Engineered NS1 for Sensitive,Specific Zika Virus Diagnosis from Patient Serology

Dengue virus (DENV) and Zika virus (ZIKV) belong to the Flaviviridae family of viruses spread by Aedes aegypti mosquitoes in tropical and subtropical areas. Accurate diagnostic tests to differentiate the 2 infections are necessary for patient management and disease control. Using characterized ZIKV and DENV patient plasma in a blind manner, we validated an ELISA and a rapid immunochromatographic test for ZIKV detection. We engineered the ZIKV nonstructural protein 1 (NS1) for sensitive serologic detection with low cross reactivity against dengue and developed monoclonal antibodies specific for the ZIKV NS1 antigen. As expected, the serologic assays performed better with convalescent than acute plasma samples; the sensitivity ranged from 71% to 88%, depending on the performance of individual tests (IgM/IgG/NS1). Although serologic tests were generally less sensitive with acute samples, our ZIKV NS1 antibodies were able to complement the serologic tests to achieve greater sensitivity for detecting early infections.     

Effectiveness of an acellular pertussis vaccine in Japanese children during a non-epidemic period: a matched case-control study

The number of pertussis cases in Japan has decreased dramatically following the nationwide use of an acellular pertussis vaccine combined with diphtheria-tetanus toxoids (DTaP vaccines) which began in 1981. However, the effectiveness of the DTaP vaccine has not been systematically evaluated using appropriate epidemiological methods during a non-epidemic period in Japan. We evaluated the vaccine effectiveness (VE) of the Kaketsuken DTaP vaccine which contains two-component pertussis antigens in Japanese children from 1999 to 2001 using a matched case-control design and data from the Basic Resident Registration and Maternal and Child Health Handbooks. The DTaP vaccination history of 15 children with pertussis and 59 controls was obtained. The VE of 3 or 4 pertussis vaccinations compared with non-vaccination (baseline) was 96.9% for coughing attacks that lasted 7 days, 96.4% for those lasting 14 days, and 95.9% for those lasting 21 days. These findings suggest that DTaP vaccination effectively prevented pertussis during a non-epidemic period in Japan.     

Proof of concept pilot study: prevalence of grass virus infection and the potential for effects on the allergenic potency of pollen

Background

Wild plants harbour a variety of viruses and these have the potential to alter the composition of pollen. The potential consequences of virus infection of grasses on pollen-induced allergic disease are not known.

Methods

We have collected pollen from Dactylis glomerata (cocksfoot; a grass species implicated as a trigger of allergic rhino-conjunctivitis) from Wytham Wood, Oxfordshire UK. Extracts were prepared from pollen from uninfected grass, and from grass naturally infected by the Cocksfoot streak potyvirus (CSV). Preparations of pollen from virus-infected and non-infected grasses were employed in skin testing 15 grass pollen-allergic subjects with hayfever. Allergen profiles of extracts were investigated by Western blotting for IgE with sera from allergic subjects.

Results

The prevalence of CSV infection in cocksfoot grasses sampled from the study site varied significantly over an eight-year period, but infection rates of up to 70% were detected. Virus infection was associated with small alterations in the quantities of pollen proteins detected by polyacrylamide gel electrophoresis, and in the patterns of allergens identified by Western blotting with IgE from grass pollen allergic subjects. For individual subjects there were differences in potencies of standardised extracts of pollen from virus-free and virus-infected plants as assessed by skin testing, though a consistent pattern was not established for the group of 15 subjects.

Conclusion

Infection rates for CSV in cocksfoot grass can be high, though variable. Virus-induced alterations in components of grass pollen have the potential to alter the allergenic potency.

     

Simple Nutrition Screening Tool for Pediatric Inpatients

Background: Pediatric nutrition risk screening tools are not routinely implemented throughout many hospitals, despite prevalence studies demonstrating malnutrition is common in hospitalized children. Existing tools lack the simplicity of those used to assess nutrition risk in the adult population. This study reports the accuracy of a new, quick, and simple pediatric nutrition screening tool (PNST) designed to be used for pediatric inpatients. Materials and Methods: The pediatric Subjective Global Nutrition Assessment (SGNA) and anthropometric measures were used to develop and assess the validity of 4 simple nutrition screening questions comprising the PNST. Participants were pediatric inpatients in 2 tertiary pediatric hospitals and 1 regional hospital. Results: Two affirmative answers to the PNST questions were found to maximize the specificity and sensitivity to the pediatric SGNA and body mass index (BMI) z scores for malnutrition in 295 patients. The PNST identified 37.6% of patients as being at nutrition risk, whereas the pediatric SGNA identified 34.2%. The sensitivity and specificity of the PNST compared with the pediatric SGNA were 77.8% and 82.1%, respectively. The sensitivity of the PNST at detecting patients with a BMI z score of less than ?2 was 89.3%, and the specificity was 66.2%. Both the PNST and pediatric SGNA were relatively poor at detecting patients who were stunted or overweight, with the sensitivity and specificity being less than 69%. Conclusion: The PNST provides a sensitive, valid, and simpler alternative to existing pediatric nutrition screening tools such as Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP), Screening Tool Risk on Nutritional status and Growth (STRONGkids), and Paediatric Yorkhill Malnutrition Score (PYMS) to ensure the early detection of hospitalized children at nutrition risk.     

Subacute inhalation toxicity assessment of fly ash from industrial waste incinerators

Fly ash from industrial waste incinerators has been a significant concern because of their constituent toxic heavy metals and organic compounds. The objective of this study was to identify the subacute inhalation toxicity of fly ash from industrial waste incinerators, using whole body inhalation exposure chambers. Male and female groups of Sprague-Dawley rats were exposed to fly ash by inhalation of concentrations of 0, 50, 100, 200?mg/m(3), for 6?h/day, 5 days/week for 4 weeks. There was no significant difference in body weight, and relative organ weight to body weight, between the exposure groups and the control group. Hematological examinations revealed a significant increase of monocyte counts in fly ash exposed rats and brown pigment laden macrophage was found in the lungs of rats exposed to high concentration of fly ash. A decrease of blood glucose levels and an increase in glutamate oxaloacetate transaminase activity were observed in fly ash treated rats. There was also a significant increase of lactate dehydrogenase levels in rat blood exposed fly ash. A significant dose-dependent increase of DNA damage was found in lymphocytes, spleen, bronchoalveolar lavage, liver, lung, and thymus of rats exposed to fly ash. In addition, the level of lipid peroxidation was increased in the plasma of rats exposed to a high concentration of fly ash. These results suggest that inhalation of fly ash from industrial waste incinerators can induce histopathologic, hematological, and serum biochemical changes and oxidative damage.     

Evaluation of Senegalese plants used in malaria treatment: focus on Chrozophora senegalensis

An ethnobotanical study was conducted in the Dakar area of Senegal to investigate the species used in the treatment of malaria. Seven plants are principally used: Cissampelos mucronata, Maytenus senegalensis, Terminalia macroptera, Bidens engleri, Ceratotheca sesamoides, Chrozophora senegalensis and Mitracarpus scaber. From a bibliographic study, it had been shown that the Cissampelos mucronata, Maytenus senegalensis and Terminalia macroptera have already been studied by several authors, and so only Bidens engleri, Ceratotheca sesamoides, Chrozophora senegalensis and Mitracarpus scaber were evaluated in the present study. For each plant, extracts were prepared with different solvents and tested in vitro on two chloroquine-resistant Plasmodium falciparum strains. Crude extracts from the leaves and the stems of Chrozophora senegalensis showed the best in vitro results. The IC(50) value of an aqueous extract of Chrozophora senegalensis was 1.6 microg/ml without cytotoxicity. The in vivo antiplasmodial activity of Chrozophora extracts was determined by both the oral and the intraperitoneal ways. The stages of Plasmodium cycle targeted by Chrozophora were then studied in vitro. These results could justify the traditional use of this plant in malaria treatment.     

消旋15(R)-15-甲基PGE2甲酯的合成

d,l-15(R)-15-Methyl-PGF_2α methyl ester 11-trimethylsilyl ether(II)wasprepared from selective monosilylation of d,l-15(R)-15-methyl-PGF_2αmethyl ester(I) withtrimethylsilyldiethylamine in acetone. Oxidation of(II ) with Collin's reagent gave d,l-15(R)-15-methyl-PGE₂ methyl ester 11-trimethylsilyl ether(III)which,without purification,was converted to d,l-15(R)-15-methyl-PGE₂ methyl ester(IV)under mild acidic conditions.     

Additive effect of unoprostone and latanoprost in patients with elevated intraocular pressure.

AIMS: To assess the additive effect of unoprostone and latanoprost in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT) METHODS: 32 patients with POAG or OHT were randomised to receive either latanoprost once daily or unoprostone twice daily for 4 weeks. After 4 weeks, all patients received both latanoprost and unoprostone for another 4 weeks. The IOP was measured at 9 am and 5 pm on the baseline, day 28, and day 56 visits, and at 9 am on day 14 and day 42 visits. The medications were given to the patients in an open label fashion. The observer was masked to the treatment given. The mean of the measurements was calculated. Safety parameters were also recorded. The additive effect of the medications was assessed by the reduction in intraocular pressure (IOP) when both medications were used, compared with when one medication was used. RESULTS: 28 patients completed both treatment periods and had IOP data available for evaluation. After 1 month of treatment, latanoprost significantly reduced IOP (mean by 6.1 (SEM 0.8) mm Hg (p<0.001) and unoprostone by 4.9 (1.0) mm Hg (p<0.001) from the baseline of 24.4 (0.6) mm Hg and 24.4 (1.1) mm Hg respectively (p = 0.18). When latanoprost once daily was given to patients treated with unoprostone, there was additional IOP lowering of 1.9 (0.6) mm Hg (p = 0.012). However, adding unoprostone to those being treated with latanoprost produced an IOP change of +0.4 (0.5) mm Hg (p = 0.42). Ocular symptoms and findings were mild and equally distributed between treatment groups, and after combined therapy. Hyperaemia and ocular irritation were the most frequently reported events. Over a third of patients experienced ocular irritation with the combination of medications. CONCLUSIONS: Latanoprost once daily causes additional IOP lowering in eyes which were being treated with unoprostone twice a day. However, there was no additional IOP lowering when unoprostone was added to eyes which were being treated with latanoprost. Both drugs were well tolerated together with few ocular adverse events.     

Optical coherence tomography of choroidal neovascularization in high myopia

AIM: To investigate morphologic changes in the eye with choroidal neovascularization (CNV) in high myopia using optical coherence tomography (OCT). METHODS: Optical coherence tomography was performed in 35 patients (42 eyes) with myopic CNV. Myopic CNV was divided into active, scar, or atrophic stages based on funduscopic and fluorescein angiographic findings. The characteristics of OCT findings in each stage were identified. RESULTS: In the active stage (11 eyes), OCT clearly displayed a neovascular membrane as a highly reflective dome-like elevation above the retinal pigment epithelium (RPE). No apparent subretinal fluid accumulation around the CNV was identified. In the scar stage (12 eyes), only the surface of the CNV showed high reflectivity, which was markedly attenuated below the surface. In the atrophic stage (19 eyes), the CNV had become totally flat and chorioretinal atrophy around the regressed CNV showed high reflectivity. CONCLUSIONS: Optical coherence tomography demonstrated characteristic features at each stage of myopic CNV. Optical coherence tomography appears to be useful in evaluating the stage and activity of myopic CNV.