Tumor MK2 transcript levels are associated with improved response to chemotherapy and patient survival in non-small cell lung cancer.

Non-small cell lung cancers (NSCLCs) demonstrate intrinsic resistance to cell death, even after chemotherapy. Previous work suggested defective nuclear translocation of active caspase-3 in observed resistance to cell death. We have identified mitogen-activated protein kinase-activated protein kinase 2 (MK2; encoded by the gene MAPKAPK2) is required for caspase-3 nuclear translocation in the execution of apoptosis in endothelial cells. The objective was to determine MK2 expression in NSCLCs and the association between MK2 and clinical outcomes in patients with NSCLC. Clinical and MK2 mRNA data were extracted from two demographically distinct NSCLC clinical cohorts, North American (The Cancer Genome Atlas, TCGA) and East Asian (EA). Tumor responses following first round of chemotherapy were dichotomized as clinical response (complete response, partial response, and stable disease) or progression of disease. Multivariable survival analyses were performed using Cox proportional hazard ratios and Kaplan-Meier curves. NSCLC exhibited lower MK2 expression than SCLC cell lines. In patients, lower tumor MK2 transcript levels were observed in those presenting with late-stage NSCLC. Higher MK2 expression was associated with clinical response following initial chemotherapy and independently associated with improved 2-yr survival in two distinct cohorts, 0.52 (0.28-0.98) and 0.1 (0.01-0.81), TCGA and EA, respectively, even after adjusting for common oncogenic driver mutations. Survival benefit of higher MK2 expression was unique to lung adenocarcinoma when comparing across various cancers. This study implicates MK2 in apoptosis resistance in NSCLC and suggests prognostic value of MK2 transcript levels in patients with lung adenocarcinoma.

MK2 nonenzymatically promotes nuclear translocation of caspase-3 and resultant apoptosis.

We have previously identified mitogen-activated protein kinase-activated protein kinase 2 (MK2) is required for caspase-3 nuclear translocation in the execution of apoptosis; however, little is known of the underlying mechanisms. Therefore, we sought to determine the role of kinase and nonkinase functions of MK2 in promoting nuclear translocation of caspase-3. We identified two non-small cell lung cancer cell lines for use in these experiments based on low MK2 expression. Wild-type, enzymatic and cellular localization mutant MK2 constructs were expressed using adenoviral infection. Cell death was evaluated by flow cytometry. In addition, cell lysates were harvested for protein analyses. Phosphorylation of caspase-3 was determined using two-dimensional gel electrophoresis followed by immunoblotting and in vitro kinase assay. Association between MK2 and caspase-3 was evaluated using proximity-based biotin ligation assays and co-immunoprecipitation. Overexpression of MK2 resulted in nuclear translocation of caspase-3 and caspase-3-mediated apoptosis. MK2 directly phosphorylates caspase-3; however, phosphorylation status of caspase-3 or MK2-dependent phosphorylation of caspase-3 did not alter caspase-3 activity. The enzymatic function of MK2 was dispensable in nuclear translocation of caspase-3. MK2 and caspase-3 associated together and a nonenzymatic function of MK2, chaperoned nuclear trafficking, is required for caspase-3-mediated apoptosis. Taken together, our results demonstrate a nonenzymatic role for MK2 in the nuclear translocation of caspase-3. Furthermore, MK2 may function as a molecular switch in regulating the transition between the cytosolic and nuclear functions of caspase-3.

Changes in fatty acids in Brassica juncea L. oil grown under two simulated conditions of fluoride contamination.

Rapeseed, the second-most-important vegetable oil source, is cultivated in various areas of India where both groundwater and soil are contaminated with fluoride (F-). Furthermore, the frequent use of F- contaminated groundwater for irrigation leads to accumulation of F- in surface and sub-surface soil. The study aims to compare the morphological and biochemical changes in Brassica juncea L., the variations in its fatty acids (FAs) composition and oil yield, under two regimes of F- contaminated soils: (i) pre-contaminated soil (Tr) and (ii) irrigation with F- contaminated water (Ir). The level of F- (µg g-1) in the plant tissues (root, leaf, and grain) was significantly higher in Ir_10 (18.3, 14.7, and 2.8, respectively) than in Tr_10 (4.3, 2.6, and 0.77, respectively), while the oil yield was significantly lower with Ir_10 (19.5%) than with Tr_10 (44.9%). The phytoremediation potential of F- by Brassica juncea L. is greater in Tr regime than in the Ir regime. The erucic acid content (%), which is detrimental to cardiac health, increased to 67.37% (Ir_10) and 58.3% (Tr_10) from 57.73% (control). Thus, the present study shows that irrigation with F- contaminated water results in greater toxicity and accumulation in plants and is not safe for human health.

Irrigation with F^­ contaminated water results in a greater accumulation of F^­ in mustard than cultivated on pre-contaminated soil. The level of erucic acid in mustard oil enhances against F^­ exposure.

Spatio-temporal variation of fluoride in groundwater and agricultural soil and crops of Unnao district, UP: Monitoring and assessment.

Fluoride (F-) contamination in groundwater of Unnao district, Uttar Pradesh was reported for the first time in 1994, however comprehensive monitoring of F- in different environmental matrices remains to be undertaken. The presented study reports spatio-temporal monitoring of F- content in groundwater, crops and soil from F- affected district Unnao, in pre-monsoon (PRM), monsoon (MO) and post-monsoon (PMO), to establish F- groundwater-soil-plant continuum. More than 80% of groundwater samples were contaminated with F-> 1.0 mg L-1 with highest level (mg L-1), at Patiyara (3.6 ± 0.64), during PRM > Pathakpur (2.73 ± 0.57) during PMO > Sarukheda (2.40 ± 0.43) during PRM. High Cr in groundwater was observed in Jajmau (7.08 ± 1.42). The level of F- (mg Kg-1) in agricultural soils followed 3.4 ± 0.71 at Patiyara (MO) > 2.9 ± 0.14 at Badlikheda (PRM) 1.89 ± 0.28 at Jagatkhera (PRM). Among the different edible parts of crops in selected sites, highest F- content (mg Kg-1), F- level in grains of Oryza sativa ranged between 0.23 ± 0.02 to 2.01 ± 0.24. Whereas in the edible fruit of Trichosanthes diocia contained 1.47 ± 0.32 and Momordica charantia 1.47 ± 0.02. Leaf of spinach (1.03 ± 0.22) and seed of Brassica juncea (0.73 ± 0.08). Overall, comparing across all the three seasons, level of F- was highest in all the plants during MO, as compared to PRM and PMO. The regression analysis of physiochemical properties of groundwater show negative relationship between Na+ and F- whereas soil alkalinity exhibited strong influence in soil F-. The high F- content in soil and groundwater at Patiyara and Shekhpur also coincided with presence of several brick kilns, possibly contributing to the high F-.

Nickel and cadmium phytoextraction efficiencies of vetiver and lemongrass grown on Ni-Cd battery waste contaminated soil: A comparative study of linear and nonlinear models.

A comparative assessment of the phytoremediation efficiency of two tolerant grass species viz. vetiver and lemongrass were performed in pots against simulated Ni-Cd battery electrolyte waste (EW) contaminated soil (EW1%, EW2% and EW4% w/w). Ni (µg g-1) accumulation was higher in shoots (36.8) and roots (252.9) of vetiver than in lemongrass (12.5 and 79.7, respectively). While the same trend was true for Cd (µg g-1) accumulation in vetiver and lemon grass roots (232.2 and 147.2, respectively), however, the accumulation in vetiver shoot (43.4) was less than in lemongrass (99.9). The bioaccumulation factor of metals in both grasses increased with EW contamination. Vetiver was tolerant towards EW toxicity than lemongrass, as it exhibited lesser decline in morphological parameters, lesser rise in TBARS against the doses of EW. The activities of SOD, APX, POD enzymes were higher in vetiver whereas, only GR in lemongrass. Multiple linear regression model show, pH had strong and positive influence over the Ni and Cd uptake by the plants whereas, phosphate, OM and bioavailable metals influenced negatively. The higher R2 (>0.9) and Chi-square values ≤ 1 in sigmoid non-linear model demonstrates robustness of the model for predicting the Ni and Cd accumulation (MHM) in both the grasses. Ni accumulation was higher than Cd, roots had greater accumulation of heavy metal and vetiver was a greater accumulator of Ni and Cd from EW the contaminated soil than lemongrass.

GABA mediated reduction of arsenite toxicity in rice seedling through modulation of fatty acids, stress responsive amino acids and polyamines biosynthesis.

γ-aminobutyric acid (GABA) is a free amino acid, which helps to counteract biotic and abiotic stresses in plants. In the present study, two concentrations of GABA, i.e., 0.5 mM and 1 mM were applied to examine the tolerance of rice seedlings against As(III) (25 µM) toxicity, through the modulations of fatty acids (FAs), stress responsive amino acids (AAs) and polyamines (PAs) biosynthesis. Exogenous GABA (0.5 mM) application significantly reduced the H2O2 and TBARS levels and recovered the growth parameters against As(III) stressed rice seedlings. Simultaneously, co-application of GABA (0.5 and 1 mM) and As(III), consistently enhanced the level of unsaturated fatty acids (USFA) (cis-10-pentadecanoic acid, oleic acid, α-linolenic acid and γ-linolenic acid), which was higher than saturated fatty acid (SFA). Among the USFAs, level of linolenic acid was found to be always higher with GABA application. Similarly, elevated level of AAs (proline, methionine, glutamic acid and cysteine) was also observed with the application of GABA (0.5 and 1 mM) in As(III) stressed seedlings. GABA also enhanced the expression of genes involved in the polyamine synthesis pathway namely arginine decarboxylase (AD), spermine (SPM) and spermidine (SPD) synthase against As(III) treatments, which was higher in roots than in shoots, resulting in enhanced root PAs level. Contrarily, the expression of S-adenosylmethionine decarboxylase (S-AMD) was significantly higher in shoots. Among all the PAs, level of putrescine (PUT) was found to be highest with GABA application. Overall, the study demonstrates that GABA (0.5 mM) at lower concentration plays a vital role in As(III) tolerance by enhancing the biosynthesis of USFA, AA and PA, reducing the level of TBARS and H2O2 in rice seedlings.

The Adolescent Girls' Anaemia Control Programme: a decade of programming experience to break the inter-generational cycle of malnutrition in India.

OBJECTIVE: To document the scale-up of India's Adolescent Girls' Anaemia Control Programme following a knowledge-centred framework for scaling up nutrition interventions and to identify the critical elements of and lessons learned from a decade of programme experience for the control of anaemia in adolescent girls. DESIGN: We reviewed all articles, programme and project reports, and baseline and endline assessments published between 1995 and 2012 regarding the control of anaemia through intermittent iron and folic acid supplementation; key programme specialists and managers were interviewed to complete or verify information wherever needed. SETTING: India. SUBJECTS: Adolescent girls. RESULTS: The scale-up of India's Adolescent Girls' Anaemia Control Programme followed a knowledge-centred programme cycle comprising five phases: Evidence, Innovation, Evaluation, Replication and Universalization. By the end of 2011, the programme was being rolled out in thirteen states and was reaching 27.6 million adolescent girls of whom 16.3 million were school-going girls and 11.3 million were out-of-school girls. Building on the critical elements of and lessons learned from the programme, the Government of India launched in 2012 the national Weekly Iron and Folic Acid Supplementation (WIFS) programme to universalize the benefits of anaemia control to the overall population of Indian adolescents. CONCLUSIONS: The Adolescent Girls' Anaemia Control Programme in India provides a good example of how a knowledge-centred approach can successfully guide the scaling up of public health nutrition interventions and facilitate intersectoral convergence among different government departments and development partners to break the inter-generational cycle of undernutrition and deprivation.

The effect of intraoperative specimen inking on lumpectomy re-excision rates.

BACKGROUND: Lumpectomy re-excision to obtain negative margins is common. We compare the effect of two specimen orientation approaches on lumpectomy re-excision rates. METHODS: All women undergoing lumpectomy for breast cancer by a single surgeon between 03/2007 - 02/2009 were included. Lumpectomies underwent standard inking (SI) after surgery by a pathologist from 03/2007-02/2008 while intraoperative inking (II) with direct surgeon input was done from 03/2008-02/2009. Rates of margin positivity and re-excision were compared between these methods. RESULTS: 65 patients were evaluated, reflecting SI in 39 and II in 26 cases. Margin positivity rates of 46% [SI] vs. 23% [II] (p = 0.06) and re-excision rates of 38% [SI] vs. 19% [II] were observed. Residual disease at re-excision was found in 27% [SI] vs. 67% [II] of cases. CONCLUSIONS: Intraoperative inking in this practice offered a simple way to reduce re-excision rates after lumpectomy and affect an improvement in quality of patient care.

Impact of FDA Updates on Public Interest in Breast Implant-associated Anaplastic Large Cell Lymphoma.

In the United States, the Food and Drug Administration (FDA) is responsible for protecting the public health by assuring the safety, efficacy, and security of drugs, biological products, and medical devices. In that role, FDA releases timely updates with regard to medical devices and their possible adverse effects. However, the impact of such FDA updates on public interest has not been studied. The timing of multiple FDA updates regarding Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) was noted from September 2014 to September 2019. Impact on Public interest related to ALCL was measured using Google Trends and the number of YouTube video uploads. These objective markers were used to compare the public interest during FDA updates versus weeks with no FDA updates. Five major updates were released by FDA regarding BIA-ALCL during the past 5 years. Google Trends demonstrated a significant increase in public interest regarding ALCL during the week of FDA release, with a mean score of 69 ± 20.82 when compared with a mean score of 10.68 ± 4.71 (P < 0.001) during weeks with no FDA release. The mean number of YouTube videos uploaded during the period of FDA release was 11.8 ± 9.42, which was significantly higher than the mean of 2.42 ± 1.31 videos (P < 0.001) during the period of no FDA updates. FDA updates correlates with temporal increase in public interest. Plastic surgeons should be aware of FDA information releases on BIA-ALCL and anticipate an increased interest in additional information from patients and the public.

Fluoride distribution and contamination in the water, soil and plants continuum and its remedial technologies, an Indian perspective- a review.

Fluorine is an essential element required in trace amounts but gets toxic for human beings at levels more than 1.5 mg F- L-1 primarily through drinking contaminated water. It is the 13th most abundant element and constitutes about 0.06-0.09% in the earth crust. It is electronegative in aqueous medium forming fluoride ion (F-). Fluoride contamination in the environment occurs mostly due to anthropogenic and geogenic sources. Fluoride is widely distributed in all components of environment, air (0.1-0.6 µg L-1) soils (150-400 mg Kg-1) rocks (100-2000 mg Kg-1), plant (0.01-42 mg Kg-1) and water (1.0-38.5 mg L-1). Human beings and animals are being exposed to F- primarily from water (0.2-42.0 mg L-1) and plants (0.77-29.5 µg g-1). Fluorosis, a health hazard due to F- is a major problem in many countries across the world affecting about 200 million people globally. In India, > 62 million people in twenty states are facing problem due to F-. The most affected states are Rajasthan (7670 habitations), Telangana (1,174 habitations) and Karnataka (1122 habitations). To mitigate this problem, there is an urgent need to understand the current status and brief knowledge of F- geochemistry. The objective of this review is to highlight different sources of F- that contaminate different environmental matrices including plants, the extent of contamination level in India, uptake, translocation and toxicity mechanism in plants. The review also highlights currently available mitigation methods or technologies through physio-chemical and biological means.

Laparoscopic repair of iatrogenic diaphragmatic hernia following radiofrequency ablation for hepatocellular carcinoma.

Radiofrequency ablation (RFA) is commonly used for treating unresectable hepatic malignancies. Some commonly associated complications of RFA include fever, symptomatic pleural effusion, abscess, hepatoma and hepatic insufficiency. Here, we report a case of diaphragmatic hernia in a patient following RFA for hepatic malignancy with cirrhosis.

Pseudointraductal papillary mucinous neoplasia caused by microscopic periductal endocrine tumors of the pancreas: a report of 3 cases.

Intraductal papillary mucinous neoplasms constitute histologically distinctive pancreatic tumors characterized by cystically dilated pancreatic ducts lined by papillary epithelium, often with extensive mucin production. With increasing awareness of and vigilance for these tumors, there has been a surge in the incidence of intraductal papillary mucinous neoplasms in the last few decades. However, resections of presumed intraductal papillary mucinous neoplasms sometimes reveal other types of cystic lesions. Here we describe 3 cases of small, incidentally identified pancreatic endocrine tumors that focally compressed the main pancreatic duct and presented clinically, radiologically, and grossly as intraductal papillary mucinous neoplasm. The histology of the dilated ducts in all cases lacked convincing features of intraductal papillary mucinous neoplasm, prompting more careful examination of the specimens and eventual identification of small well-differentiated endocrine neoplasms. The constellation of findings represented by pancreatic endocrine neoplasm-associated duct stricture and dilatation can mimic intraductal papillary mucinous neoplasm clinically and pathologically. Awareness of this phenomenon can potentially avoid misdiagnosis of intraductal papillary mucinous neoplasm in such cases.

Cell cycle inhibition and apoptosis induced by curcumin in Ewing sarcoma cell line SK-NEP-1.

Curcumin is a naturally occurring polyphenolic compound found in the turmeric, which is used as food additive in Indian cooking and as a therapeutic agent in traditional Indian medicine. Curcumin is currently under investigation as a chemotherapeutic and chemopreventive agent in adult cancer models at both pre-clinical and clinical levels. In this preliminary study, we show that curcumin is effective in causing cell cycle arrest, inducing apoptosis, and suppressing colony formation in the Ewing sarcoma cell line SK-NEP-1. Curcumin causes upregulation of cleaved caspase 3 and downregulation of phospho-Akt, producing apoptosis in Ewing sarcoma cells at an inhibitory concentration 50% (IC50) of approximately 4 µM. Our findings indicate a need for further evaluation of curcumin in chemotherapy and chemoprevention of Ewing sarcoma.

YouTube as a source of information on the H1N1 influenza pandemic.

BACKGROUND: The ongoing H1N1 influenza pandemic has created a significant amount of health concern. Adequate dissemination of correct information about H1N1 influenza could help in decreasing the disease spread and associated anxiety in the population. PURPOSE: This study aims to examine the effective use of the popular Internet video site YouTube as an information source during the initial phase of the H1N1 outbreak. METHODS: YouTube was searched on June 26, 2009, using the keywords swine flu, H1N1 influenza, and influenza for videos uploaded in the past 3 months containing relevant information about the disease. The videos were classified as useful, misleading, or as news updates based on the kind of information contained. Total viewership, number of days since upload, total duration of videos, and source of upload were noted. RESULTS: A total of 142 videos had relevant information about H1N1 influenza. In all, 61.3% of videos had useful information about the disease, whereas 23% were misleading. Total viewership share of useful videos was 70.5%, whereas that of misleading videos was 17.5%, with no significant difference in viewership/day. The CDC contributed about 12% of the useful videos, with a significant viewership share of 47%. No significant differences were seen in viewership/day for useful videos based on the kind of information they contained. CONCLUSIONS: YouTube has a substantial amount of useful information about H1N1 influenza. A source-based preference is seen among the viewers, and CDC-uploaded videos are being used in an increasing proportion as a source of authentic information about the disease.

Occupational exposures and Hodgkin Lymphoma: Canadian case-control study.

OBJECTIVE: The objective was to study the association between Hodgkin Lymphoma (HL) and occupational exposures related to long-held occupation among males in Canada. METHODS: A population-based case-control study of HL was conducted among males stratified by province of residence and age group. Conditional logistic regression was used to fit statistical models. RESULTS: Several factors independently increased the risk of HL. Ever exposure to ionizing radiation from uranium showed a significant association with HL. Men who had smoked cigarettes for 25 years or more were the most likely to develop HL. Exposure to ultraviolet light and diagnosis with measles were negatively associated with HL, whereas diagnosis with shingles increased the risk of HL. CONCLUSIONS: The higher risk of developing HL may be associated with exposure to uranium ionizing radiation and years of cigarette smoking.

Paradoxical payoffs: migrant women, informal sector work, and HIV/AIDS in South Africa.

In post-apartheid South Africa, there has been a significant rise in women's out-migration from rural areas and across its territorial borders for economic purposes resulting in gender reconfiguration of migration streams. Alongside, there has been a simultaneous increase in the participation of women in the labor force. However, this has mostly grown in the informal sector,1 which is often associated with low earnings and insecure working conditions. One consequence has been the increasing reliance of migrant women on survivalist activities such as informal sexual exchanges that increase their risk of contracting HIV infection. Insecure working environments also expose migrant women to sexual abuses. This article is based on the author's work in South Africa's major urban centers and examines the nature of the relationship between the increased migration of black African women in South Africa, the nature of their work, and their resultant vulnerability to HIV/AIDS.