillary bone with cone-beam computerized tomography scan. Maxillary sinus pneumatization classification

The primary goal of this anatomic study was to measure the average bone volume of the edentulous maxilla with a cone-beam computerized tomography (CBCT) scan and to determine its suitability for implant treatment without additional bone grafting. The secondary goal of the study was to estimate the degree of sinus pneumatization (SP) in reviewed CBCT scans, assess the sinus-to-maxillary bone interrelationship in edentulism, and attempt to classify maxillary sinuses based on the degree of their pneumatization. This retrospective radiographic quantitative study consisted of the analysis of CBCT scans of 30 randomly selected maxillary edentulous patients who presented in 2008-2010 to the University of the Pacific, Arthur A. Dugoni School of Dentistry, for evaluation and treatment of their edentulism. A volume of edentulous maxillary bone mesial to the maxillary sinuses (intersinal region) that can be used for a full-arch implant treatment was evaluated based on specifically selected and clinically relevant measurement criteria. There were 30 CBCT scans of maxillary edentulous patients reviewed (9 men, 21 women) with a mean age of 67.3 years (range, 41 to 92 years). The total mean maxillary bone volume (MMBV) suitable for implantation was 4?408.1 mm(3) and ranged from 1489.7 to 7263.1 mm(3). The MMBV in the study was higher than an assumed or hypothetical bone volume minimally suitable for 4-implant treatment as proposed by the authors for comparative purposes (3500 mm(3)). The degree of SP as seen on a CBCT scan (60 sinuses analyzed on panoramic images of 30 CBCT scans) had the following results in the study: SP0 (clear: not interfering with implant treatment in cases of high/small sinus), 2 sinuses or 3.3%; SP1 (mild sinus enlargement), 29 sinuses or 48.3%; SP2 (moderate SP), 16 sinuses or 26.7%; SP3 (severe SP), 9 sinuses or 15.0%; and SP4 (extreme), 4 sinuses or 6.7%. Most analyzed maxillary sinuses (47 of 60, or 78.3%) were in the clear, mild, or moderate categories of SP (SP0, SP1, and SP2), which have a sufficient amount of maxillary bone beneath the maxillary sinuses to allow a full-arch implant treatment. An inverse correlation between SP and MMBV was observed. Although many other clinical criteria are important (bone quality, alveolar crest anatomy, etc), the results of this CBCT radiographic study indicate that in many maxillary edentulous cases, the existing bone quantity (volume) can be sufficient for a full-arch maxillary implant treatment with at least 4 implants without the additional trauma or expense of bone grafts and sinus lifts. A variety of implant treatment options can be proposed based on maxillary bone availability and bone-to-sinus interrelationship. It appears that with age and edentulism, the amount of available maxillary bone is steadily decreasing.     

Presentation of antigen in immune complexes is boosted by soluble bacterial immunoglobulin binding proteins

Using a snake toxin as a proteic antigen (Ag), two murine toxin-specific monoclonal antibodies (mAbs), splenocytes, and two murine Ag-specific T cell hybridomas, we showed that soluble protein A (SpA) from Staphylococcus aureus and protein G from Streptococcus subspecies, two Ig binding proteins (IBPs), not only abolish the capacity of the mAbs to decrease Ag presentation but also increase Ag presentation 20-100-fold. Five lines of evidence suggest that this phenomenon results from binding of an IBP-Ab-Ag complex to B cells possessing IBP receptors. First, we showed that SpA is likely to boost presentation of a free mAb, suggesting that the IBP-boosted presentation of an Ag in an immune complex results from the binding of IBP to the mAb. Second, FACS analyses showed that an Ag-Ab complex is preferentially targeted by SpA to a subpopulation of splenocytes mainly composed of B cells. Third, SpA-dependent boosted presentation of an Ag-Ab complex is further enhanced when splenocytes are enriched in cells containing SpA receptors. Fourth, the boosting effect largely diminishes when splenocytes are depleted of cells containing SpA receptors. Fifth, the boosting effect occurs only when IBP simultaneously contains a Fab and an Fc binding site. Altogether, our data suggest that soluble IBPs can bridge immune complexes to APCs containing IBP receptors, raising the possibility that during an infection process by bacteria secreting these IBPs, Ag-specific T cells may activate IBP receptor-containing B cells by a mechanism of intermolecular help, thus leading to a nonspecific immune response.     

Development of a portable electrochemical loop mediated isothermal amplification (LAMP) device for detection of hepatitis B virus

The objective of this study was to develop a simple, inexpensive prototype device for rapid detection of hepatitis B virus (HBV). The device was able to simultaneously amplify, detect and quantify the target HBV DNA. The system was fabricated from a custom-made electrochemical set-up of which the temperature was thermostatically controlled by a water bath. Real-time monitoring of HBV DNA was accomplished by measuring the response of redox indicator in the reaction mixture. Concentration of HBV DNA in the samples was determined from the peak high ratio (PHR) and threshold time relationship. The signal was processed by sigmoidal model fitting to enhance the accuracy of the results. Key parameters including concentrations of redox indicator and reaction temperatures were optimized. Sensitivity and specificity of the method toward HBV DNA were evaluated. The prototype was capable of real-time amplification and detection of HBV DNA with concentration as low as 6.18 fg μl⁻¹. The test showed high specificity against HBV DNA. The system was also able to detect HBV positive serum directly with simple thermal pretreatment instead of tedious DNA extraction. The electrochemical set-up was compatible with microfluidic platforms and can be readily adapted for efficient and high throughput point-of-care (POC) diagnosis of HBV.

A novel prototype device using LAMP and electrochemical drop cell set-up for rapid detection of hepatitis B virus.     

Efficient nickel or copper oxides decorated graphene–polyaniline interface for application in selective methanol sensing

Graphene sheets decorated with nickel or copper oxides that were anchored on polyaniline (denoted as PANI-graphene/NiO and PANI-graphene/CuO) were prepared by a simple, easy to-control electrochemical method and applied as novel materials for sensitive and selective methanol sensing. The fabricated sensors exhibited good electrocatalytic activity, appropriate dynamic linear range (20–1300 mM), sensitivity (0.2–1.5 μA mM⁻¹ cm⁻²) and excellent selectivity towards methanol. It should be highlighted from the selectivity tests that no significant interference was observed from ethanol and other alcohols. To our best knowledge, using inexpensive but efficient transition metals like Ni, Cu instead of Pt, Pd and their composites with PANI, graphene would be scientifically novel and practically feasible approach for sensor fabrication that could be potentially used to identify methanol adulteration in counterfeit alcoholic beverages.

PANI/graphene/NiO or PANI/graphene/CuO were prepared by a simple, easy to-control electrochemical method and applied as novel materials for sensitive and selective methanol sensing.