Patterns of basal signaling heterogeneity can distinguish cellular populations with different drug sensitivities

Non small cell lung cancer H460 clones exhibit a high degree of heterogeneity in signaling states.Clones with similar patterns of basal signaling heterogeneity have similar paclitaxel sensitivities.Models of signaling heterogeneity among the clones can be used to classify sensitivity to paclitaxel for other cancer populations

Iminosugar-Based Inhibitors of Glucosylceramide Synthase Increase Brain Glycosphingolipids and Survival in a Mouse Model of Sandhoff Disease

The neuropathic glycosphingolipidoses are a subgroup of lysosomal storage disorders for which there are no effective therapies. A potential approach is substrate reduction therapy using inhibitors of glucosylceramide synthase (GCS) to decrease the synthesis of glucosylceramide and related glycosphingolipids that accumulate in the lysosomes. Genz-529468, a blood-brain barrier-permeant iminosugar-based GCS inhibitor, was used to evaluate this concept in a mouse model of Sandhoff disease, which accumulates the glycosphingolipid GM2 in the visceral organs and CNS. As expected, oral administration of the drug inhibited hepatic GM2 accumulation. Paradoxically, in the brain, treatment resulted in a slight increase in GM2 levels and a 20-fold increase in glucosylceramide levels. The increase in brain glucosylceramide levels might be due to concurrent inhibition of the non-lysosomal glucosylceramidase, Gba2. Similar results were observed with NB-DNJ, another iminosugar-based GCS inhibitor. Despite these unanticipated increases in glycosphingolipids in the CNS, treatment nevertheless delayed the loss of motor function and coordination and extended the lifespan of the Sandhoff mice. These results suggest that the CNS benefits observed in the Sandhoff mice might not necessarily be due to substrate reduction therapy but rather to off-target effects

A comparative evaluation of endemic and non-endemic region of visceral leishmaniasis (Kala-azar) in India with ground survey and space technology

In visceral leishmaniasis, phlebotomine vectors are targets for control measures. Understanding the ecosystem of the vectors is a prerequisite for creating these control measures. This study endeavours to delineate the suitable locations of Phlebotomus argentipes with relation to environmental characteristics between endemic and non-endemic districts in India. A cross-sectional survey was conducted on 25 villages in each district. Environmental data were obtained through remote sensing images and vector density was measured using a CDC light trap. Simple linear regression analysis was used to measure the association between climatic parameters and vector density. Using factor analysis, the relationship between land cover classes and P. argentipes density among the villages in both districts was investigated. The results of the regression analysis indicated that indoor temperature and relative humidity are the best predictors for P. argentipes distribution. Factor analysis confirmed breeding preferences for P. argentipes by landscape element. Minimum Normalised Difference Vegetation Index, marshy land and orchard/settlement produced high loading in an endemic region, whereas water bodies and dense forest were preferred in non-endemic sites. Soil properties between the two districts were studied and indicated that soil pH and moisture content is higher in endemic sites compared to non-endemic sites. The present study should be utilised to make critical decisions for vector surveillance and controlling Kala-azar disease vectors

Teratoma of the lumbosacral region: a case report

<p>Abstract</p> <p>Introduction</p> <p>Teratoma is a tumor that usually arises from one or more germ layers. They are most commonly found in the sacrococcygeal region and have a female preponderance. We present a very rare case of a boy with a benign cystic teratoma in the lumbosacral region.</p> <p>Case presentation</p> <p>A 16-year-old Indian boy presented to our hospital with a history of a lump in the lower back region since birth. Initially, it was small, but its size increased gradually over time to a size of 15 cm × 15 cm at presentation. There were no other associated abnormalities. Investigations revealed the lump to be a benign cystic teratoma. The patient underwent surgery, and the whole tumor, from its base to the vertebrae, was excised. Bisection of the tumor revealed that it contained hair and pultaceous material consistent with a teratoma, which was later confirmed by histopathologic examination.</p> <p>Conclusion</p> <p>Benign cystic teratomas should be diagnosed and managed aggressively because they generally have a greater tendency to progress toward malignancy. After extensively searching the case report database, we arrived at the conclusion that this was a rare case of a benign cystic teratoma in the lumbosacral region in a boy.</p