Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Fast seperation and sensitive detection of carcinogenic aromatic amines by reversed phase liquid chromatography coupled with electrochemical detection.

A micro-LC method was developed for the fast and sensitive analysis of aromatic amines by electrochemical detection. The chromatographic separation of nine carcinogenic aromatic amines was performed on an ABZ + PLUS column with detection limits up to pM L(-1) levels. Mobile phase comprised of methanol-acetate buffer of pH 5 (45:55, v/v) used at a flow rate of 0.2 ml min(-1). The detection was performed with a 6 mm glassy carbon electrode at an applied potential of 0.8 V versus Ag/AgCl. An intraday RSD for retention time and peak area were between 0.22% and 0.73% and 1.86% and 4.03%, respectively. The interdays RSD for retention time and peak area were between 0.47% and 1.35% and 2.04% and 4.42%, respectively. The applicability of the assay has been demonstrated by analyzing these aromatic amines in lake water and synthetic food colour additives. A comparison is given between electrochemical and UV detection

Hypoglycemic potential of alcoholic root extract of Cassia occidentalis Linn. in streptozotocin induced diabetes in albino mice

Objective: Cassia occidentalis (CO) (family: Caesalpiniaceae) is a common weed which is widely used to treat inflammation, hepatotoxicity, antimalarial activities, sore eyes, hematuria, rheumatism, typhoid, asthma, leprosy and diabetes in folklore medicine in India. The present study was carried out to investigate the antidiabetic activity of ethanolic extract of C. occidentalis roots. Methods: Root extract of C. occidentalis (RCO) was administered orally at two doses (250 and 500 mg/kg) to normal and streptozotocin (STZ) induced NIDDM. Fasting blood glucose (FBG) level, biochemical parameters like blood glucose, serum cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides (TG), total protein, urea, creatinine, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) levels and physical parameters like change in body weight, food intake, water intake and levels in liver were performed for the evaluation of hypoglycemic effects. Results: Both the doses of RCO caused a marked decrease in FBG levels in STZ induced type 2 diabetic mice. RCO decreased the blood glucose, food intake, water intake, organ weight, serum cholesterol, TG, creatinine, SGOT and SGPT levels with significant value and increased the levels of HDL cholesterol and total protein with a significant value (P < 0.05–0.01). The decrease in body weight induced by STZ was restored with a significant value (P < 0.01) at both doses. Conclusion: The results suggest that ethanolic roots extract of C. occidentalis Linn. possesses hypoglycemic potential for the NIDDM and support the traditional use of the roots of plant as hypoglycemic agent

Antifertility potential of hydroalcoholic extract of Cordia dichotoma G Forst. leaves: A folklore medicine used by Meena community in Rajasthan state in India

Objective: To assess antifertility activity of hydroalcoholic extract of Cordia dichotoma G Forst. (C. dichotoma) leaves, which are traditionally used to produce sterility among the tribal women through its abortificient activity. Methods: Acute toxicity study was carried out in adult albino rats. The antifertility activity of extract at two dose level (200 and 400 mg/kg, orally) was evaluated in two experimental animal models i.e. anti-implantation and estrogenic/antiestrogenic activity in female rats by observing number of implants, vaginal cornification, body weight, uterus weight and biochemical investigation. Results: The extract was found to be safe up to dose of 2 000 mg/kg body weight when administered orally. A good anti-implantation (81.22%) activity in female rats was observed at the tested dose levels (200 and 400 mg/kg, orally). The extract further showed more significant (P<0.01) increase in uterine weight and significant change in biochemical parameters in immature rats. Simultaneous administration of extract along with ethinyl estradiol showed significant estrogenic activity. Conclusions: The results suggest that hydro alcoholic extract of C. dichotoma leaves possess significant antifertility activity, which is consistent with the literature report in folk medicine of this plant in fertility regulation

Major breakthroughs in the field of biopesticides in recent antiquity

The world's population is rapidly increasing, putting a colossal strain on the world's food supply. Pesticides are one of the most frequent strategies for increasing food production, but their continued usage has some pessimistic consequences for the environment. Over the last two decades, there has been a surge in interest in biopesticides as a prospective replacement. A bibliometric study was conducted from 2002 to 2021 to identify the scientific evolution of biopesticides. In the dimension database, a total of 5680 documents were identified as suitable for this analysis. The documents were analyzed, and nations were ranked based on authors, productivity, article citations, and co-authorship using parameters such as the number of papers, article citations, keywords, source impact, and country of publication. From 2002 to 2021, Pest Management Science and the Journal of Economic Entomology produced the most articles as well as the top contributions in biopesticide publishing by authors Benelli (first) and Tyagi (second). In 2006, Halkier received the highest degree of citation, while Berg received the highest level of citation in 2009. The University of Queensland and the University of Florida were the top two institutes that contributed to the publication of biopesticides

Prevalence of Depression, stress and anxiety symptoms among type 2 diabetics attending life style modification setting - A descriptive cross-sectional study

Introduction: Coexistence of diabetes and depression, stress and anxiety increase the risk of diabetes complications and reduces the overall quality of life. Objectives: To assess the prevalence of depression, stress and anxiety among patients with type 2 diabetes mellitus attending a community-based and peer-led life style modification setting.Materials and methods: Descriptive study was carried out among 145 purposively selected clinically diagnosed type 2 diabetics attending community-based and peer-led life style modification setting from February 2019 to July 2019. Patients were interviewed regarding depression, stress and anxiety using the Patient Health Questionnaire-9 (PHQ- 9) and Generalized Anxiety Disorders-7 (GAD-7) and Cohen’s perceived stress scale (PSS-10). Data were analysed using coGuide software. The level of statistical significance assumed in all the calculations was p&lt;0.05.Results:The mean age was 52.39± 5.79 years with equal proportion of males 73 (50.34%) and females 72 (49.66%). The mean duration of diabetes was 7.41± 6.39 years. The Cohen perceived stress score was low in 27(18.62%),moderate in 101(69.66%) and high in17(11.72%) participants. The GAD-7 anxiety score was mild in 55 (37.93%),moderate in 31 (21.38%)and high in 17(11.72%) participants. The PHQ score was mild in 42(28.97%) and was severe in only 8(5.52%) participants. The association of depression, stress and anxiety was significant only for gender (p -value of 0.006).Conclusion:Prevalence of depression, stress and anxiety was mild to moderate among patients with type 2 diabetes mellitus attending a community-based life style modification settin

Adsorption of C2 gases over CeO2-based catalysts: synergism of cationic sites and anionic vacancies

The synthesis of novel and efficient catalysts for acetylene hydrogenation exhibiting high selectivity towards ethylene is important due to the presence of selective acetylene hydrogenation reaction in petrochemical processing. Since adsorption of C2 gases constitutes the primary step in catalytic hydrogenation and governs the selectivity of the catalysts, we have explored the C2-adsorption potential of reducible CeO2-based systems. The adsorption of C2-gases over CeO2-based materials was assessed using experimental in situ spectroscopic techniques and in silico theoretical studies based on density functional theory. The effect of Pd2+ substitution on adsorption was studied. The addition of Pd2+-ions was found to enhance the adsorption of the gases. Theoretical calculations provided insights into the modes of adsorption, adsorption energetics and reactant–catalyst interactions. The role of the presence of cationic substitution and anionic vacancies in strengthening the adsorption of gases was established. Pd-substituted reduced CeO2 showed activity for the adsorption of all C2 gases. On the basis of the aforementioned experimental and theoretical observations, the catalysts were tested for acetylene hydrogenation, and Pd-substituted CeO2 was found to be a good catalyst for the reaction with complete acetylene conversion observed below 100 °C.by Manjusha C. Padole, Bhanu Pratap Gangwar, Aman Pandey, Aditi Singhal, Sudhanshu Sharma and Parag A. Deshpand