Drosophila modifier screens to identify novel neuropsychiatric drugs including aminergic agents for the possible treatment of Parkinson's disease and depression.

Small molecules that increase the presynaptic function of aminergic cells may provide neuroprotection in Parkinson's disease (PD) as well as treatments for attention deficit hyperactivity disorder (ADHD) and depression. Model genetic organisms such as Drosophila melanogaster may enhance the detection of new drugs via modifier or 'enhancer/suppressor' screens, but this technique has not been applied to processes relevant to psychiatry. To identify new aminergic drugs in vivo, we used a mutation in the Drosophila vesicular monoamine transporter (dVMAT) as a sensitized genetic background and performed a suppressor screen. We fed dVMAT mutant larvae ∼ 1000 known drugs and quantitated rescue (suppression) of an amine-dependent locomotor deficit in the larva. To determine which drugs might specifically potentiate neurotransmitter release, we performed an additional secondary screen for drugs that require presynaptic amine storage to rescue larval locomotion. Using additional larval locomotion and adult fertility assays, we validated that at least one compound previously used clinically as an antineoplastic agent potentiates the presynaptic function of aminergic circuits. We suggest that structurally similar agents might be used to development treatments for PD, depression and ADHD, and that modifier screens in Drosophila provide a new strategy to screen for neuropsychiatric drugs. More generally, our findings demonstrate the power of physiologically based screens for identifying bioactive agents for select neurotransmitter systems

Efficiency enhancement and angle-dependent color change in see-through organic photovoltaics using distributed Bragg reflectors

A distributed Bragg reflector (DBR) is conducted as a bottom reflector in see-through organic photovoltaics (OPVs) with an active layer of poly(3-hexylthiophene) and phenyl-C61-butyric acid methyl ester (P3HT:PCBM). The DBR consists of alternative layers of the high-and low-refractive index materials of Ta2O5 (n = 2.16) and SiO2 (n = 1.46). The DBR selectively reflects the light within a specific wavelength region (490 nm-630 nm) where the absorbance of P3HT: PCBM is maximum. The see-through OPVs fabricated on DBR exhibit efficiency enhancement by 31% compared to the device without DBR. Additionally, the angle-dependent transmittance of DBR is analysed using optical simulation and verified by experimental results. As the incident angle of light increases, peak of reflectance shifts to shorter wavelength and the bandwidth gets narrower. This unique angle-dependent optical properties of DBR allows the facile color change of see-through OPVs. (C) 2016 AIP Publishing LLC.open1110sciescopu

Burden of postinfectious symptoms after acute Dengue, Vietnam.

We assessed predominantly pediatric patients in Vietnam with dengue and other febrile illness 3 months after acute illness. Among dengue patients, 47% reported >1 postacute symptom. Most resolved by 3 months, but alopecia and vision problems often persisted. Our findings provide additional evidence on postacute dengue burden and confirm children are affected

Exploration of an innovative draw solution for a forward osmosis-membrane distillation desalination process

© 2017, Springer-Verlag Berlin Heidelberg. Forward osmosis (FO) has emerged as a viable technology to alleviate the global water crisis. The greatest challenge facing the application of FO technology is the lack of an ideal draw solution with high water flux and low reverse salt flux. Hence, the objective of this study was to enhance FO by lowering reverse salt flux and maintaining high water flux; the method involved adding small concentrations of Al2(SO4)3 to a MgCl2 draw solution. Results showed that 0.5 M MgCl2 mixed with 0.05 M of Al2(SO4)3 at pH 6.5 achieved a lower reverse salt flux (0.53 gMH) than that of pure MgCl2 (1.55 gMH) using an FO cellulose triacetate nonwoven (CTA-NW) membrane. This was due possibly to the flocculation of aluminum hydroxide in the mixed draw solution that constricted membrane pores, resulting in reduced salt diffusion. Moreover, average water fluxes of 4.09 and 1.74 L/m2-h (LMH) were achieved over 180 min, respectively, when brackish water (5 g/L) and sea water (35 g/L) were used as feed solutions. Furthermore, three types of membrane distillation (MD) membranes were selected for draw solution recovery; of these, a polytetrafluoroethylene membrane with a pore size of 0.45 μm proved to be the most effective in achieving a high salt rejection (99.90%) and high water flux (5.41 LMH) in a diluted draw solution

Endothelial nitric oxide pathways in the pathophysiology of dengue: a prospective observational study.

Background: Dengue can cause increased vascular permeability that may lead to hypovolemic shock. Endothelial dysfunction may underlie this; however the association of endothelial nitric oxide pathways with disease severity is unknown. Methods: We performed a prospective observational study in two Vietnamese hospitals, assessing patients presenting early (<72 hours fever) and patients hospitalized with warning signs or severe dengue. The reactive hyperaemic index (RHI), which measures endothelium-dependent vasodilation and is a surrogate marker of endothelial function and NO bioavailability was evaluated using peripheral artery tonometry (EndoPAT) and plasma levels of L-arginine, Arginase-1 and ADMA were measured at serial time-points. The main outcome of interest was plasma leakage severity. Results: 314 patients were enrolled, median age of the participants was 21 (IQR 13-30) years. No difference was found in the endothelial parameters between dengue and other febrile illness (OFI). Considering dengue patients, the RHI was significantly lower for patients with severe plasma leakage compared to those with no leakage (1.46 vs. 2.00, P<0.001), over acute time-points, apparent already in the early febrile phase (1.29 vs. 1.75, P=0.012). RHI correlated negatively with arginase-1, and positively with L-arginine (P=0.001). Endothelial dysfunction/NO bioavailability is associated with worse plasma leakage, occurs early in dengue illness and correlates with hypoargininaemia and high arginase-1 levels

First detection of a Vssc allele V1016G conferring a high level of insecticide resistance in Aedes albopictus collected from Europe (Italy) and Asia (Vietnam), 2016. A new emerging threat to controlling arboviral diseases

Introduction Aedes albopictus (Skuse) is an important vector of arboviral diseases, including dengue, chikungunya and Zika virus disease. Monitoring insecticide resistance and mechanisms by which the mosquito develops resistance is crucial to minimise disease transmission. Aim To determine insecticide resistance status and mechanisms in Ae. albopictus from different geographical regions. Methods We sampled 33 populations of Ae. albopictus from Asia, Europe and South America, and tested these for susceptibility to permethrin, a pyrethroid insecticide. In resistant populations, the target site for pyrethroids, a voltage-sensitive sodium channel (Vssc) was genotyped. Three resistant sub-strains, each harbouring a resistance allele homozygously, were established and susceptibilities to three different pyrethroids (with and without a cytochrome P450 inhibitor) were assayed. Results Most populations of Ae. albopictus tested were highly susceptible to permethrin but a few from Italy and Vietnam (4/33), exhibited high-level resistance. Genotyping studies detected a knockdown resistance (kdr) allele V1016G in Vssc for the first time in Ae. albopictus. Two previously reported kdr alleles, F1534C and F1534S, were also detected. The bioassays indicated that the strain homozygous for the V1016G allele showed much greater levels of pyrethroid resistance than other strains harbouring F1534C or F1534S. Conclusion The V1016G allele was detected in bothAsian and Italian Ae. albopictus populations, thus a spread of this allele beyond Italy in Europe cannot be ruled out. This study emphasises the necessity to frequently and regularly monitor the V1016G allele in Ae. albopictus, particularly where this mosquito species is the main vector of arboviruses

Influenza A H5N1 and HIV co-infection: case report

<p>Abstract</p> <p>Background</p> <p>The role of adaptive immunity in severe influenza is poorly understood. The occurrence of influenza A/H5N1 in a patient with HIV provided a rare opportunity to investigate this.</p> <p>Case Presentation</p> <p>A 30-year-old male was admitted on day 4 of influenza-like-illness with tachycardia, tachypnea, hypoxemia and bilateral pulmonary infiltrates. Influenza A/H5N1 and HIV tests were positive and the patient was treated with Oseltamivir and broad-spectrum antibiotics. Initially his condition improved coinciding with virus clearance by day 6. He clinically deteriorated as of day 10 with fever recrudescence and increasing neutrophil counts and died on day 16. His admission CD4 count was 100/μl and decreased until virus was cleared. CD8 T cells shifted to a CD27⁺CD28^-phenotype. Plasma chemokine and cytokine levels were similar to those found previously in fatal H5N1.</p> <p>Conclusions</p> <p>The course of H5N1 infection was not notably different from other cases. Virus was cleared despite profound CD4 T cell depletion and aberrant CD8 T cell activation but this may have increased susceptibility to a fatal secondary infection.</p

The internal thoracic artery skeletonization study: A paired, within-patient comparison [NCT00265499]

BACKGROUND: Traditional harvesting of the internal thoracic artery (ITA) for use as a conduit in coronary bypass surgery involves the dissection of a rim of tissue surrounding the artery on either side. Recent studies, primarily observational, have suggested that skeletonization of the ITA can improve conduit flow, increase length, and reduce the risk of deep sternal infection in high risk patients. Furthermore, skeletonization of the ITA can potentially preserve intercostal nerves and reduce post-operative pain and dysesthesias associated with ITA harvesting. In order to assess the effects of ITA skeletonization, we report a prospective, randomized, within-patient study design that shares many features of a cross-over study. METHODS: Patients undergoing bilateral internal thoracic artery harvest will be randomized to having one side skeletonized and the other harvested in a non-skeletonized manner. Outcome measures include ITA flow and length measured intra-operatively, post-operative pain and dysesthesia, evaluated at discharge, four weeks, and three months post-operatively, and sternal perfusion assessed using single photon emission computed tomography. Harvest times as well as safety endpoints of ITA injury will be recorded. DISCUSSION: This study design, using within-patient comparisons and paired analyses, minimizes the variability of the outcome measures, which is seldom possible in the evaluation of surgical techniques, with minimal chance of carryover effects that can hamper the interpretation of traditional cross-over studies. This study will provide a valid evaluation of clinically relevant effects of internal thoracic artery skeletonization in improving outcomes following coronary artery bypass surgery