Tolerability and efficacy of single dose albendazole, diethylcarbamazine citrate (DEC) or co-administration of albendazole with DEC in the clearance of Wuchereria bancrofti in asymptomatic microfilaraemic volunteers in Pondicherry, South India: a hospital-based study

BACKGROUND: The tolerability and efficacy of single dose albendazole (400 mg), diethylcarbamazine citrate (DEC) (6 mg/kg bodyweight) or co-administration of albendazole (400 mg) + DEC (6 mg/kg bodyweight) was studied in 54 asymptomatic Wuchereria bancrofti microfilaraemic volunteers in a double blind hospital-based clinical study. RESULTS: There was no significant difference in the overall incidence of adverse reactions between the three drug groups [42.1% (albendazole), 52.9% (DEC) and 61.1% (albendazole + DEC); P > 0.05]. The mean score of adverse reaction intensity did not differ significantly between the DEC and albendazole + DEC groups. However, the values in these two groups were significantly higher compared to that of albendazole alone [1.8 ± 3.0 (albendazole) vs. 5.6 ± 7.1 (DEC), 6.7 ± 6.6 (albendazole + DEC); P < 0.05]. By day 360 post-therapy there was no significant difference between the three drug groups in relation to the clearance of microfilaria [26.3% (albendazole), 17.6% (DEC), 27.8% (albendazole + DEC)], reduction in geometric mean parasite density [94.7% (albendazole), 89.5% (DEC), 95.4% (albendazole + DEC)] or reduction in filarial antigenaemia [83% (albendazole), 87% (DEC), 75% (albendazole + DEC)]. Furthermore, there was a significant decrease in mean geometric parasite density (P < 0.05) as well as antigenaemia optical density values (P < 0.01) between pre-therapy levels and day 360 post-therapy in all three groups. CONCLUSIONS: This study has shown that single dose albendazole (400 mg) has similar efficacy in the clearance of microfilaria as that of DEC or the co-administration of the two drugs. The results strengthen the rationale of using albendazole for mass annual single dose administration for the control of transmission of lymphatic filariasis

Relationship between morphological and amplified fragment length polymorphism (AFLP) marker based genetic distance with heterosis in hot pepper (Capsicum annuum L.)

Identification of potential parents that produce the hybrids with superior yield is the most important step in developing hybrids to save the substantial resources. The present study was carried out to assess the morphological and amplified fragment length polymorphism (AFLP) marker based genetic diversity, to estimate mid parent heterosis and to correlate the estimated parental genetic diversity with heterosis chilli. Five CMS B - lines and 30 testers were used for morphological and AFLP marker genetic divergence analysis. 150 hybrids were synthesized through Line × Tester (5 × 30) mating design and were used to estimate the mid-parent heterosis for nine characters at two locations. 35 parents were examined for nine morphological traits and were grouped in to six clusters. These parents were also examined for eight AFLP primers combinations and were grouped into seven clusters. More than 50% of hybrids showed significant mid-parent heterosis for both green and red fruit yield plant-1. Hence, there is a much potential for development of good yielding hybrids. The positive significant correlation was found between morphological and AFLP marker distance of the parents with heterosis for plant height (r = 0.17 and 0.38), green fruit yield plant-1 (r = 0.19 and 0.25) and red fruit yield plant-1 (r = 0.20 and 0.34); however, the correlation coefficients were not strong in these traits. Genetic distance between parents was not strong enough to predict the performance of the hybrids and proved to be of no predictive value.Keywords: Correlation, molecular markers, genetic diversity, chill

Novel KRIT1/CCM1 mutation in a patient with retinal cavernous hemangioma and cerebral cavernous malformation

Retinal cavernous hemangiomas are rare vascular anomalies, and can be associated with cerebral cavernous malformations (CCM). Distinct mutations have been reported in patients who have both CCMs and retinal cavernous hemangiomas. Fluorescein angiography, spectral domain optical coherence tomography, and genetic testing were performed on a patient with a retinal cavernous hemangioma and a CCM. Our patient was heterozygous in the KRIT1/CCM1 gene for a frameshift mutation, c.1088delC. This would be predicted to result in premature protein termination. We have identified a novel mutation in the KRIT1/CCM1 gene in a patient with both CCM and retinal cavernous hemangioma. We hypothesize that the occurrence of retinal cavernous hemangiomas and CCMs is underlaid by a common mechanism present in the KRIT1/CCM1 gene

Simultaneous whole-animal 3D-imaging of neuronal activity using light field microscopy

3D functional imaging of neuronal activity in entire organisms at single cell level and physiologically relevant time scales faces major obstacles due to trade-offs between the size of the imaged volumes, and spatial and temporal resolution. Here, using light-field microscopy in combination with 3D deconvolution, we demonstrate intrinsically simultaneous volumetric functional imaging of neuronal population activity at single neuron resolution for an entire organism, the nematode Caenorhabditis elegans. The simplicity of our technique and possibility of the integration into epi-fluoresence microscopes makes it an attractive tool for high-speed volumetric calcium imaging.Comment: 25 pages, 7 figures, incl. supplementary informatio

Target product profiles for protecting against outdoor malaria transmission.

BACKGROUND\ud \ud Long-lasting insecticidal nets (LLINs) and indoor residual sprays (IRS) have decimated malaria transmission by killing indoor-feeding mosquitoes. However, complete elimination of malaria transmission with these proven methods is confounded by vectors that evade pesticide contact by feeding outdoors.\ud \ud METHODS\ud \ud For any assumed level of indoor coverage and personal protective efficacy with insecticidal products, process-explicit malaria transmission models suggest that insecticides that repel mosquitoes will achieve less impact upon transmission than those that kill them outright. Here such models are extended to explore how outdoor use of products containing either contact toxins or spatial repellents might augment or attenuate impact of high indoor coverage of LLINs relying primarily upon contact toxicity.\ud \ud RESULTS\ud \ud LLIN impact could be dramatically enhanced by high coverage with spatial repellents conferring near-complete personal protection, but only if combined indoor use of both measures can be avoided where vectors persist that prefer feeding indoors upon humans. While very high levels of coverage and efficacy will be required for spatial repellents to substantially augment the impact of LLINs or IRS, these ambitious targets may well be at least as practically achievable as the lower requirements for equivalent impact using contact insecticides.\ud \ud CONCLUSIONS\ud \ud Vapour-phase repellents may be more acceptable, practical and effective than contact insecticides for preventing outdoor malaria transmission because they need not be applied to skin or clothing and may protect multiple occupants of spaces outside of treatable structures such as nets or houses

Dense Matter in Compact Stars: Theoretical Developments and Observational Constraints

We review theoretical developments in studies of dense matter and its phase structure of relevance to compact stars. Observational data on compact stars, which can constrain the properties of dense matter, are presented critically and interpreted.Comment: Annu. Rev. Nucl. & Part. Sci. in press. 51 pages, 17 figure

The Interstellar Medium In Galaxies Seen A Billion Years After The Big Bang

Evolution in the measured rest frame ultraviolet spectral slope and ultraviolet to optical flux ratios indicate a rapid evolution in the dust obscuration of galaxies during the first 3 billion years of cosmic time (z>4). This evolution implies a change in the average interstellar medium properties, but the measurements are systematically uncertain due to untested assumptions, and the inability to measure heavily obscured regions of the galaxies. Previous attempts to directly measure the interstellar medium in normal galaxies at these redshifts have failed for a number of reasons with one notable exception. Here we report measurements of the [CII] gas and dust emission in 9 typical (~1-4L*) star-forming galaxies ~1 billon years after the big bang (z~5-6). We find these galaxies have >12x less thermal emission compared with similar systems ~2 billion years later, and enhanced [CII] emission relative to the far-infrared continuum, confirming a strong evolution in the interstellar medium properties in the early universe. The gas is distributed over scales of 1-8 kpc, and shows diverse dynamics within the sample. These results are consistent with early galaxies having significantly less dust than typical galaxies seen at z<3 and being comparable to local low-metallicity systems.Comment: Submitted to Nature, under review after referee report. 22 pages, 4 figures, 4 Extended Data Figures, 5 Extended Data table

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses