INTRODUCTION:: Infection with all serotypes of dengue virus (DV) results in augmented antigen presentation by MHC class I molecules. However, the upregulation of immunoproteasome subunits only results from infection with two serotypes. This study aims to elucidate changes in the expression of immunoproteasome subunits resulting from infection with DV, particularly DV serotype 2 (DV2).
METHODS:: HepG2 cells were grown in various culture milieu. Total cellular RNA and proteins were extracted and quantified.
RESULTS:: Results demonstrated sequestration of immunoproteasome subunits LMP2 and LMP7 in DV2-infected cells.
CONCLUSIONS:: This study provides insights into the mechanisms underlying immune evasion by DV.
MeSH terms: Dengue Virus/classification; Dengue Virus/metabolism*; Gene Expression Regulation; Humans; Protein Subunits; Proteasome Endopeptidase Complex/metabolism*; Hep G2 Cells; Serogroup
22q11.2 deletion syndrome (22q11.2 DS) is the most common microdeletion syndrome and is underdiagnosed in diverse populations. This syndrome has a variable phenotype and affects multiple systems, making early recognition imperative. In this study, individuals from diverse populations with 22q11.2 DS were evaluated clinically and by facial analysis technology. Clinical information from 106 individuals and images from 101 were collected from individuals with 22q11.2 DS from 11 countries; average age was 11.7 and 47% were male. Individuals were grouped into categories of African descent (African), Asian, and Latin American. We found that the phenotype of 22q11.2 DS varied across population groups. Only two findings, congenital heart disease and learning problems, were found in greater than 50% of participants. When comparing the clinical features of 22q11.2 DS in each population, the proportion of individuals within each clinical category was statistically different except for learning problems and ear anomalies (P
The cover image, by Paul Kruszka et al., is based on the Original Article 22q11.2 deletion syndrome in diverse populations, DOI: 10.1002/ajmg.a.38199. Individual images are property of the National Human Genome Research Institute and are in the public domain.
Drug permeation through the intercellular lipids, which pack around and between corneocytes, may be enhanced by increasing the thermodynamic activity of the active in a formulation. However, this may also result in unwanted drug crystallisation on and in the skin. In this work, we explore the combination of ATR-FTIR spectroscopy and multivariate data analysis to study drug crystallisation in the skin. Ex vivo permeation studies of saturated solutions of diclofenac sodium (DF Na) in two vehicles, propylene glycol (PG) and dimethyl sulphoxide (DMSO), were carried out in porcine ear skin. Tape stripping and ATR-FTIR spectroscopy were conducted simultaneously to collect spectral data as a function of skin depth. Multivariate data analysis was applied to visualise and categorise the spectral data in the region of interest (1700-1500cm(-1)) containing the carboxylate (COO(-)) asymmetric stretching vibrations of DF Na. Spectral data showed the redshifts of the COO(-) asymmetric stretching vibrations for DF Na in the solution compared with solid drug. Similar shifts were evident following application of saturated solutions of DF Na to porcine skin samples. Multivariate data analysis categorised the spectral data based on the spectral differences and drug crystallisation was found to be confined to the upper layers of the skin. This proof-of-concept study highlights the utility of ATR-FTIR spectroscopy in combination with multivariate data analysis as a simple and rapid approach in the investigation of drug deposition in the skin. The approach described here will be extended to the study of other actives for topical application to the skin.
A series of novel cholinesterase inhibitors containing nitrobenzoate core structure were synthesized by a facile and efficient method. The structure of the novel compounds were fully characterized and confirmed by analytical as well as spectroscopic methods. Compound indicated as 2f was found to possess the best cholinesterase inhibitory activities of all the evaluated compounds. Results suggest that 2f is a selective acetylcholinesterase inhibitor, although it also inhibits butyrylcholinesterase at higher concentration. Kinetics inhibition result suggest that 2f is a mixed-mode inhibitor of acetylcholinesterase. In addition, it was found to have low cytotoxicity. Molecular docking on compound 2f was carried out to rationalize the observed in vitro enzymatic assay results. Most importantly, the potential of nitrobenzoate derivatives as cholinesterase inhibitor was shown through this study. In summary, we discovered nitrobenzoates as a new scaffold that may eventually yield useful compounds in treatment of Alzheimer's disease.
Inflammatory bowel disease (IBD) is the main risk factor for developing colorectal cancer which is common in patients of all ages. 5-Aminosalicylic acid (5-ASA), structurally related to the salicylates, is highly active in the treatment of IBD with minor side effects. In this study, the synthesis of galactose and fructose esters of 5-ASA was planned to evaluate the role of glycoconjugation on the bioactivity of the parent drug. The antibacterial activity of the new compounds were evaluated against two Gram-negative and two Gram-positive species of bacteria, with a notable effect observed against Staphylococcus aureus and Escherichia coli in comparisons with the 5-ASA. Cytotoxicity testing over HT-29 and 3T3 cell lines indicated that the toxicity of the new products against normal cells was significantly reduced compared with the original drug, whereas their activity against cancerous cells was slightly decreased. The anti-inflammatory activity test in RAW264.7 macrophage cells indicated that the inhibition of nitric oxide by both of the monosaccharide conjugated derivatives was slightly improved in comparison with the non-conjugated drug.
Thiourea derivatives having benzimidazole 1-17 have been synthesized, characterized by 1H NMR, 13C NMR and EI-MS and evaluated for α-glucosidase inhibition. Identification of potential α-glucosidase inhibitors were done by in vitro screening of 17 thiourea bearing benzimidazole derivatives using Baker's yeast α-glucosidase enzyme. Compounds 1-17 exhibited a varying degree of α-glucosidase inhibitory activity with IC50 values between 35.83±0.66 and 297.99±1.20μM which are more better than the standard acarbose (IC50=774.5±1.94μM). Compound 10 and 14 showed significant inhibitory effects with IC50 value 50.57±0.81 and 35.83±0.66μM, respectively better than the rest of the series. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction of the compounds.
Current research is based on the synthesis of novel (E)-4-aryl-2-(2-(pyren-1-ylmethylene)hydrazinyl)thiazole derivatives (3-15) by adopting two steps route. First step was the condensation between the pyrene-1-carbaldehyde (1) with the thiosemicarbazide to afford pyrene-1-thiosemicarbazone intermediate (2). While in second step, cyclization between the intermediate (2) and phenacyl bromide derivatives or 2-bromo ethyl acetate was carried out. Synthetic derivatives were structurally characterized by spectroscopic techniques such as EI-MS, 1H NMR and 13C NMR. Stereochemistry of the iminic double bond was confirmed by NOESY analysis. All pure compounds 2-15 were subjected for in vitro β-glucuronidase inhibitory activity. All molecules were exhibited excellent inhibition in the range of IC50=3.10±0.10-40.10±0.90μM and found to be even more potent than the standard d-saccharic acid 1,4-lactone (IC50=48.38±1.05μM). Molecular docking studies were carried out to verify the structure-activity relationship. A good correlation was perceived between the docking study and biological evaluation of active compounds.
This review analyzes the economic costs of HF in Asia. The availability and quality of studies on the burden of osteoporosis in Asia are very scarce. There is a need to encourage more quality cost of osteoporosis studies based on standardized methods to convince healthcare authorities in implementing appropriate strategies.
INTRODUCTION: Osteoporosis fractures, especially hip fractures, impose large economic costs to governments and societies. This review aimed to systematically analyze available evidence on healthcare costs associated with osteoporosis-related hip fractures (HF) in Asia.
METHODS: Articles were systematically sought from databases including PubMed, EMBASE, and EBSCOHost between 2000 and 2015. Total costs associated with HF care, the cost components, and length of stays were retrieved and analyzed. Study designs were also qualitatively analyzed.
RESULTS: The availability of published studies on economic burden of HF in Asia is severely lacking with only 15 articles met the inclusion criteria. Even among the included studies, only two studies reported comprehensive costs evaluating all costs including indirect or intangible costs. Most studies satisfactorily reported criteria for conducting economic evaluation, but large variations existed in the methodological design. Due to study design and other influencing factors, large variation in the cost of HF treatment from US$774 to US$14,198.90 (median S$2943), representing an average of 18.95% (range: 3.58-57.05%) of the countries' 2014 GDP/capita, was observed. This highlighted the heavy burden of managing HF in Asia with about 40% of the included studies reported using more than one third of GDP/capita.
CONCLUSION: There is a paucity of burden of illness studies of osteoporosis in the Asian region. For the few available studies, there was a lack of standardization in methodological approach in evaluating the economic burden of the disease. There is a need to encourage more quality burden of illness studies of osteoporosis to inform policymakers in healthcare planning.
MeSH terms: Asia; Hip Fractures/economics*; Hip Fractures/therapy; Humans; Length of Stay/economics; Length of Stay/statistics & numerical data; Health Care Costs/statistics & numerical data*; Cost of Illness; Osteoporotic Fractures/economics*; Osteoporotic Fractures/therapy
Protein microarray is a miniaturized multi-analyte, solid-phased immunoassay where thousands of immobilized individual protein spots on a microscopic slide bind are bound to specific antibodies (immunoglobulins) from serum samples, which are then detected by fluorescent labeling. The image processing and pattern recognition are then quantitatively analyzed using advanced algorithms. Here, we describe the use of an in-house-produced complex protein microarray containing extracts and pure proteins that has been probed with antibodies present in the horse sera and detection by fluorophore-conjugated antibody and data analysis. The flexibility of the number and types of proteins that can be printed on the microarray allows different set of specific IgE immunoassay analysis to be carried out.
Isopods occur very commonly as parasites in food fishes. Parasitic isopods are typically marine and usually inhabit the warmer seas. They are blood-feeding; several species settle in the buccal cavity of fish, others live in the gill chamber or on the body surface including the fins. Isopods can cause morbidity and mortality in captive fish populations. The infestation usually pressure atrophy often accompanies the presence of larger parasites. The present study was aimed at collecting information on the neglected group of isopod parasites of the marine fishes from the Miri coastal environment, East Malaysia. A very little information available regarding the distribution of isopod parasites of Malaysian coastal environment. In the present study, nine isopod parasites were oberved from ten marine fish species. The maximum number of parasites were observed in the months of June and October, 2013. Maximum prevalence was observed in October (50 %) and the minimum was observed in June (7.14 %). The parasitic infestation may lead to an economic loss in commercial fish species.
The bopyrid isopods are common in wildMacrobrachiumspp. but not common in aquaculture condition. This is the first study that reports the parasitizing of bopyrid isopods on the culturedM. malcolmsonii. Bopyrid isopod (Probopyrus buitendijki) was identified in the branchial cavities of the fresh water prawn,M. malcolmsoniifrom grow-out culture pond at Kuriyamangalam, India.Macrobrachium malcolmsoniiis a new host forP. buitendijki. A total of 1323M. malcolmsoniiwere checked for this study. The overall prevalence of the parasitic infestation was reached 46.2 %. The parasitic infection was higher in female (83 %) than in male (3.4 %). Highest prevalence of infestation was found in the median size group (7-8 cm) (58.7 %). Infected females were not berried unlike uninfected prawns. The parasites cause infertility and does not found any organ deformities due to the infestation. The parasite was inversely attached in the gill chamber with no lesion on the gill but the infected branchial chamber became bulged.
The G antigen of Rh blood group system is present in almost all D-positive or C-positive red cells but absent from red cells lacking D and C antigens. The differentiation of anti-D and anti-C from anti-G is not necessary for routine transfusion; however, during pregnancy, it is important because anti-G can masquerade as anti-D and anti-C with initial antibody testing. The false presence of anti-D will exclude the patient from receiving anti-D immunoglobulin (RhIG) when the patient actually is a candidate for RhIG prophylaxis. Moreover, patients with positive anti-D or anti-G are at risk of developing hemolytic disease of the fetus and newborn and need close monitoring. Thus, proper identification allows the clinicians to manage patients properly. This case report highlights a rare case of anti-G together with anti-D and anti-C in a pregnant woman. This report disseminates knowledge on identification of anti-G and its importance in pregnant women.
The title diorganotin compound, [Sn(CH3)2(C28H32N2O4)], features a distorted SnC2NO2 coordination geometry almost inter-mediate between ideal trigonal-bipyramidal and square-pyramidal. The dianionic Schiff base ligand coordinates in a tridentate fashion via two alkoxide O and hydrazinyl N atoms; an intra-molecular hy-droxy-O-H⋯N(hydrazin-yl) hydrogen bond is noted. The alk-oxy chain has an all-trans conformation, and to the first approximation, the mol-ecule has local mirror symmetry relating the two Sn-bound methyl groups. Supra-molecular layers sustained by imine-C-H⋯O(hy-droxy), π-π [between dec-yloxy-substituted benzene rings with an inter-centroid separation of 3.7724 (13) Å], C-H⋯π(arene) and C-H⋯π(chelate ring) inter-actions are formed in the crystal; layers stack along the c axis with no directional inter-actions between them. The presence of C-H⋯π(chelate ring) inter-actions in the crystal is clearly evident from an analysis of the calculated Hirshfeld surface.
The complete mol-ecule of the title hydrazine carbodi-thio-ate complex, [Ni(C19H21N2S2)2], is generated by the application of a centre of inversion. The NiII atom is N,S-chelated by two hydrazinecarbodi-thio-ate ligands, which provide a trans-N2S2 donor set that defines a distorted square-planar geometry. The conformation of the five-membered chelate ring is an envelope with the NiII atom being the flap atom. In the crystal, p-tolyl-C-H⋯π(benzene- i Pr), i Pr-C-H⋯π(p-tol-yl) and π-π inter-actions [between p-tolyl rings with inter-centroid distance = 3.8051 (12) Å] help to consolidate the three-dimensional architecture. The analysis of the Hirshfeld surface confirms the importance of H-atom contacts in establishing the packing.
The title compound, [Cd2(C8H8NS2)4], is a centrosymmetric dimer with both chelating and μ2-tridentate di-thio-carbamate ligands. The resulting S5 donor set defines a Cd(II) coordination geometry inter-mediate between square-pyramidal and trigonal-bipyramidal, but tending towards the former. The packing features C-H⋯S and C-H⋯π inter-actions, which generate a three-dimensional network. The influence of these inter-actions, along with intra-dimer π-π inter-actions between chelate rings, has been investigated by an analysis of the Hirshfeld surface.
BACKGROUND: Bilateral sagittal split osteotomy (BSSO) is the most versatile procedure and adopted by many surgeons to relocate the mandible in patients having mandibular prognathism (MP). Injury to the inferior alveolar nerve (IAN) and unfavorable splits are two surgical complications of BSSO which are associated with mandibular morphology. Uses of cone beam computed tomography (CBCT) in providing 3-D images has gained a wider acceptance in surgical field nowadays. Its advantages are including reduced cost, lesser radiation dose and smaller physical footprint comparing to the conventional computed tomography.
PURPOSE: This study aims to identify the differences in morphology of prognathic and non-prognathic mandible at BSSO sites using cone beam computed tomography images.
METHODS: This retrospective study involved 51 CBCT images of patients having mandibular prognathism and without mandibular prognathism. The latter group made up from patients with Class I skeletal pattern. Samples were taken using purposive sampling method from two clinical centers.
RESULT: Prognathic mandible has higher lingula level, superiorly and buccally placed inferior alveolar nerve canal at distal second molar, thinner mediolateral width of ramus at anterior and posterior part and thinner anteroposterior width of the ramus.
CONCLUSION: Morphology of mandible in patients with mandibular prognathism (MP) was significantly different from patients without mandibular prognathism (WMP) for most of the parameters. The high risk parameters may be highlighted to the patients using cone beam computed tomography images.
BACKGROUND: Mortality associated with heart failure (HF) remains high. There are limited clinical data on mortality among HF patients from African populations. We examined the clinical characteristics, long-term outcomes, and prognostic factors of African HF patients with preserved, mid-range or reduced left ventricular ejection fraction (LVEF).
METHODS AND RESULTS: We conducted a retrospective longitudinal cohort study of individuals aged ≥18years discharged from first HF admission between January 1, 2009 and December 31, 2013 from the Cardiac Clinic, Directorate of Medicine of the Komfo Anokye Teaching Hospital, Ghana. A total of 1488 patients diagnosed of HF were included in the analysis. Of these, 345 patients (23.2%) had reduced LVEF (LVEF<40%) [HFrEF], 265(17.8%) with mid-range LVEF (40%≥LVEF<50%) [HFmEF] and 878 (59.0%) had preserved LVEF (LVEF≥50%) [HFpEF]. Kaplan-Meier curves and log-rank test demonstrated better prognosis for HFpEF compared to HFrEF and HFmEF patients. An adjusted Cox analysis showed a significantly lower risk of mortality for HFpEF (hazard ratio (HR); 0.74; 95% confidence interval (CI) 0.57-0.94) p=0.015). Multivariate analyses showed that age, higher New York Heart Association (NYHA) functional class, lower LVEF, chronic kidney disease, atrial fibrillation, anemia, diabetes mellitus and absence of statin and aldosterone antagonist treatment were independent predictors of mortality in HF. Although, prognostic factors varied across the three groups, age was a common predictor of mortality in HFpEF and HFmEF.
CONCLUSIONS: This study identified the clinical characteristics, long-term mortality and prognostic factors of African HF patients with reduced, mid-range and preserved ejection fractions in a clinical setting.
MeSH terms: Adult; Aged; Female; Follow-Up Studies; Ghana/epidemiology; Heart Failure/diagnosis*; Heart Failure/epidemiology*; Heart Failure/physiopathology; Hospitals; Humans; Longitudinal Studies; Male; Middle Aged; Outpatient Clinics, Hospital; Patient Admission/trends*; Prognosis; Retrospective Studies; Stroke Volume/physiology; Time Factors; Cohort Studies; Africa South of the Sahara/epidemiology
This study aimed to assess changes in oral cancer patients' health-related quality of life (HRQOL) and the impact of disease stage on HRQOL scores. HRQOL data were collected from seven hospital-based centres using the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) version 4.0 instrument. The independent samples t-test, χ(2) test, and paired samples t-test were used to analyse the data. A total of 300 patients were recruited. The most common oral cancer sub-site was tongue and floor of mouth (42.6%). Surgical intervention (41.1%) was the most common treatment modality. Significant differences in ethnicity and treatment modality were observed between early and late stage patients. Pre-treatment HRQOL scores were significantly lower for late than early stage patients. At 1 month post-treatment, the functional and head and neck domains and the FACT-H&N (TOI) summary scores showed significant deterioration in both early and late stage patients. In contrast, the emotional domain showed a significant improvement for early and late stage patients at 1, 3, and 6 months post-treatment. Although HRQOL deterioration was still observed among early and late stage patients at 6 months post-treatment, this was not statistically significant. In conclusion, advanced disease is associated with poorer HRQOL. Although ethnic differences were observed across different disease stages, the influence of ethnicity on patient HRQOL was not evident in this study.
MeSH terms: Head; Head and Neck Neoplasms; Humans; Mouth Floor; Mouth Neoplasms; Neck; Quality of Life