Genetic Diversity and Population Structure of Maize (Zea mays L.) Inbred Lines in Association with Phenotypic and Grain Qualitative Traits Using SSR Genotyping.

Maize (Zea mays L.) is an important cereal and is affected by climate change. Therefore, the production of climate-smart maize is urgently needed by preserving diverse genetic backgrounds through the exploration of their genetic diversity. To achieve this, 96 maize inbred lines were used to screen for phenotypic yield-associated traits and grain quality parameters. These traits were studied across two different environments (Anand and Godhra) and polymorphic simple sequence repeat (SSR) markers were employed to investigate the genetic diversity, population structure, and trait-linked association. Genotype-environment interaction (GEI) reveals that most of the phenotypic traits were governed by the genotype itself across the environments, except for plant and ear height, which largely interact with the environment. The genotypic correlation was found to be positive and significant among protein, lysine and tryptophan content. Similarly, yield-attributing traits like ear girth, kernel rows ear-1, kernels row-1 and number of kernels ear-1 were strongly correlated to each other. Pair-wise genetic distance ranged from 0.0983 (1820194/T1 and 1820192/4-20) to 0.7377 (IGI-1101 and 1820168/T1). The SSRs can discriminate the maize population into three distinct groups and shortlisted two genotypes (IGI-1101 and 1820168/T1) as highly diverse lines. Out of the studied 136 SSRs, 61 were polymorphic to amplify a total of 131 alleles (2-3 per loci) with 0.46 average gene diversity. The Polymorphism Information Content (PIC) ranged from 0.24 (umc1578) to 0.58 (umc2252). Similarly, population structure analysis revealed three distinct groups with 19.79% admixture among the genotypes. Genome-wide scanning through a mixed linear model identifies the stable association of the markers umc2038, umc2050 and umc2296 with protein, umc2296 and umc2252 with tryptophan, and umc1535 and umc1303 with total soluble sugar. The obtained maize lines and SSRs can be utilized in future maize breeding programs in relation to other trait characterizations, developments, and subsequent molecular breeding performances for trait introgression into elite genotypes.

Genetic gains with rapid-cycle genomic selection for combined drought and waterlogging tolerance in tropical maize (Zea mays L.).

Rapid cycle genomic selection (RC-GS) helps to shorten the breeding cycle and reduce the costs of phenotyping, thereby increasing genetic gains in terms of both cost and time. We implemented RC-GS on two multi-parent yellow synthetic (MYS) populations constituted by intermating ten elite lines involved in each population, including four each of drought and waterlogging tolerant donors and two commercial lines, with proven commercial value. Cycle 1 (C1 ) was constituted based on phenotypic selection and intermating of the top 5% of 500 S2 families derived from each MYS population, test-crossed and evaluated across moisture regimes. C1 was advanced to the next two cycles (C2 and C3 ) by intermating the top 5% selected individuals with high genomic estimated breeding values (GEBVs) for grain yield under drought and waterlogging stress. To estimate genetic gains, population bulks from each cycle were test-crossed and evaluated across locations under different moisture regimes. Results indicated that the realised genetic gain under drought stress was 0.110 t ha-1 yr-1 and 0.135 t ha-1 yr-1 , respectively, for MYS-1 and MYS-2. The gain was less under waterlogging stress, where MYS-1 showed 0.038 t ha-1 yr-1 and MYS-2 reached 0.113 t ha-1 yr-1 . Genomic selection for drought and waterlogging tolerance resulted in no yield penalty under optimal moisture conditions. The genetic diversity of the two populations did not change significantly after two cycles of GS, suggesting that RC-GS can be an effective breeding strategy to achieve high genetic gains without losing genetic diversity.

Post Chikungunya Chronic Arthritis: Systemic Inflammatory Status Triggering Acute Coronary Syndrome.

BACKGROUND: Atherosclerosis, inflammation and coronary plaque destabilization are linked to each other. Infections due to various microbes may trigger Acute Coronary Syndrome (ACS) by systemic inflammation cascade. METHODS: We have evaluated the prevalence of Post Chikungunya Chronic Arthritis (PCCA) among 400 consecutive ACS patients (Case group) and compared with control group subjected to elective surgery by the prospective case-control observational study. Cases were excluded if standard criteria of ACS were not satisfied and in the control group if the patient suffered a Myocardial Infarction (MI) within 28 days of elective surgery. PCCA duration more than two years or serum IgM anti-CCP positive patients were also excluded from the case as well as a control group. RESULTS: The case and control groups were similar except, less number of heart failure (O.R.7.3, 95% C.I. 3.3-15.9) and chronic kidney injury patients (O.R. 0.5, 95% C.I. 0.3-0.9) in the elective surgery (control) group. PCCA was present in 24 out of 400 ACS cases and 8 out of 400 control group. Among ACS case-patients, those suffering from PCCA tended to be younger and more often women, with more diabetes, hypertension, chronic kidney injury and high mean CRP. In unadjusted analysis PCCA was three times more common in the case versus control (O.R. 3.0, 95% C.I. 1.4- 6.4); results were indistinguishable after multidiscipline adjustment (O.R. 3.0, 95% C.I. 1.3-6.8). CONCLUSION: PCCA is common among patients with ACS and post-infective systemic inflammation of PCCA may trigger plaque destabilization.

Comparative effectiveness and safety of nab-paclitaxel plus carboplatin vs gemcitabine plus carboplatin in first-line treatment of advanced squamous cell non-small cell lung cancer in a US community oncology setting.

INTRODUCTION: Real-world comparative effectiveness, safety, and supportive care use of nab-paclitaxel plus carboplatin vs gemcitabine plus platinum were analyzed in patients with advanced or metastatic squamous cell non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients who received ≥ 1 cycle of first-line nab-paclitaxel plus carboplatin or gemcitabine plus platinum were identified from the Navigating Cancer database. Clinical effectiveness endpoints included overall survival (OS) and time to treatment discontinuation (TTD). Other endpoints included safety and utilization of supportive care. Cox proportional hazards models were used to control for potential confounding effects of baseline characteristics. RESULTS: In total, 193 patients were included (nab-paclitaxel plus carboplatin, n = 61; gemcitabine plus platinum, n = 132). Baseline characteristics were generally similar between the cohorts. Patients receiving nab-paclitaxel plus carboplatin had a significantly longer OS than those receiving gemcitabine plus carboplatin (median, 12.8 vs 9.0 months; P = 0.03). However, the adjusted difference was not statistically significant (adjusted HR 1.55; 95% CI, 0.99-2.42; P = 0.06). nab-Paclitaxel plus carboplatin-treated patients had significantly longer TTD than gemcitabine plus carboplatin-treated patients (median, 4.3 vs 3.5 months; P = 0.03; adjusted HR 1.39; 95% CI, 1.01-1.90; P = 0.04). Grade 3 or 4 anemia and neutropenia were significantly lower in patients treated with nab-paclitaxel plus carboplatin vs gemcitabine plus carboplatin. Nausea and neuropathy (grade not specified) were significantly higher in the nab-paclitaxel plus carboplatin than the gemcitabine plus carboplatin group. No differences in supportive care use were observed between the cohorts. CONCLUSION: These real-world data support the effectiveness and safety of nab-paclitaxel plus carboplatin for first-line treatment of advanced squamous cell NSCLC.

Comparative effectiveness and resource utilization of nab-paclitaxel plus gemcitabine vs FOLFIRINOX or gemcitabine for the first-line treatment of metastatic pancreatic adenocarcinoma in a US community setting.

INTRODUCTION: Despite a clinically relevant, statistically significant survival benefit with nab-paclitaxel plus gemcitabine and FOLFIRINOX vs single-agent gemcitabine for metastatic pancreatic cancer (mPC), little is known regarding their real-world effectiveness. We analyzed patients with mPC using a nationally representative electronic medical records database to address this unmet need. METHODS: This retrospective analysis of the Navigating Cancer database compared outcomes among patients who received first-line nab-paclitaxel plus gemcitabine, FOLFIRINOX, or gemcitabine for mPC. Effectiveness, safety, and supportive care use were examined. nab-Paclitaxel plus gemcitabine was the reference for statistical comparisons. RESULTS: Baseline characteristics were similar except age (oldest patients were in the gemcitabine cohort followed by nab-paclitaxel plus gemcitabine, then FOLFIRINOX). Patients receiving nab-paclitaxel plus gemcitabine (n=122) demonstrated similar time to treatment discontinuation (TTD; median, 3.4 vs 3.8 months; P=0.947) and database persistence (DP; median, 8.6 vs 8.6 months; P=0.534) vs FOLFIRINOX (n=80); however, TTD (median, 3.4 vs 2.2 months; P<0.001) and DP (median, 8.6 vs 5.3 months; P=0.030) were significantly longer with nab-paclitaxel plus gemcitabine vs gemcitabine (n=46). There were more any-grade adverse events with FOLFIRINOX or gemcitabine vs nab-paclitaxel plus gemcitabine (95% or 89% vs 84%, respectively). CONCLUSION: This real-world analysis confirms the phase III MPACT trial findings and demonstrates that nab-paclitaxel plus gemcitabine has effectiveness similar to that of FOLFIRINOX but greater tolerability for treating mPC despite younger patients being in the FOLFIRINOX cohort. These findings support nab-paclitaxel plus gemcitabine as an appropriate first-line treatment option for patients with mPC.

Comparative Effectiveness and Resource Usage in Patients Receiving First-line Taxane-based Chemotherapy for Stage IV Non-Small-cell Lung Cancer in a US Community Oncology Setting.

BACKGROUND: Weekly (qw) nanoparticle albumin-bound (nab)-paclitaxel was approved for advanced non-small-cell lung cancer based on the results from a phase III trial in which nab-paclitaxel/carboplatin demonstrated a significantly greater response rate compared with paclitaxel/carboplatin every 3 weeks (q3w). Little information exists on relative real-world results. MATERIALS AND METHODS: The present retrospective study used data from a national electronic medical record database. Patients receiving first-line nab-paclitaxel qw, paclitaxel qw, or paclitaxel q3w for stage IV non-small-cell lung cancer (NSCLC) were identified. The total cumulative dose, time to treatment discontinuation (TTD), and database persistence (a proxy measure for survival) were analyzed for all patients and for the squamous and elderly subgroups. RESULTS: A total of 114, 208, and 153 patients received nab-paclitaxel qw, paclitaxel qw, and paclitaxel q3w, respectively. In the corresponding treatment arms, the median age was 72, 69, and 67 years; 56%, 48%, and 37% were aged ≥ 70 years; and 75%, 43%, and 23% had squamous cell NSCLC. The total cumulative dose was significantly greater with nab-paclitaxel qw. The TTD was longer with nab-paclitaxel qw than with paclitaxel qw (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.40-0.72; P < .001) or with paclitaxel q3w (HR, 0.53; 95% CI, 0.38-0.73; P < .001). Database persistence was longer with nab-paclitaxel qw than with paclitaxel qw (HR, 0.56; 95% CI, 0.39-0.79; P = .001) or with paclitaxel q3w (HR, 0.52; 95% CI, 0.34-0.78; P = .002). The TTD after experiencing any hematologic adverse event was longer with nab-paclitaxel qw. The findings were consistent across the subgroup analyses. CONCLUSION: In a real-world setting, nab-paclitaxel qw was associated with a significantly greater cumulative dose and significantly longer TTD and database persistence compared with paclitaxel qw and paclitaxel q3w.

Comparison of treatment patterns, resource utilization, and cost of care in patients with metastatic pancreatic cancer treated with first-line nab-paclitaxel plus gemcitabine or FOLFIRINOX.

BACKGROUND: We compared real-world treatment patterns, resource utilization, and cost of care for patients with metastatic pancreatic cancer treated with first-line nab-paclitaxel + gemcitabine or FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin). METHODS: This was a retrospective study of inpatient and hospital-based outpatient data in the United States. Primary endpoints included median time to treatment discontinuation (TTD) and total cost of care per patient per month. Secondary endpoints included supportive care costs and hospitalization rate and length. RESULTS: Overall, 345 patients were included (nab-paclitaxel + gemcitabine, n = 182; FOLFIRINOX, n = 163). Median TTD was significantly longer with nab-paclitaxel + gemcitabine vs FOLFIRINOX (4.3 vs 2.8 months; P = .0009). Mean acquisition cost was higher with nab-paclitaxel + gemcitabine ($10,643 vs $6549; P = .0043), but mean total cost of care was lower ($16,628 vs $19,936; P = .1740). Supportive care cost was significantly lower with nab-paclitaxel + gemcitabine ($1995 vs $6456; P < .0001). Hospitalization rate and length were both significantly lower with nab-paclitaxel + gemcitabine. CONCLUSIONS: Despite higher acquisition costs with nab-paclitaxel + gemcitabine, FOLFIRINOX-treated patients had higher total costs driven by supportive care. Toxicity-related costs and drug acquisition costs should be considered when evaluating total cost of care.

Effects of ethanol extract of Ficus bengalensis (bark) on inflammatory bowel disease.

OBJECTIVE: The present study was designed to evaluate the effects of ethanol extract of Ficus bengalensis Linn. bark (AEFB) on inflammatory bowel disease (IBD). MATERIALS AND METHODS: Effects of AEFB were studied on 2,4,6-trinitrobenzenesulfonic acid (TNBS, 0.25 ml 120 mg/ml in 50% ethanol intrarectally, on first day only) induced IBD in rats. The effects of co-administration of prednisolone (2 mg/kg) and AEFB (250, 500 mg/kg) for 21 days were evaluated. Animals sacrificed at end of the experiment and various histopathological parameters like colon mucosal damage index (CMDI) and disease activity index (DAI) were assessed. In the colon homogenate malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and nitric oxide (NO) levels and in mesentery % mast cell protection was also measured. RESULTS: Rats treated with only TNBS showed more score of CMDI and DAI, higher MDA, NO, MPO, and lower SOD activity as compared to the control group. Treatment with AEFB significantly declined both indices scores and decreased the MPO, MDA, NO, and increased the SOD activity. AEFB also increased the % mast cell protection compared to alone TNBS-treated animals. CONCLUSION: In our study, we found that AEFB has a significant protective effect in the IBD in rats that is comparable to that of prednisolone and may be because of the presence of flavonoids, terpenoids, and phenolic compounds.