Correlates of Defaulting from MDT among Leprosy Patients.

In order to analyse the factors of demographic as well as disease related variables and their correlation with Rate of Defaulting (ROD) from Multi Drug Therapy (MDT) among leprosy patients, secondary data have been collected from 3,579 new cases registered for MDT, during a period of 4 years from 2007 to 2010 in four leprosy hospitals/ treatment centers across the four high endemic states viz. Uttar Pradesh, Chhattisgarh; Maharashtra and Andhra Pradesh. Year wise percentage of patients defaulted was calculated on aggregate as well as with reference to each centre and cross tabulated with demographic and disease related factors. Findings show that out of the total 3,579 new cases, 1944,(54.3%) defaulted with variation across centers ranged from 44 to 66 percent. Comparison of ROD against type of leprosy indicated that MB types defaulted (55.7%) more than PB (50.6%) types, (statistically significant difference, (p=0,04). ROD of male patients across the centers ranged from 45% to 67.7% in comparison with 42.4% to 61.5% of female patients. A-statistically significant difference (p=6.04) was found between the overall ROD of males (56.35%) and females (51.47%). The ROD among those with more severe disabilities (WHO Gr-2) ranged between 44% to 67.5% across the centers, while the same among those'with less severe disabilities (Gr-0&1) ranged from 42.6 to 72.7 percent. Comparison of ROD against severity of disability was found statistically significant only across 2 centers. No statistically significant variation was found when ROD of adult patients with refeince to each centr ranged between (43.6% to 65.4%) was compared with the same of children ranged beeIen (36.2% to 69.3%). Across each of these categories and centers,'the ROD remained consistent over the ,4 years. Based on the above findings'this may be concluded that male sex and MB types are significant correlates of default from treatment. Severity of disabilities plays significant role only in certain areas, probably due to other interfering factors, which needs to be further investiged.

Silencing of miR-148a in cancer-associated fibroblasts results in WNT10B-mediated stimulation of tumor cell motility.

The tumor microenvironment has an important role in cancer progression. Here we show that miR-148a is downregulated in 15 out of 16 samples (94%) of cancer-associated fibroblasts (CAFs) compared with matched normal tissue fibroblasts (NFs) established from patients with endometrial cancer. Laser-capture microdissection of stromal cells from normal tissue and endometrial cancer confirmed this observation. Treatment of cells with 5-aza-deoxycytidine stimulated the expression of miR-148a in the majority of CAFs implicating DNA methylation in the regulation of miR-148a expression. Investigation of miR-148a function in fibroblasts demonstrated that conditioned media (CM) from CAFs overexpressing miR-148a significantly impaired the migration of five endometrial cancer cell lines without affecting their growth rates in co-culture experiments. Among predicted miR-148a target genes are two WNT family members, WNT1 and WNT10B. Activation of the WNT/ß-catenin pathway in CAFs was confirmed by microarray analysis of gene expression and increased activity of the SuperTOPFlash luciferase reporter. We found elevated levels of WNT10B protein in CAFs and its level decreased when miR-148a was re-introduced by lentiviral infection. The 3'-UTR of WNT10B, cloned downstream of luciferase cDNA, suppressed luciferase activity when co-expressed with miR-148a indicating that WNT10B is a direct target of miR-148a. In contrast to the effect of miR-148a, WNT10B stimulated migration of endometrial cancer cell lines. Our findings have defined a molecular mechanism in the tumor microenvironment that is a novel target for cancer therapy.

Mass survey of leprosy in Lalitpur district, Nepal.

An intense mass survey of leprosy in Lalitpur District, Nepal, was carried for the period 1986 to 1990. This was the first such large scale survey in Nepal; 85% of the total population was examined. The 5-year case detection rate was 13 per 10,000; the 5-year child detection rate was 4 per 10,000. By the end of the survey the prevalence rate was 6.8 per 10,000; at the end of 1992 this had dropped to 2.2 per 10,000. In 1989, after a 3-year interval, a re-survey was done in three village development committees (VDCs) and 4 new cases were detected, bringing the 3-year case detection rate to 3.3 per 10,000; 36% of the old cases, 20% of the new adult cases, and 3% of the new child cases were classified as multibacillary. Overall, 62.7% of the patients had no disability, 18.8% had disability grade 1, and 12.7% had disability grade 2 while for 5.8% the data were incomplete. By the end of the survey 91% of the patients needing medical treatment were on multidrug therapy (MDT). At present this has increased to 100%. The regularity rate was 86%; at the end of 1992 this had increased to 96%. The cost for detecting one new patient was US$298. Because of the high cost, it is recommended that intense mass surveys not be performed when the estimated prevalence rate is less than 10 per 10,000 inhabitants. From the data collected conclusions were drawn and recommendations were formulated for developing new strategies for the National Leprosy Control Programme of the Government of Nepal.

Comparative kinetics study of the evolution of freshwater aquatic toxicity and biodegradability of linear and branched alkylbenzene sulfonates.

Evolution of both primary biodegradability and acute toxicity to daphnia and zebra fish of a linear alkylbenzene sodium sulfonate (LAS) and a branched alkylbenzene sodium sulfonate (BAS) have been measured simultaneously. In six of eight experiments, LAS was biodegraded to 90% in 7 days and BAS to 70% in 7 days. In the two other experiments, both LAS and BAS have shown the same biodegradation speed and reached the same biodegradation level in 7 days: 45% in one experiment and 55% in the other. The composition of bacteria population and the level of cellular ATP of the inoculum play a decisive role in the biodegradation. These results confirm that it is essential to know the composition of bacteria population present in the inoculum as well as their biochemical characteristics to accurately interpret results of biodegradation tests. In the case of a rapid primary biodegradation of LAS and BAS, the acute toxicity of LAS remains three times as high as that of BAS for at least 24 hr toward daphnia and 48 hr toward zebra fish. Their acute toxicity to daphnia and zebra fish become equivalent only after 72 hr. When primary biodegradation of both products is slower, the acute toxicity of LAS remains higher than that of BAS for more than 7 days.