Energy utilization during ovarian development of the cichlid fish Oreochromis mossambicus (Peters) inhabiting a perennial lentic water body in Bangalore, India.

Mozambique tilapia Oreochromis mossambicus (Peters) is an invasive fish and a continuous breeder in inland waters of India. Present investigation highlights the distinct developmental stages of developing ovary and associated changes in the energy content. This investigation helps to understand the allocation of energy for development of eggs, prespawn and also oral brooding by the female. Although it is a continuous breeder, based on size of the ovary, number of eggs, their size and energy content, immature, early maturing, developing, prespawning and spawning stages are clearly noticed. Egg diameter during development of ovary varied between 0.31 mm (immature) and 2.21 mm (spawning). Energy content of ovary from immature to spawning stage ranged from 20.7515 kJ g-1 dry ovary to 31.1560 kJ g-1 dry ovary. Nearly 28.73% of energy content of ovary is expended for spawning. Similarly, yolk-sac fry utilized nearly 25.85% of energy of the fertilized egg for its development. Energy content of ovary of mouth-brooding female averaged 22.9528 kJ g-1 dry ovary, which is comparable to energy content of early maturing stage of ovary (24.5558 kJ g-1 dry ovary). A strong correlation between body weight and energy content of the developing ovary (P < 0.01), and between ovary weight and energy content of ovary (P < 0.01), was evident. During mouth-brooding, the fish continues to allocate energy to its developing ovary. Energy investment by the fish is the result of simultaneous processes associated with gonadal and somatic energy. As body size growth and gonadal development are interconnected, information on energy utilization by an iteroparous mouth-brooding fish could provide the pattern of energy allocation during ovarian developmental phase. Further details of energy utilization, as explained in this paper, could be used as one of the factors to predict the efficiency of fish production.

Genome wide association study of MAGIC population reveals a novel QTL for salinity and sodicity tolerance in rice.

The present study was conducted to identify the novel QTLs controlling salinity and sodicity tolerance using indica MAGIC rice population. Phenotyping was carried out in salinity (EC ~ 10 dS/m) and sodicity (pH ~ 9.8) at the seedling stage. Among 391 lines, 43 and 98 lines were found tolerant and moderately tolerant to salinity. For sodicity condition, 2 and 45 lines were showed tolerance and moderately tolerance at seedling stage. MAGIC population was genotyped with the help of genotyping by sequencing (GBS) and filtered 27041SNPs were used for genome wide marker trait association studies. With respect to salinity tolerance, 25 SNPs were distributed on chromosomes 1, 5, 11 and 12, whereas 18 SNPs were mapped on chromosomes 6, 4 and 11 with LOD value of > 3.25 to sodicity tolerance in rice. The candidate gene analysis detected twelve causal genes including SKC1 gene at Saltol region for salinity and six associated genes for sodic stress tolerance. The significant haplotypes responsible for core histone protein coding gene (LOC_Os12g25120) and three uncharacterized protein coding genes (LOC_Os01g20710, LOC_Os01g20870 and LOC_Os12g22020) were identified under saline stress. Likewise, five significant haplotypes coding for ribose 5-phosphate isomerise (LOC_Os04g24140), aspartyl protease (LOC_Os06g15760), aluminum-activated malate transporter (LOC_Os06g15779), OsFBX421-Fbox domain containing protein (LOC_Os11g32940) and one uncharacterized protein (LOC_Os11g32930) were detected for sodic stress tolerance. The identified novel SNPs could be the potential candidates for functional characterization. These candidate genes aid to further understanding of genetic mechanism on salinity and sodicity stress tolerance in rice. The tolerant line could be used in future breeding programme to enhance the salinity and sodicity tolerance in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01174-8.

Enhancing trehalose biosynthesis improves yield potential in marker-free transgenic rice under drought, saline, and sodic conditions.

Edaphic factors such as salinity, sodicity, and drought adversely affect crop productivity, either alone or in combination. Despite soil sodicity being reported as an increasing problem worldwide, limited efforts have been made to address this issue. In the present study, we aimed to generate rice with tolerance to sodicity in conjunction with tolerance to salinity and drought. Using a fusion gene from E. coli coding for trehalose-6-phosphate synthase/phosphatase (TPSP) under the control of an ABA-inducible promoter, we generated marker-free, high-yielding transgenic rice (in the IR64 background) that can tolerate high pH (~9.9), high EC (~10.0 dS m-1), and severe drought (30-35% soil moisture content). The transgenic plants retained higher relative water content (RWC), chlorophyll content, K+/Na+ ratio, stomatal conductance, and photosynthetic efficiency compared to the wild-type under these stresses. Positive correlations between trehalose overproduction and high-yield parameters were observed under drought, saline, and sodic conditions. Metabolic profiling using GC-MS indicated that overproduction of trehalose in leaves differently modulated other metabolic switches, leading to significant changes in the levels of sugars, amino acids, and organic acids in transgenic plants under control and stress conditions. Our findings reveal a novel potential technological solution to tackle multiple stresses under changing climatic conditions.

Randomised phase III trial of vinflunine plus capecitabine versus capecitabine alone in patients with advanced breast cancer previously treated with an anthracycline and resistant to taxane.

Background: Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II studies in this setting and activity and tolerability when combined with capecitabine. We compared the combination of vinflunine plus capecitabine (VC) with single-agent capecitabine. Patients and methods: Patients with locally recurrent/metastatic BC previously treated or resistant to an anthracycline and resistant to taxane therapy were randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine [825 mg/m2 twice daily (b.i.d.), days 1-14] every 3 weeks (q3w) or single-agent oral capecitabine (1250 mg/m2 b.i.d., days 1-14) q3w. The primary end point was progression-free survival (PFS) assessed by an independent review committee. The study had 90% power to detect a 30% improvement in PFS. Results: Overall, 770 patients were randomised. PFS was significantly longer with VC than with capecitabine alone [hazard ratio, 0.84, 95% confidence interval (CI), 0.71-0.99; log-rank P = 0.043; median 5.6 versus 4.3 months, respectively]. Median overall survival was 13.9 versus 11.7 months with VC versus capecitabine alone, respectively (hazard ratio, 0.98; 95% CI, 0.83-1.15; log-rank P = 0.77). No difference in quality of life was observed between the two treatment arms. The most common adverse events (NCI CTCAE version 3.0) in the combination arm were haematological and gastrointestinal. Grade 4 neutropenia was more frequent with VC (12% versus 1% with capecitabine alone); febrile neutropenia occurred in 2% versus 0.5%, respectively. Hand-foot syndrome was less frequent with VC (grade 3: 4% versus 19% for capecitabine alone). Peripheral neuropathy was uncommon in both arms (grade 3: 1% versus 0.3%). Conclusions: Vinflunine combined with capecitabine demonstrated a modest improvement in PFS and an acceptable safety profile compared with capecitabine alone in patients with anthracycline- and taxane-pretreated locally recurrent/metastatic BC. ClinicalTrials.gov: NCT01095003.

Baseline factors predicting a response to neoadjuvant chemotherapy with implications for non-surgical management of triple-negative breast cancer.

BACKGROUND: Patients with triple-negative breast cancer (TNBC) and a pathological complete response (pCR) after neoadjuvant chemotherapy may be suitable for non-surgical management. The goal of this study was to identify baseline clinicopathological variables that are associated with residual disease, and to evaluate the effect of neoadjuvant chemotherapy on both the invasive and ductal carcinoma in situ (DCIS) components in TNBC. METHODS: Patients with TNBC treated with neoadjuvant chemotherapy followed by surgical resection were identified. Patients with a pCR were compared with those who had residual disease in the breast and/or lymph nodes. Clinicopathological variables were analysed to determine their association with residual disease. RESULTS: Of the 328 patients, 36·9 per cent had no residual disease and 9·1 per cent had residual DCIS only. Patients with residual disease were more likely to have malignant microcalcifications (P = 0·023) and DCIS on the initial core needle biopsy (CNB) (P = 0·030). Variables independently associated with residual disease included: DCIS on CNB (odds ratio (OR) 2·46; P = 0·022), T2 disease (OR 2·40; P = 0·029), N1 status (OR 2·03; P = 0·030) and low Ki-67 (OR 2·41; P = 0·083). Imaging after neoadjuvant chemotherapy had an accuracy of 71·7 (95 per cent c.i. 66·3 to 76·6) per cent and a negative predictive value of 76·9 (60·7 to 88·9) per cent for identifying residual disease in the breast and lymph nodes. Neoadjuvant chemotherapy did not eradicate the DCIS component in 55 per cent of patients. CONCLUSION: The presence of microcalcifications on imaging and DCIS on initial CNB are associated with residual disease after neoadjuvant chemotherapy in TNBC. These variables can aid in identifying patients with TNBC suitable for inclusion in trials evaluating non-surgical management after neoadjuvant chemotherapy.

Participatory evaluation guides the development and selection of farmers' preferred rice varieties for salt- and flood-affected coastal deltas of South and Southeast Asia.

Rice is the staple food and provides livelihood for smallholder farmers in the coastal delta regions of South and Southeast Asia. However, its productivity is often low because of several abiotic stresses including high soil salinity and waterlogging during the wet (monsoon) season and high soil and water salinity during the dry season. Development and dissemination of suitable rice varieties tolerant of these multiple stresses encountered in coastal zones are of prime importance for increasing and stabilizing rice productivity, however adoption of new varieties has been slow in this region. Here we implemented participatory varietal selection (PVS) processes to identify and understand smallholder farmers' criteria for selection and adoption of new rice varieties in coastal zones. New breeding lines together with released rice varieties were evaluated in on-station and on-farm trials (researcher-managed) during the wet and dry seasons of 2008-2014 in the Indian Sundarbans region. Significant correlations between preferences of male and female farmers in most trials indicated that both groups have similar criteria for selection of rice varieties. However, farmers' preference criteria were different from researchers' criteria. Grain yield was important, but not the sole reason for variety selection by farmers. Several other factors also governed preferences and were strikingly different when compared across wet and dry seasons. For the wet season, farmers preferred tall (140-170 cm), long duration (160-170 d), lodging resistant and high yielding rice varieties because these traits are required in lowlands where water stagnates in the field for about four months (July to October). For the dry season, farmers' preferences were for high yielding, salt tolerant, early maturing (115-130 d) varieties with long slender grains and good quality for better market value. Pest and disease resistance was important in both seasons but did not rank high. When farmers ranked the two most preferred varieties, the ranking order was sometimes variable between locations and years, but when the top four varieties that consistently ranked high were considered, the variability was low. This indicates that at least 3-4 of the best-performing entries should be considered in succeeding multi-location and multi-year trials, thereby increasing the chances that the most stable varieties are selected. These findings will help improve breeding programs by providing information on critical traits. Selected varieties through PVS are also more likely to be adopted by farmers and will ensure higher and more stable productivity in the salt- and flood-affected coastal deltas of South and Southeast Asia.

Effect of salinity and use of stress indices of morphological and physiological traits at the seedling stage in rice.

Rice (Oryza sativa L.) is the most important cereal crop and a major staple food for majority of the human populations worldwide. Rice crop is sensitive to salinity. In spite of large number of studies on salinity tolerance of rice, our knowledge on the overall effect of salinity on rice seedling growth is limited. Improvement in salt tolerance of crop plants remains indescribable, largely due to the fact that salinity is a complex trait which affects almost every aspect of the physiology, biochemistry and genomics of plants. The present investigation was conducted to establish the relationship between various morphological, physiological traits and stress indices. A set of 131 rice accessions was evaluated in two levels namely, non-stress (EC ~ 1.2 dS/m) and saline stress (EC ~ 10 dS/m) in hydroponics at seedling stage. Root length and shoot lengths were reduced by 52 and 50%, respectively in saline stress compared to non-stress conditions. There was a significant correlation between various morphological and physiological parameters in non-saline in addition to saline stress as well as non-stress. The effect of the increased Na+ concentration in the medium is detrimental to root length and shoot length as observed by reduction in root length and a concomitant reduction in shoot length. Increased concentration of Na+ led to augmented Na+/K+ ratio with increased stress in the medium and decreased expression of traits. A significant positive correlation (r=0.60) was noticed between stress tolerance index (STI) of root and shoot length. The stress susceptibility index (SSI) for root length was expressed significant positive correlation with SSI for shoot length (r=0.43). SSI for K+ content was registered significant negative correlation with STI for Na+ content (r=-0.43). The three accessions namely, IC 545004, IC 545486 and IC 545215 were found to be the best performers adjudged on the morphological and physiological criteria in saline stress situation. These three rice accessions could be used as a donor parent or for genotypic studies in future breeding programs.

Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival.

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive disease. To date, no molecular feature reliably predicts either the response to chemotherapy (CT) or the survival. Using DNA microarrays, we searched for multigene predictors. PATIENTS AND METHODS: The World IBC Consortium generated whole-genome expression profiles of 137 IBC and 252 non-IBC (nIBC) samples. We searched for transcriptional profiles associated with pathological complete response (pCR) to neoadjuvant anthracycline-based CT and distant metastasis-free survival (DMFS) in respective subsets of 87 and 106 informative IBC samples. Correlations were investigated with predictive and prognostic gene expression signatures published in nIBC (nIBC-GES). Supervised analyses tested genes and activation signatures of 19 biological pathways and 234 transcription factors. RESULTS: Three of five tested prognostic nIBC-GES and the two tested predictive nIBC-GES discriminated between IBC with and without pCR, as well as two interferon activation signatures. We identified a 107-gene signature enriched for immunity-related genes that distinguished between responders and nonresponders in IBC. Its robustness was demonstrated by external validation in three independent sets including two IBC sets and one nIBC set, with independent significant predictive value in IBC and nIBC validation sets in multivariate analysis. We found no robust signature associated with DMFS in patients with IBC, and neither of the tested prognostic GES, nor the molecular subtypes were informative, whereas they were in our nIBC series (220 stage I-III informative samples). CONCLUSION: Despite the relatively small sample size, we show that response to neoadjuvant CT in IBC is, as in nIBC, associated with immunity-related processes, suggesting that similar mechanisms responsible for pCR exist. Analysis of a larger IBC series is warranted regarding the correlation of gene expression profiles and DMFS.

Clinical relevance of cancer stem cells in bone marrow of early breast cancer patients.

BACKGROUND: Cancer stem cells (CSCs) are epithelial tumor cells that express CD44(+)CD24(-/lo). CSCs can be further divided into those that have aldehyde dehydrogenase (ALDH) activity (Aldefluor(+)) and those that do not. We hypothesized that if CSCs are responsible for tumor dissemination, their presence in bone marrow (BM) would be prognostic in early stages of breast cancer (EBC) patients. PATIENTS AND METHODS: BM aspirates were collected at the time of surgery from 108 patients with EBC. BM was analyzed for CSCs and ALDH activity by flow cytometry. Overall survival and disease-free survival (DFS) were calculated from the date of diagnosis and analyzed with Kaplan-Meier survival plots. Cox multivariate proportional hazards model was also carried out. RESULTS: Patients with CSCs in BM had a hazard ratio (HR) of 8.8 for DFS (P = 0.002); patients with Aldefluor(+) CSCs had a HR of 5.9 (P = 0.052) for DFS. All deceased patients (n = 7) had CSCs in BM. In multivariate analysis, the presence of CSCs in BM was a prognostic factor of DFS (HR = 15.8, P = 0.017). CONCLUSIONS: The presence of BM metastasis is correlated with CSCs and these CSCs irrespective of ALDH activity are an independent adverse prognostic factor in EBC patients.

Discrete optimal quadratic AGC based cost functional minimization for interconnected power systems.

The increasing complexity and difficulty of the Automatic generation control (AGC) problem has resulted from the increasing scale of interconnected power networks and changing daily demands. The primary goals of AGC are to control frequency variations at nominal levels and tie-line power variances at planned levels. To effectively deal with AGC control difficulties, this study introduces Discrete Optimal Quadratic Automatic Generation Control (OQAGC). One advantages of this method is the differentiation of quadratic cost function results into linear terms while minimizing control actions and minimizing state deviations. This developed control method leads to a simple and easy discrete control law that can be implemented for both linear and nonlinear systems. For optimizing the controller, this research work utilized an optimum control theorem using Lagrangian multipliers, while the functional minimization technique is used for systematically selecting the state and control weighting matrices in discrete form for N control regions (where N is the number of interconnected power systems). The discrete cost function needs are derived using this technique in terms of area control errors, integral area control errors, and control energy expenditure. Four interconnected power systems were analyzed with/without disturbances and area control errors, each with one thermal, hydro, and gas-generating unit. A two-area multi-source power system with renewable energy in control area 2 is analyzed for the performance of the proposed controller with generation rate constraints (GRCs). The functional minimization technique simplifies and eases the choosing of weighting matrices. Furthermore, the simulation findings suggest that the developed discrete optimum quadratic AGC control-based cost functional minimization approach enhances power system dynamics in terms of stability, steady-state performance, and the closed-loop control system's robustness to input load disturbances. As a result, the newly developed OQAGC approach demonstrates the significance of the discrete LQR controller for N multi-area power systems.

Marker-assisted enhancement of bacterial blight (Xanthomonas oryzae pv. oryzae) resistance in a salt-tolerant rice variety for sustaining rice production of tropical islands.

Introduction: Bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae is a major disease of rice, specially in the tropical regions of the world. Developing rice varieties with host resistance against the disease is the most effective and economical solution for managing the disease. Methods: Pyramiding resistance genes (Xa4, xa5, xa13,and Xa21) in popular rice varieties using marker-assisted backcross breeding (MABB) has been demonstrated as a cost-effective and sustainable approach for establishing durable BB resistance. Here, we report our successful efforts in introgressing four resistance genes (Xa4, xa5, xa13, and Xa21) from IRBB60 to CARI Dhan 5, a popular salt-tolerant variety developed from a somaclonal variant of Pokkali rice, through functional MABB. Results and discussion: Both BB and coastal salinity are among the major challenges for rice production in tropical island and coastal ecosystems. Plants with four, three, and two gene pyramids were generated, which displayed high levels of resistance to the BB pathogen at the BC3F2 stage. Under controlled salinity microplot environments, the line 131-2-175-1223 identified with the presence of three gene pyramid (Xa21+xa13+xa5) displayed notable resistance across locations and years as well as exhibited a salinity tolerance comparable to the recurrent parent, CARI Dhan 5. Among two BB gene combinations (Xa21+xa13), two lines, 17-1-69-334 and 46-3-95-659, demonstrated resistance across locations and years, as well as salt tolerance and grain production comparable to CARI Dhan 5. Besides salinity tolerance, five lines, 17-1-69-179, 46-3-95-655, 131-2-190-1197, 131-2-175-1209, and 131-2-175-1239, exhibited complete resistance to BB disease. Following multilocation testing, potential lines have been identified that can serve as a prospective candidate for producing varieties for the tropical Andaman and Nicobar Islands and other coastal locations, which are prone to BB and coastal salinity stresses.

Comparison of assay methods for detection of circulating tumor cells in metastatic breast cancer: AdnaGen AdnaTest BreastCancer Select/Detect™ versus Veridex CellSearch™ system.

The detection of CTCs prior to and during therapy is an independent and strong prognostic marker, and it is predictive of poor treatment outcome. A major challenge is that different technologies are available for isolation and characterization of CTCs in peripheral blood (PB). We compare the CellSearch system and AdnaTest BreastCancer Select/Detect, to evaluate the extent that these assays differ in their ability to detect CTCs in the PB of MBC patients. CTCs in 7.5 ml of PB were isolated and enumerated using the CellSearch, before new treatment. Two cutoff values of ≥2 and ≥5 CTCs/7.5 ml were used. AdnaTest requires 5 ml of PB to detect gene transcripts of tumor markers (GA733-2, MUC-1, and HER2) by RT-PCR. AdnaTest was scored positive if ≥1 of the transcript PCR products for the 3 markers were detected at a concentration ≥0.15 ng/µl. A total of 55 MBC patients were enrolled. 26 (47%) patients were positive for CTCs by the CellSearch (≥2 cutoff), while 20 (36%) were positive (≥5 cutoff). AdnaTest was positive in 29 (53%) with the individual markers being positive in 18% (GA733-2), 44% (MUC-1), and 35% (HER2). Overall positive agreement was 73% for CTC≥2 and 69% for CTC≥5. These preliminary data suggest that the AdnaTest has equivalent sensitivity to that of the CellSearch system in detecting 2 or more CTCs. While there is concordance between these 2 methods, the AdnaTest complements the CellSearch system by improving the overall CTC detection rate and permitting the assessment of genomic markers in CTCs.

Photon emission enhancement studies from the interaction of ultraintense laser pulses with shaped targets.

We study the photon emission by bremsstrahlung and nonlinear Compton scattering from interaction of ultra-intense laser pulses with cone target and flat foil using particle-in-cell simulations. The simulations are performed for laser pulses interacting with Al and Au targets. The strength of the two mechanisms of photon emission from bremsstrahlung and nonlinear Compton scattering are compared. When an ultra-intense (I>10^{22}W/cm^{2}) laser interacts with a cone and a foil target, photon emission by bremsstrahlung is found to be comparable to that from nonlinear Compton scattering. The obtained electron energy as well as the energy and number of photons emitted were found to be higher in case of cone shaped target compared with that of a foil target. The enhanced photon emission from cone shaped target is attributed to the guiding or collimation of hot electrons towards the cone tip from the self-generated magnetic field and electrostatic field along the cone surface which pushes the hot electrons towards the tip.

International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment.

BACKGROUND: Inflammatory breast cancer (IBC) represents the most aggressive presentation of breast cancer. Women diagnosed with IBC typically have a poorer prognosis compared with those diagnosed with non-IBC tumors. Recommendations and guidelines published to date on the diagnosis, management, and follow-up of women with breast cancer have focused primarily on non-IBC tumors. Establishing a minimum standard for clinical diagnosis and treatment of IBC is needed. METHODS: Recognizing IBC to be a distinct entity, a group of international experts met in December 2008 at the First International Conference on Inflammatory Breast Cancer to develop guidelines for the management of IBC. RESULTS: The panel of leading IBC experts formed a consensus on the minimum requirements to accurately diagnose IBC, supported by pathological confirmation. In addition, the panel emphasized a multimodality approach of systemic chemotherapy, surgery, and radiation therapy. CONCLUSIONS: The goal of these guidelines, based on an expert consensus after careful review of published data, is to help the clinical diagnosis of this rare disease and to standardize management of IBC among treating physicians in both the academic and community settings.

Combined effects of malathion and nitrate on early growth, abnormalities, and mortality of wood frog (Rana sylvatica) tadpoles.

Use of pesticides and other agro-chemicals adversely influence amphibians either directly by killing them or by inducing sublethal, chronic effects. Many studies have investigated the effect of mixtures of pesticides or fertilizers. We studied the combined effects of nitrate and malathion ([(dimethoxy phosphino thioyl] butanediotae) on the early growth, expression of abnormalities, and mortality of Wood Frog (Rana sylvatica) tadpoles in a laboratory experiment. Tadpoles were treated with factorial combinations of 0, 8, and 16 mg NO(3)-N l(-1) and 0, 250, 500, and 1,000 µg malathion l(-1) for a period of 14 days. Feeding behaviour, total length, mean tadpole mass, frequencies of abnormalities, and survivorship in each treatment were recorded. Malathion showed a significant negative influence on all parameters and strongly influenced the frequencies of morphological anomalies. In contrast, nitrate alone did not produce any significant effects on behavior, total length, tadpole mass, or the frequency of abnormalities during the experiment. Malathion and nitrate had an interactive effect on tadpole length and mass, but did not affect any other parameters. Our results suggest that exposure to malathion, even at relatively low concentrations can have serious negative consequences for Wood Frog tadpoles. In addition, our results also indicate that there was little synergistic interaction between malathion and nitrate exposure under laboratory conditions.

Differential effects of malathion and nitrate exposure on American Toad and Wood Frog tadpoles.

Organisms living in aquatic ecosystems are increasingly likely to be exposed to multiple pollutants at the same time due to the simultaneous use of several pesticides and fertilizers. We examined the single and interactive effects of environmentally realistic concentrations of nitrate and malathion on two species of tadpoles common in agricultural regions of the United States-the American Toad (Bufo americanus) and the Wood Frog (Rana sylvatica)-using a fully factorial mesocosm experiment that crossed four concentrations of malathion ranging from 0 to 1000 µg/l and two concentrations of nitrate (0 or 8 mg/l). In both B. americanus and R. sylvatica, malathion delayed metamorphosis compared to controls, even at the lowest concentration of malathion. Malathion did not affect survivorship in either species. B. americanus metamorphs were smaller in malathion treatments, whereas R. sylvatica were larger in malathion treatments. Nitrate did not affect survivorship or metamorph size in either species, but did accelerate time to metamorphosis in R. sylvatica. The interaction between nitrate and malathion had no effects in B. americanus and had no effect on R. sylvatica survivorship or metamorph size. However, in the 250 µg/l and 500 µg/l malathion treatments, nitrate reduced the negative effect of malathion on time to metamorphosis in R. sylvatica such that there was little if any delay in metamorphosis compared to the controls in these treatment combinations. This observation suggests that the presence of nitrate might ameliorate the effects of malathion on R. sylvatica. Our results suggest that malathion could have significant effects on anuran populations and communities and that nitrate might potentially mediate such effects in some species.

Effect of Preoperative Biliary Stenting on Outcomes of Pancreaticoduodenectomy.

Biliary drainage before pancreaticoduodenectomy was introduced to decrease morbidity from obstructive jaundice. Recent retrospective and randomised data show that preoperative biliary drainage (PBD) increases perioperative infectious complications. Most patients presenting to our tertiary care centre have undergone drainage procedures prior to surgical consultation. We analysed the impact of PBD, specifically endoscopic stent placement, on the postoperative outcome of pancreaticoduodenectomy at our centre. A cohort of 87 patients undergoing pancreaticoduodenectomy from 2012 to 2016 was identified. Data was collected retrospectively and a comparative analysis of stented and nonstented patients was done. Comparison of the 23 stented patients was done with 23 nonstented patients after matching them for age, sex and bilirubin levels. Median total bilirubin level in stented patients was 10.2 mg/dl versus 7.7 mg/dl in nonstented patients. The infectious complication rate in the stented group was 39.1% versus 12.7% in the nonstented group (P value < 0.05). There was no difference in the anastomotic leak rate between the two groups. Time to curative surgery in the stented group was significantly more than in the nonstented group. Stented patients are at a higher risk for postoperative infectious complications. Patients with obstructive jaundice awaiting surgery should undergo selective biliary drainage after careful planning and discussion between the operating surgeon and the endoscopist.

A dose range finding study of novel oral insulin (IN-105) under fed conditions in type 2 diabetes mellitus subjects.

AIM: The objective of the study was to establish the dose response of IN-105 tablets and explore a possible therapeutic window in type 2 diabetes subjects poorly controlled on metformin. METHODS: The primary objective was to examine the effect of sequential single ascending doses of IN-105 on the plasma glucose concentration under fed conditions. All subjects received, sequentially, matching placebo, 10, 15, 20 and 30 mg IN-105 tablets in five consecutive periods. Tablets were administered 20 min prior to meal in all the periods. Plasma levels of immunoreactive insulin, C-peptide and glucose were measured up to 180 min from the time of dosing. The changes in postprandial glucose levels at 120 min in response to IN-105 administration were also compared against those of placebo. RESULTS: Changes in glucose from baseline (mean +/- s.d.) at 140 min (2 h postprandial) were 94.84 +/- 22.3, 79.45 +/- 43.00, 70.68 +/- 35.71, 63.47 +/- 42.75 and 53.06 +/- 47.27 mg/dL, respectively, and exhibited linear dose-response. The insulin C(max) values were found to be 50.8 +/- 26.0 mU/L for placebo, 100.3 +/- 66.7 with 10 mg IN-105, 177.69 +/- 150.3 with 15 mg IN-105, 246.2 +/- 245.2 with 20 mg IN-105 and 352.5 +/- 279.3 mU/L with 30 mg of IN-105. CONCLUSIONS: IN-105 absorption is proportional to the dose administered. The 2-h postprandial glucose excursion was reduced in a dose proportional manner. Circulating C-peptide levels were found to be suppressed in proportion to the IN-105 exposure. IN-105 reduces glucose excursion despite lower endogenous insulin secretion. IN-105 seems to have a wide therapeutic window as no clinical hypoglycaemia was observed at any of the doses studied.

Introgressed Saltol QTL Lines Improves the Salinity Tolerance in Rice at Seedling Stage.

Rice is a staple food crop in Asia and plays a crucial role in the economy of this region. However, production of rice and its cultivating areas are under constant threat of soil salinity. A major QTL, Saltol, responsible for salinity tolerance at seedling stage has been mapped on chromosome 1 using Pokkali/IR29 Recombinant Inbred Lines (RIL) population. The present study was aimed to incorporate Saltol Quantitative Trait Loci (QTL) in two high yielding mega rice varieties i.e. Pusa44 and Sarjoo52 through Marker Assisted Backcross Breeding (MABB). To improve the seedling stage salinity tolerance in these cultivars, we introgressed the Saltol QTL from donor parent FL478 a derivative of Pokkali. A total of three backcrosses (BC3) followed by selfing have led to successful introgression of Saltol QTL. Foreground selection at each breeding cycle was done using micro-satellite markers RM3412 and AP3206 to confirm Saltol QTL. The precise transfer of Saltol region was established using recombinant selection through flanking markers RM493 and G11a. Finally, 10 Saltol near isogenic lines (NILs) of Pusa44 and eight NILs of Sarjoo52 were successfully developed. These NILs (BC3F4) were evaluated for seedling stage salinity under hydroponic system. The NILs PU99, PU176, PU200, PU215, PU229, PU240, PU241, PU244, PU252, PU263 of Pusa44 and SAR17, SAR23, SAR35, SAR39, SAR77, SAR87, SAR123, SAR136 NILs of Sarjoo52 confirmed tolerance to salinity with low salt injury score of 3 or 5. Ratio of Na+/K+ content of Saltol NILs ranged from 1.26 to 1.85 in Pusa44 and 1.08 to 1.69 in Sarjoo52. The successfully developed NILs were further phenotyped stringently for morphological traits to estimate Phenotypic Recovery. Background selection of NILs along with parents was carried out with 50K SNP chip and recovered 94.83-98.38% in Pusa44 NILs and 94.51 to 98.31% in Sarjoo52 NILs of recurrent genome. The present study of MAB has accelerated the development of salt tolerant lines in the genetic background of Pusa44 and Sarjoo52. These NILs could be used for commercial cultivation in saline affected area.