Effect of Serine on Growth and Biochemical Constituents of Zea mays L., Triticum aestivum L., and Abelmoschus esculentus L. under Arsenic Toxicity

Background: Various human activities, such as industrialization, modern farming methods, and mining increase the concentration of heavy metals in air, water and soil. Heavy metal poisoning of soil results in a number of environmental issues and has deleterious effects on both plants and animals. Therefore, the purpose of this study was to investigate the effects of Arsenite (As) and As+ Serine (Ser) on growth and biochemical components in the early growth stages of Abelmoschus esculentus (L.) Moench, Triticum aestivum L., and Zea mays L. (selected crops).Methods: Pot experiments were carried out at completely random manner, with 10-12 seeds grown in each pot with three replicates. Seeds and seedlings in pots treated with different concentrations of As and As+Ser. After a 21-days of germination period, we gathered the growth-related parameters (root number, root length, shoot length, and leaf number) and conducted a biochemical analysis.Results: The growth of selected plants was adversely impacted by Arsenic stress, whereas the detrimental impact was minimal after treatments with Serine. Compression of the selected crops showed that Abelmoschus esculentus L. had the most detrimental impact on agronomic parameters. Biochemical constituents such Chlorophyll “a” “b”, Total-chlorophyll (Photosynthetic pigments), protein and carotenoid contents formation were reduced at individual treatments of As (25, 50, 75 and 100pmm) compared to As+Ser and control treatment, while the proline contents were increased considerably at treatment 100 ppm (As) of the selected crops.Conclusion: The results showed that As had a greater negative impact on growth and biochemical constituents, whereas Ser had a reduced adverse impact on selected crops. Abelmoschus esculentusL. had a higher sensitivity compared to other selected crops

Advances in stable and flexible perovskite solar cells

Roll-to-roll (R2R) production is an innovative approach and is fast becoming a very popular industrial method for high throughput and mass production of solar cells. Replacement of costly indium tin oxide (ITO), which conventionally has served as the transparent electrode would be a great approach for roll to roll production of flexible cost effective solar cells. Indium tin oxide (ITO) and fluorine-doped tin oxide (FTO) are brittle and ultimately limit the device flexibility. Perovskite solar cells (PSCs) have been the centre of photovoltaic research community during the recent years owing to its exceptional performance and economical prices. The best reported PSCs fabricated by employing mesoporous TiO2 layers require elevated temperatures in the range of 400–500 °C which limits its applications to solely glass substrates. In such a scenario developing flexible PSCs technology can be considered a suitable and exciting arena from the application point of view, them being flexible, lightweight, portable, and easy to integrate over both small, large and curved surfaces

Time trends in the incidence of cancer cervix in Karachi South, 1995-2002

Introduction:The objective of the study was to determine the trends of cancer cervix in Karachi South during an eight (1995-2002) year period. Methododology: Cancer cervix cases recorded at Karachi Cancer Registry during 1st January 1995 to 31st December 2002 were analyzed. Trends were studied by analyzing the age standardized incidence rates (ASR)s in 2 time periods, 1995-97 and 1998-2002. Results: Cancer cervix ranked sixth in the 1995-97 period the age standardized incidence rate (ASR) world and crude incidence rate (CIR) per 100,000 were 6.81 and 3.22. It reached the fifth ranking in the 1998-2002 period with an ASR and CIR of 7.5 and 4.0 per 100,000. Thus between 1995 and 2002, the incidence of cervical cancer registered an approximate 10% increase. The mean age of the cancer cases was 53.3 years (SD 11.6, 95% CI 50.58, 55.96, range 32-85 years) and 50.7 years (SD 11.7, 95% CI 48.8, 52.5, range 51 years) in period 1 and 2 respectively. The morphological components of squamous cell carcinoma and adenocarcinoma remained stable during this period, though a marginally higher component and increasing incidence of adenocarcinoma was observed throughout. A negligible down staging was observed in the 1998-2002 period. Localized malignancy was observed in 30.8% in period 2 as compared to 25.7% in period 1 and the component of carcinoma in situ increased from 0% percent in period 1 to 1.3% in the second period. Despite this two thirds of the cases still presented with a regional or distant spread of disease. Conclusion: Pakistan at present falls into a low risk cancer cervix region. The cause of concern is the steadily increasing incidence especially in the younger birth cohorts, the advanced disease at presentation, insignificant in-situ cancers and no preventive intervention or awareness practices in place

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

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

Genomic profile of a patient with triple negative essential thrombocythemia, unresponsive to therapy: A case report and literature review

Clonal analysis of patients with triple negative myeloproliferative neoplasm (MPN) has provided evidence of additional aberrations, including epigenetic alterations. To discover such novel genetic aberrations, patients were screened through next-generation sequencing using a myeloid sequencing panel of 54 genes using a genetic analyser. Genetic variants in 28 genes, including TET2, BCOR, BCR, and ABL1 were identified in a triple negative essential thrombocythemia (ET) patient. The individual role of some of these variants in disease pathogenesis has yet to be studied. Somatic mutations in the same genes have been reported with variable frequencies in myeloid malignancies. However, no pathogenic impact of these variants could be found; therefore, long-term follow up of patients with genetic analysis of a large cohort and the use of whole genome sequencing is required to assess the effects of these variants

Increasing incidence of non-Hodgkin\u27s lymphoma in Karachi, 1995-2002

This first population-based study of non- Hodgkin lymphoma (NHL) from any region in Pakistan, provides an overview of the incidence pattern and time trends in Karachi and generates hypotheses for future experimental research. Epidemiological data for 429 incident (1(st) Jan 1995 to 31(st) Dec 2002), microscopically verified nodal and extra-nodal NHL cases, registered at the Karachi Cancer Registry (KCR) for Karachi South, were reviewed. The age standardized incidence rate (ASIR) was 5.3/100,000 in males (M) and 4.1/100,000 in females (F), in 1995. A gradual increase in the annual incidence was observed during the study period, with NHL incidence rate increasing in 2002 to 8.4/100,000 in men and 6.5/100,000 in women, almost double the 1995 rates. NHL affected all age groups in both genders and for each group the ASIR was higher among men than women, with an overall gender ratio of 1.9. The mean ages of the patients were 41.5 years (95% CI 39.1; 43.8) in males and 44.0 years (95% CI 40.8; 47.1) in females. The adult to childhood ratios were 8.6 (M) and 10.7 (F). B-cell NHL comprised 81.0% of NHL in males and 87.3% in females. One fourth of the NHL cases were extra-nodal, the largest group was of gastrointestinal origin (54.1% M, 38.5% F). The gastric component was 21% M and 25.6% F. Odds Ratios for sex, age-groups, ethnicity, religion, and subdivision by socio-economic categories were calculated by considering all malignancies, except lymphoproliferative disorders as controls. The odds ratio (OR) in men was 2.2 (95% CI 0.6; 3.0). Children and adolescents were at the highest risk of developing NHL, especially the 5-9 year olds, in both genders. A marginally higher risk was observed for the lower socioeconomic categories and for ethnicities belonging to Northern and North Western Pakistan (Punjabi, Pushtu and Baluch) residing in Karachi South. The incidence rates of NHL registered in Karachi South are likely to be a reflection of non-AIDS-associated NHL. Estimated HIV/AIDS incidence was too low during the study period in this population to have an impact on NHL incidence. The preponderance of low and intermediate grade lymphomas, paucity of central nervous system NHL and a higher childhood NHL component support this hypothesis. As yet unpublished reports, however, are raising the alarm on rising HIV positivity. NHL correlation with HIV/AIDS status and studies identifying risk factors of non- HIV/AIDS associated NHL (childhood viral infections, Hepatitis C virus, and Helicobacter pylori) are potential areas for future experimental and epidemiological research