Anaplastic thyroid cancer is an aggressive and fatal malignancy. Many advanced cancers are characterized by glucose dependency, leading to oxidative stress and cellular proliferation. Therefore, we ...sought to determine if a low glucose environment (in vitro) or a ketogenic diet (in vivo) could inhibit anaplastic thyroid cancer tumor growth when combined with the antioxidant N-acetylcysteine.
In vivo, nude mice were injected with the anaplastic thyroid cancer cell line 8505C (n = 6/group). Group 1 was fed a standard diet; Group 2 was fed a ketogenic diet; Group 3 was given standard diet with N-acetylcysteine (40 mM in the drinking water); and Group 4 was fed ketogenic diet with N-acetylcysteine. Tumor volumes, ketones, and glucose were measured. H&E stains and immunohistochemistry for Ki-67 and Caspase 3 were performed on the tumors. In vitro, 8505C cells were cultured in high glucose (25 mM), low glucose (3 mM), high glucose plus N-acetylcysteine (200 uM), or low glucose plus N-acetylcysteine for 96 hours. We performed CyQUANT proliferation (Thermo Fisher Scientific, Waltham, MA), Seahorse glycolytic stress (Agilent, Santa Clara, CA), and reactive oxidative stress assays.
Ketogenic diet plus N-acetylcysteine decreased in vivo tumor volume compared to standard diet (22.5 ± 12.4 mm3 vs 147 ± 54.4 mm3, P < .05) and standard diet plus N-acetylcysteine (P < .05). Blood ketone levels were significantly higher for the mice in the ketogenic diet group compared to standard diet (1.74 mmol/L vs 0.38 mmol/L at week 5, P < .001). However, blood glucose levels were not significantly different between ketogenic diet and standard diet groups. Cells cultured in low glucose plus N-acetylcysteine had significantly reduced proliferation compared to high glucose (98.1 ± 5.0 relative fluorescence units vs 157.8 ± 2.1 relative fluorescence units, P < .001). Addition of N-acetylcysteine to low glucose lowered glycolysis function compared to high glucose (39.0 ± 2.2 mpH/min/cell vs 89.1 ± 13.2 mpH/min/cell, P < .001) and high glucose plus N-acetylcysteine (37.4 ± 2.5 mpH/min/cell vs 70.3 ± 3.3 mpH/min/cell, P < .001). Low glucose plus N-acetylcysteine decreased reactive oxidative stress compared to high glucose (119 ± 34.7 relative fluorescence units vs 277 ± 16.0 relative fluorescence units, P = .014).
The combination of a ketogenic diet or glucose restriction with the antioxidant- N-acetylcysteine significantly reduced tumor growth in vivo and in vitro. Further studies are warranted to explore these metabolic therapies in anaplastic thyroid cancer.
A national sample survey of leprosy was undertaken in partnership with Indian Council of Medical Research (ICMR) institutions, National Leprosy Eradication Programme (NLEP), Panchayati Raj members, ...and treated leprosy patients to detect new cases of leprosy in India. The objectives of the survey were to estimate the new leprosy case load; record both Grade 1 and Grade 2 disabilities in the new cases; and to assess the magnitude of stigma and discrimination prevalent in the society. A cluster based, cross-sectional survey involving all States was used for the door-to-door survey using inverse sampling methodology. Rural and urban clusters were sampled separately. The population screened for detecting 28 new cases in rural and 30 in urban clusters was enumerated, recorded and analyzed. Data capture and analysis in different schedules were the main tools used. For quality control three tiers of experts were utilized for the confirmation of cases and disabilities. Self-stigma was assessed in more than half of the total new patients detected with disabilities by the approved questionnaire. A different questionnaire was used to assess the stigma in the community. A population of 14,725,525 (10,302,443 rural; 4,423,082 urban) was screened and 2161 new cases - 1300 paucibacillary (PB) and 861 multibacillary (MB) were detected. New case estimates for leprosy was 330,346 (95% Confidence limits, 287,445-380,851). Disabilities observed in these cases were 2.05/100,000 population and 13.9 per cent (302/2161) in new cases. Self-stigma in patients with disabilities was reduced, and the patients were well accepted by the spouse, neighbour, at workplace and in social functions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This paper proposes a data envelopment analysis (DEA)-based portfolio efficiency evaluation approach integrated with a rebalancing method to help investors acquire efficient portfolios. Two fuzzy ...portfolio selection models with value at risk (VaR) and conditional value at risk (CVaR) as objectives are proposed under the credibilistic framework. The models are constrained by realistic constraints of short selling/no short selling, capital budget, bounds on investment in an asset, and minimum return desired by the investor. These models are used to compute the benchmark portfolios, which constitute the portfolio efficient frontier. Furthermore, random sample portfolios are generated individually for each model in compliance with their constraints. These random sample portfolios are evaluated in terms of their relative efficiency with risk (VaR or CVaR) as an input and return as an output using DEA. Bearing in mind the volatile nature of the investment market, negative returns are also considered for portfolio efficiency evaluation using the range directional model. Moreover, an efficiency frontier improvement algorithm is used to rebalance the inefficient random portfolios to make them efficient. The proposed approach provides an alternative to the investors to acquire benchmark portfolios using the traditional portfolio selection models. A detailed numerical illustration and an out of sample analysis with the Nifty 50 index from the National Stock Exchange, India, are presented to substantiate the proposed approach.
Anaplastic thyroid cancer is a rare but devastating malignancy. Anaplastic thyroid cancer cells exhibit the Warburg effect by preferentially undergoing glycolysis even in aerobic conditions, leading ...to high glucose use. Here we assess if targeted inhibition of glycolysis can diminish anaplastic thyroid cancer growth and improve outcomes.
Human anaplastic thyroid cancer cell line 8505C was grown in medium containing high (25 mmol/L) or low (3 mmol/L) glucose concentration and hexokinase II inhibitor 3-bromopyruvate (200 μM). Cellular proliferation, migration, and invasion were measured. An orthotopic xenograft model of anaplastic thyroid cancer was generated in nude mice using 8505C cells. Animals were provided standard chow or a ketogenic diet and treated with 3-bromopyruvate (1.8 mg/kg). Overall survival time was monitored. Necropsies were performed to harvest tumors for analysis.
Growth of 8505C in low-glucose medium with 3-bromopyruvate decreased cell proliferation by 89%, migration by 44%, and invasion by 73% (P < .001 for all) compared with high glucose. Animals concomitantly receiving a ketogenic diet and 3-bromopyruvate exhibited smaller tumor volumes (P = .03), slower tumor growth rates (P = .01), and improved overall survival (P = .006) compared with standard-diet control subjects. Monotherapy with a ketogenic diet or 3-bromopyruvate alone did not reduce tumor size or increase survival over the standard-diet control group.
Glycolytic inhibition with 3-bromopyruvate inhibits tumor growth and extends survival in a murine model of anaplastic thyroid cancer when combined with the ketogenic diet. Thus, targeted glycolytic inhibition of anaplastic thyroid cancer exhibits context-specific utility and may only be effective during ketosis induced by dietary restriction of glycolytic inputs.
Estimation of disease burden due to leprosy by conventional sampling procedure is difficult due to large sample size requirement. In such situation, inverse sampling procedure could be a choice. A ...pilot study was undertaken to study the feasibility of adopting inverse sampling procedure over conventional sampling in an endemic area of Uttar Pradesh, India.
Two community development blocks one with high endemic, namely, Fatehganj, and other low endemic, Ramnagar, in Bareilly district of Uttar Pradesh, India, were selected. The Inverse sampling was adopted in Fatehganj and conventional cluster sampling was used in Ramnagar. As per the design of inverse sampling, 25 new cases of leprosy were to be detected from a population that could provide the cases. Under conventional sampling, a sample of 44,000 subjects (population) was targeted for the survey.
In Fatehganj, 25 new cases of leprosy were detected from a sample of 14734 individuals. In Ramnagar, a total of 63 new cases of leprosy were found after covering a sample of 44686 individuals. Both the techniques provided similar estimates. The precision obtained under inverse sampling was though less than that under conventional sampling but found to be more feasible and suitable for estimation of leprosy due to less population to be covered, time and cost.
Our findings showed reveals that inverse sampling was advantageous over conventional sampling and could be adopted for the large scale survey at national level.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Objective To determine the safety and effectiveness of self-administered treatment with isosorbide mononitrate (IMN) for cervical ripening in Indian women with postdated pregnancies. Methods ...A randomized, placebo-controlled study was conducted with 200 women with postdated pregnancies and unfavorable cervices who self-administered vaginally either 2 40-mg tablets of IMN or 2 40-mg tablets of pyridoxine as placebo prior to admission for induction of labor. The main outcome variables were change in Bishop score, time from admission to delivery, and presence or absence of fetal and maternal morbidity. Results The Bishop score was significantly improved 24 hours after initiation of the outpatient IMN treatment ( P < 0.001) and the needs for further cervical ripening and oxytocin infusion were less in the study than in the control group ( P < 0.001 and P = 0.008). The time from admission to delivery was also less ( P < 0.001). Moreover, the IMN treatment had no major adverse maternal or fetal effects. The vast majority of women in both groups were either satisfied or very satisfied with the outpatient treatment. Conclusion The self-administration, at home, of isosorbide mononitrate leads to a safe and effective cervical ripening prior to labor induction in women with postdated pregnancies. CTRI Registration No.: CTRI/2011/091/000121
Objectives
To compare the incidence of visible strings after postplacental intracesarean insertion of Cu375 and CuT380A intrauterine contraceptive devices (IUD).
Methods
This was a prospective, ...randomized comparative study. A total of 100 women fulfilling the inclusion and exclusion criteria underwent postplacental intracesarean insertion of either Cu375 IUD or CuT380A IUD. Women were followed up at 1, 6 weeks and 3 months after IUD insertion and were questioned about IUD expulsion or removal at each visit. The cervix was inspected to visualize the IUD strings. Data were analyzed by Chi-square test.
Results
At 6-week follow-up, 97.9% women in group A versus 41.7% women in group B had strings visible at the cervical os and at 3 months 100% women in group A versus only 47.9% women in group B (
p
< 0.001) had visible strings of IUD.
Conclusion
Both Cu375 and CuT380A IUD are safe postpartum method of contraception but Cu375 if used for intracesarean IUD insertion increases the incidence of visible IUD strings. Hence, it avoids radiological investigations and invasive procedures at follow-up visits required to locate the IUD when strings are not visible.
CTRI No.
CTRI/2015/09/006221.
Dubey et al. 40 have shown that solving an Atanassov's I-fuzzy Linear Programming Problem represented by Atanassov's I-fuzzy sets with linear membership and non-membership functions is equivalent to ...solving an appropriate fuzzy optimisation problem with piecewise linear S-shaped membership functions. The equivalence is established using Hurwicz optimism-pessimism criterion 38 and indeterminacy resolution in Atanassov's I-fuzzy sets. Moreover, in case of convex break points in the piecewise linear membership function, the crisp counterpart of the equivalent optimisation problem involves binary variables. Here, in this paper we first convert the resulting fuzzy optimisation problem having convex break points into an equivalent fuzzy optimisation problem having concave break points on the lines of Inuiguchi et al. 34, before formulating its crisp equivalent. The advantage of this strategy is that the resulting crisp equivalent problem has no binary variables. Further, we also make use of the indeterminacy factor resolution principle to establish a duality relation which can be interpreted as a Atanassov's I-fuzzy variant of the (crisp) weak duality theorem.
Objective
To evaluate the relationship between maternal age at child birth, and perinatal and under-five mortality.
Design
Prospective birth cohort.
Setting
Urban community.
Participants
9169 ...pregnancies in the New Delhi Birth Cohort resulted in 8181 live births. These children were followed for survival status and anthropometric measurements at birth (+3 days), 3,6,9 and 12 months (7 days), and every 6 months thereafter until 21 years age. Information on maternal age at child birth and socio-demographic profile was also obtained.
Outcome measures
Offspring mortality from 28 weeks gestation till 5 years age.
Results
Offspring mortality (stillbirths–5 years;
n
=328) had a U-shaped association with maternal age (
P
<0.001). Compared to the reference group (20-24 years), younger (≤19 years) and older (≥ 35 years) maternal ages were associated with a higher risk of offspring mortality (HR: 1.68; 95% CI 1.16, 2.43 and HR 1.48; 95% CI 1.01, 2.16, respectively). In young mothers, the increased risk persisted after adjustment for socio-economic confounders (maternal education, household income and wealth; HR 1.51; 95% CI 1.03, 2.20) and further for additional behavioral (place of delivery) and biological mediators (gestation and birthweight) (HR 2.14; 95% CI 1.25,3.64). Similar associations were documented for post-perinatal deaths but for perinatal mortality the higher risk was not statistically significant (
P
>0.05). In older mothers, the increased mortality risk was not statistically significant (
P
>0.05) after adjustment for socio-economic confounders.
Conclusion
Young motherhood is associated with an increased risk of post-perinatal mortality and measures to prevent early childbearing should be strengthened.
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