Visual Inspection with Acetic Acid (VIA) Screening Program: 7 Years Experience in Early Detection of Cervical Cancer and Pre-Cancers in Rural South India

Cervical cancer continues to be a major public health problem in India in the absence of wide spread organised cervical screening programs. Visual inspection of the cervix with acetic acid (VIA) is an effective, inexpensive screening test that can be combined with simple treatment procedures for early cervical lesions, provided by trained health workers. We report 7 years experience in early detection of cervical cancer and pre-cancers using the VIA test in a community-based program in rural Andhra Pradesh, India where there are no existing organised cervical screening programs.

Materials and Methods:

Eligible women aged between 26 and 60 were opportunistically screened by trained health wor kers using the VIA test. Women who tested positive were further evaluated and those with cervical lesions were treated either by cryotherapy in the screening clinic or referred to a higher center.

Results:

A total of 18,869 women were screened by a single round of VIA testing with a positive rate of 10.75%. Biopsy proven high-grade squamous intraepithelials (HSILs) were 90 (0.48%) and low-grade squamous intraepithelials (LSILs) were 43 (0.28%). The overall prevalence of cervical intraepithelial neoplasia (CIN) 2+ lesion rate is 1.05%. A total of 312 (1.65%) cryotherapies were done and 49 women underwent hysterectomy.

Conclusions:

VIA by trained female health workers is a safe, acceptable, and effective test that can save lives from cervical cancer even in remote areas with few resources. These results have important implications for efficient service delivery in cervical screening programs in low-resourced settings.     

Sample Matrix Interference in Immunoassays for Organochlorine Residues in Plant-derived Foods and Some Strategies for Their Removal

Immunoassays for two groups of organochlorine insecticides, cyclodienes (endosulfan and heptachlor) and DDT were applied to the analysis of a diverse range of plant-derived foods. Water-miscible solvent extracts of high-moisture, low-fat foods such as cauliflower, cabbage, green and red blue grapes and tomato caused little or no interference with the assays, enabling methanol or acetonitrile extracts of the foods to be analysed directly by immunoassay, after dilution in assay buffer. Reasonable recoveries of spikes of these pesticides were obtained by direct analysis of extracts of spiked commodities, with reliable detection down to 0.025 mg kg^-1 heptachlor or endosulfan and 0.1 mg kg^-1 DDT in the commodities. Acetonitrile extracts of milk could also be analysed directly for DDT. In contrast, extracts of low moisture, non-fatty (rice) and fatty (cottonseed) food commodities interfered appreciably with the assays, reducing assay colour and detection sensitivity. Some simple cleanup methods were developed to remove interference and enable detection of spiked organochlorines in these foods. Extracts of coloured foods, such as tea, coffee and spinach caused similarly major interference in the assays, and a number of simple clean-up methods were ineffective in removing interference. However, use of an immunoaffinity chromatography method for cyclodienes enabled quantitative recoveries to be obtained in extracts of several of these foods when analysed by either ELISA or gas chromatography. Direct analysis was suited for screening purposes but immunoaffinity chromatography results were more quantitative. These results indicate that ELISAs can be applied under developing country conditions to a range of diverse foods, but that cleanup strategies need to be tailored to different types of foods.     

Hierarchical non‐negative matrix factorization to characterize brain tumor heterogeneity using multi‐parametric MRI

Tissue characterization in brain tumors and, in particular, in high‐grade gliomas is challenging as a result of the co‐existence of several intra‐tumoral tissue types within the same region and the high spatial heterogeneity. This study presents a method for the detection of the relevant tumor substructures (i.e. viable tumor, necrosis and edema), which could be of added value for the diagnosis, treatment planning and follow‐up of individual patients. Twenty‐four patients with glioma [10 low‐grade gliomas (LGGs), 14 high‐grade gliomas (HGGs)] underwent a multi‐parametric MRI (MP‐MRI) scheme, including conventional MRI (cMRI), perfusion‐weighted imaging (PWI), diffusion kurtosis imaging (DKI) and short‐TE ¹H MRSI. MP‐MRI parameters were derived: T₂, T₁ + contrast, fluid‐attenuated inversion recovery (FLAIR), relative cerebral blood volume (rCBV), mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK) and the principal metabolites lipids (Lip), lactate (Lac), N‐acetyl‐aspartate (NAA), total choline (Cho), etc. Hierarchical non‐negative matrix factorization (hNMF) was applied to the MP‐MRI parameters, providing tissue characterization on a patient‐by‐patient and voxel‐by‐voxel basis. Tissue‐specific patterns were obtained and the spatial distribution of each tissue type was visualized by means of abundance maps. Dice scores were calculated by comparing tissue segmentation derived from hNMF with the manual segmentation by a radiologist. Correlation coefficients were calculated between each pathologic tissue source and the average feature vector within the corresponding tissue region. For the patients with HGG, mean Dice scores of 78%, 85% and 83% were obtained for viable tumor, the tumor core and the complete tumor region. The mean correlation coefficients were 0.91 for tumor, 0.97 for necrosis and 0.96 for edema. For the patients with LGG, a mean Dice score of 85% and mean correlation coefficient of 0.95 were found for the tumor region. hNMF was also applied to reduced MRI datasets, showing the added value of individual MRI modalities. Copyright © 2015 John Wiley & Sons, Ltd.     

The correlation between ancestry and color in two cities of Northeast Brazil with contrasting ethnic compositions

The degree of admixture in Brazil between historically isolated populations is complex and geographically variable. Studies differ as to what the genetic and phenotypic consequences of this mixing have been. In Northeastern Brazil, we enrolled 522 residents of Salvador and 620 of Fortaleza whose distributions of self-declared color were comparable to those in the national census. Using the program Structure and principal components analysis there was a clear correlation between biogeographic ancestry and categories of skin color. This correlation with African ancestry was stronger in Salvador (r=0.585; P<0.001) than in Fortaleza (r=0.236; P<0.001). In Fortaleza, although self-declared blacks had a greater proportion of European ancestry, they had more African ancestry than the other categories. When the populations were analyzed without pseudoancestors, as in some studies, the relationship of ‘race'' to genetic ancestry tended to diffuse or disappear. The inclusion of different African populations also influenced ancestry estimates. The percentage of unlinked ancestry informative markers in linkage disequilibrium, a measure of population structure, was 3–5 times higher in both Brazilian populations than expected by chance. We propose that certain methods, ascertainment bias and population history of the specific populations surveyed can result in failure to demonstrate a correlation between skin color and genetic ancestry. Population structure in Brazil has important implications for genetic studies, but genetic ancestry is irrelevant for how individuals are treated in society, their health, their income or their inclusion. These track more closely with perceived skin color than genetic ancestry.     

Association of HLA antigens with differential responsiveness toMycobacterium w vaccine in multibacillary leprosy patients

Leprosy patients undergoing phase II trials in two hospitals of New Delhi, India, were HLA typed to see the association of HLA with differential responsiveness toMycobacterium w vaccine. The vaccine comprises an atypical, nonpathogenic mycobacterium,Mycobacterium w, which has cross-reactive antigens withM. leprae. Multibacillary patients who are lepromin negative are vaccinated at an interval of 3 months. Considerable improvement is evident in the patients in terms of a decline in bacterial indices and histopathological and immunological upgrading. But all the patients do not respond to the vaccine in the same manner; some are slow responders, while others are good responders. HLA-A28 and DQw3 (DQw8+9) were found to be associated with slow responsiveness, while DQw1 and DQw7 were found to be associated with a more rapid responsiveness to theM. w vaccine. However, these associations were not significant afterP correction for the number of antigens tested for each locus except for HLA-DQw3 (DQw8 and DQw9) and DQw7. DQw7, a new defined split of HLA-DQw3, seems to be associated with the responsiveness toM. w vaccine.     

Do human leukocyte antigens have a role to play in differential manifestation of multibacillary leprosy: A study on multibacillary leprosy patients from North India

118 multibacillary leprosy patients with differential manifestations were studied for the antigens they expressed at MHC loci to investigate the role of human leukocyte antigens in the differential response to the same causative agent. While the lepromatous leprosy (LL) patients showed a significant increase of Bw60, DR2, DRw8 and DQw1, borderline lepromatous (BL) patients had Bw52, DR9 and DQw7 significantly more often as compared to the normal controls. A comparison of LL, BL and mid-borderline (BB) patients showed a significantly higher frequency of Bw60 in LL patients as compared to the BL. However, Bw52, Bw53, DR9 and DQw7 were found significantly more often in the BL patients as compared to the LL patients but the difference failed to reach significance after pc. A comparison of HLA antigens in BB patients with those of either the LL or BL patients did not show any significant differences.     

Establishment of a formal program for retinoblastoma: Feasibility of clinical coordination across borders and impact on outcome

Retinoblastoma is an ocular tumor that occurs in young children, in either heritable or sporadic manner. The relative rarity of retinoblastoma, and the need for expensive equipment, anesthesia, and pediatric ophthalmologic expertise, are barriers for effective treatment in developing countries. Also, with an average age‐adjusted incidence of two to five cases per million children, patient number limits development of local expertise in countries with small populations. Lebanon is a small country with a population of approximately 4.5 million. In 2012, a comprehensive retinoblastoma program was formalized at the Children's Cancer Institute (CCI) at the American University of Beirut Medical Center, and resources were allocated for efficient interdisciplinary coordination to attract patients from neighboring countries such as Syria and Iraq, where such specialized therapy is also lacking. Through this program, care was coordinated across hospitals and borders such that patients would receive scheduled chemotherapy at their institution, and monthly retinal examinations and focal laser therapy at the CCI in Lebanon. Our results show the feasibility of successful collaboration across borders, with excellent patient and physician adherence to treatment plans. This was accompanied by an increase in patient referrals, which enables continued expertise development. However, the majority of patients presented with advanced intraocular disease, necessitating enucleation in 90% of eyes in unilateral cases, and more than 50% of eyes in bilateral cases. Future efforts need to focus on expanding the program that reaches to additional hospitals in both countries, and promoting early diagnosis, for further improvement of globe salvage rates.