Prameha purvaroopa as diabetes risk predictor - trends from a retrospective cohort study of newly diagnosed type 2 diabetes patients.

STUDY BACKGROUND: Increasing prevalence of type 2 diabetes has shifted the focus of world from its management to prevention. Life style modifications programs related to diabetes prevention are found to delay the progress of prediabetes into diabetes. Reaching out to community with diabetes prevention program however is still a challenge to meet. OBJECTIVE: Of the study: This study proposed to retrospectively screen the presence of prediabetes symptoms depicted in Ayurveda literature in a newly diagnosed diabetic population and to compare this prevalence with non-diabetic and healthy population. The idea is to put weightage upon prediabetes symptoms as a disease predictor if these are available early in the course of the disease. MATERIAL AND METHODS: A questionnaire based upon detailed literature survey of three Ayurveda classics from the subject area of prameha (identical to diabetes) identified 22 features under the class of prediabetes. A questionnaire was developed to find the presence of these features in selected diabetic population retrospectively before the onset of diabetes. 141 newly diagnosed diabetics were selected on the basis of a defined inclusion and exclusion criteria and surveyed for chronological presence of prediabetes features as identified through the literature search and validated through a validation process. This feature prevalence was further compared with non-diabetic and healthy population. RESULTS: A significant difference (p < 0.001) was observed in specific symptom occurrence in diabetic population comparing to non-diabetic and healthy control for at least 11 of the selected items. CONCLUSION: The study observes that few prediabetes features show their clear retrospective presence in diabetic population comparing to non-diabetic and healthy population. This observation can help formulating a risk calculator for future diabetes on the basis of available pre diabetic features in an individual. A prospective cohort study however would be essential to prove any such realistic relation between prediabetes symptoms and future diabetes development among high risk individuals.

Predicting and preventing diabetes: Translational potential of Ayurveda information on pre-diabetes.

Continued rise in incidence and prevalence of diabetes globally warrants an effective strategy for its prevention and control. Prevention of diabetes seems more logical to attempt seeing its health care burden, long dormancy, systemic affliction and poor general awareness. Pre-diabetes is the intermediate state of erratic glucose metabolism without overt features of diabetes. This state seems to be a crossroad having a possibility to either convert into clinical diabetes, remain dormant or return to normal glucose control depending upon the efforts made. Unfortunately, due to the paucity of apparent clinical symptoms, this state embedded with reversal possibility, remains unexplored. Ayurveda account of prameha purvarupa (subclinical features of diabetes) may be proposed as the foundation upon which clinic-based pre-diabetes identification and subsequent prevention may be explored. Knowing the symptoms for their reliable proximity with upcoming diabetes may turn to be sensible sensitizers prompting the people to abort the disease process in an effective and timely manner. Considering diabetes from its purvarupa to complications as disease continuum and exploring the opportunities to intervene in order to prevent, or manage the disease on the basis of shada kriyaa kaala therefore, has a huge translational potential warrants an urgent exploration.

Interactive Exploration and Visualization Using MetaTracts extracted from Carbon Fiber Reinforced Composites.

This work introduces a tool for interactive exploration and visualization using MetaTracts. MetaTracts is a novel method for extraction and visualization of individual fiber bundles and weaving patterns from X-ray computed tomography (XCT) scans of endless carbon fiber reinforced polymers (CFRPs). It is designed specifically to handle XCT scans of low resolutions where the individual fibers are barely visible, which makes extraction of fiber bundles a challenging problem. The proposed workflow is used to analyze unit cells of CFRP materials integrating a recurring weaving pattern. First, a coarse version of integral curves is used to trace sections of the individual fiber bundles in the woven CFRP materials. We call these sections MetaTracts. In the second step, these extracted fiber bundle sections are clustered using a two-step approach: first by orientation, then by proximity. The tool can generate volumetric representations as well as surface models of the extracted fiber bundles to be exported for further analysis. In addition a custom interactive tool for exploration and visual analysis of MetaTracts is designed. We evaluate the proposed workflow on a number of real world datasets and demonstrate that MetaTracts effectively and robustly identifies and extracts fiber bundles.

Age-dependent IgG subclass responses to Plasmodium falciparum EBA-175 are differentially associated with incidence of malaria in Mozambican children.

Plasmodium falciparum blood-stage antigens such as merozoite surface protein 1 (MSP-1), apical membrane antigen 1 (AMA-1), and the 175-kDa erythrocyte binding antigen (EBA-175) are considered important targets of naturally acquired immunity to malaria. However, it is not clear whether antibodies to these antigens are effectors in protection against clinical disease or mere markers of exposure. In the context of a randomized, placebo-controlled trial of intermittent preventive treatment in infants conducted between 2002 and 2004, antibody responses to Plasmodium falciparum blood-stage antigens in a cohort of 302 Mozambican children were evaluated by immunofluorescence antibody test and enzyme-linked immunosorbent assay at 5, 9, 12, and 24 months of age. We found that IgG subclass responses to EBA-175 were differentially associated with the incidence of malaria in the follow-up period. A double amount of cytophilic IgG1 or IgG3 was associated with a significant decrease in the incidence of malaria (incidence rate ratio [IRR] = 0.49, 95% confidence interval [CI] = 0.25 to 0.97, and P = 0.026 and IRR = 0.44, CI = 0.19 to 0.98, and P = 0.037, respectively), while a double amount of noncytophilic IgG4 was significantly correlated with an increased incidence of malaria (IRR = 3.07, CI = 1.08 to 8.78, P = 0.020). No significant associations between antibodies to the 19-kDa fragment of MSP-1 (MSP-1(19)) or AMA-1 and incidence of malaria were found. Age, previous episodes of malaria, present infection, and neighborhood of residence were the main factors influencing levels of antibodies to all merozoite antigens. Deeper understanding of the acquisition of antibodies against vaccine target antigens in early infancy is crucial for the rational development and deployment of malaria control tools in this vulnerable population.

Curcumin enhances the efficacy of chemotherapy by tailoring p65NFκB-p300 cross-talk in favor of p53-p300 in breast cancer.

Breast cancer cells often develop multiple mechanisms of drug resistance during tumor progression, which is the major reason for the failure of breast cancer therapy. High constitutive activation of NFκB has been found in different cancers, creating an environment conducive for chemotherapeutic resistance. Here we report that doxorubicin-induced SMAR1-dependent transcriptional repression and SMAR1-independent degradation of IkBα resulted in nuclear translocation of p65NFκB and its association with p300 histone acetylase and subsequent transcription of Bcl-2 to impart protective response in drug-resistant cells. Consistently SMAR1-silenced drug-resistant cells exhibited IkBα-mediated inhibition of p65NFκB and induction of p53-dependent apoptosis. Interestingly, curcumin pretreatment of drug-resistant cells alleviated SMAR1-mediated p65NFκB activation and hence restored doxorubicin sensitivity. Under such anti-survival condition, induction of p53-p300 cross-talk enhanced the transcriptional activity of p53 and intrinsic death cascade. Importantly, promyelocyte leukemia-mediated SMAR1 sequestration that relieved the repression of apoptosis-inducing genes was indispensable for such chemo-sensitizing ability of curcumin. A simultaneous decrease in drug-induced systemic toxicity by curcumin might also have enhanced the efficacy of doxorubicin by improving the intrinsic defense machineries of the tumor-bearer. Overall, the findings of this preclinical study clearly demonstrate the effectiveness of curcumin to combat doxorubicin-resistance. We, therefore, suggest curcumin as a potent chemo-sensitizer to improve the therapeutic index of this widely used anti-cancer drug. Taken together, these results suggest that curcumin can be developed into an adjuvant chemotherapeutic drug.

Hyper-expansion of asparagines correlates with an abundance of proteins with prion-like domains in Plasmodium falciparum.

Plasmodium falciparum encodes approximately 5300 proteins of which approximately 35% have repeats of amino acids, significantly higher than in other fully sequenced eukaryotes. The proportion of proteins with amino acid homorepeats varies from 4 to 54% amongst different functional classes of proteins. These homorepeats are dominated by asparagines, which are selected over lysines despite equivalent AT codon content. Surprisingly, asparagine repeats are absent from the variant surface antigen protein families of PfEMP1s, Stevors and Rifins. The PfEMP1 protein family is instead rich in recurrences of glutamates, similar to human cell surface proteins. Structural mapping of homorepeats suggests that these segments are likely to form surface exposed structures that protrude from the main protein cores. We also found an abundance of asparagine-rich prion-like domains in P. falciparum, significantly larger than in any other eukaryote. Domains rich in glutamines and asparagines have an innate predisposition to form self-propagating amyloid fibers, which are involved both in prion-based inheritance and in human neurodegenerative disorders. Nearly 24% (1302 polypeptides) of P. falciparum proteins contain prion-forming or prion-inducing domains, in comparison to Drosophila (approximately 3.4%) which to date showed the highest number of prion-like proteins. The unexpected properties of P. falciparum revealed here open new avenues for investigating parasite biology.