Feto-maternal outcome in twin pregnancy

Background: Natural higher orders multiple conceptions are uncommon. The reported incidence ranges from 0.01% to 0.07% of all pregnancies. Multiple births are much more common today than they were in the past. Throughout the world, the prevalence of twin births varies from approximately 2-20 /1000 birth. Overall complications occur in approximately 83% of twin pregnancies as compared to 25% in singleton pregnancies. This delayed childbearing has resulted in an increased maternal age at conception.Methods: Present study is a randomized prospective study of 100 cases of twin pregnancies admitted at our institute from July, 2009 to October, 2011 including all emergency as well as registered cases. . Patients included in this study were from various socio-economic classes and they were having a different level of education. In all cases a detailed history was taken, all routine and specific investigations were done.Results: In this prospective study we observed 100 cases of twin pregnancies. In this study most of the patients (46%) delivered at 33- 36 weeks of gestation. 5%of patients had abortion at an early gestation. Majority of the patients delivered vaginally (61%), followed by LSCS (Lower Segment Caesarean Section) (38%). In this study low birth weight babies were the most common (188 babies) to the extent of 94%. We had 11% (22) extremely low birth weight babies. There were 13 neonatal deaths (6.5%). We observed the highest incidence of twins in the age group of 20 -29 years. The least were below the age of 20 years. The incidence among primigravida and multigravida was almost the same.Conclusions: Most of the complications in multiple gestations are preventable. High risk units in the obstetric ward and well developed NICU set up would reduce the maternal, perinatal morbidity and mortality

Diabetes mellitus and smoking among tuberculosis patients in a tertiary care centre in Karnataka, India

Supported by the TB Union/MSF Course on Operational Researc

Large-scale development of cost-effective SNP marker assays for diversity assessment and genetic mapping in chickpea and comparative mapping in legumes

A set of 2486 single nucleotide polymorphisms (SNPs) were compiled in chickpea using four approaches, namely (i) Solexa/Illumina sequencing (1409), (ii) amplicon sequencing of tentative orthologous genes (TOGs) (604), (iii) mining of expressed sequence tags (ESTs) (286) and (iv) sequencing of candidate genes (187). Conversion of these SNPs to the cost-effective and flexible throughput Competitive Allele Specific PCR (KASPar) assays generated successful assays for 2005 SNPs. These marker assays have been designated as Chickpea KASPar Assay Markers (CKAMs). Screening of 70 genotypes including 58 diverse chickpea accessions and 12 BC3F2 lines showed 1341 CKAMs as being polymorphic. Genetic analysis of these data clustered chickpea accessions based on geographical origin. Genotyping data generated for 671 CKAMs on the reference mapping population (Cicer arietinum ICC 4958 × Cicer reticulatum PI 489777) were compiled with 317 unpublished TOG-SNPs and 396 published markers for developing the genetic map. As a result, a second-generation genetic map comprising 1328 marker loci including novel 625 CKAMs, 314 TOG-SNPs and 389 published marker loci with an average inter-marker distance of 0.59 cM was constructed. Detailed analyses of 1064 mapped loci of this second-generation chickpea genetic map showed a higher degree of synteny with genome of Medicago truncatula, followed by Glycine max, Lotus japonicus and least with Vigna unguiculata. Development of these cost-effective CKAMs for SNP genotyping will be useful not only for genetics research and breeding applications in chickpea, but also for utilizing genome information from other sequenced or model legumes

Preclinical assessment of ulixertinib, a novel ERK1/2 inhibitor

Ulixertinib (BVD-523) is a novel and selective reversible inhibitor of ERK1/ERK2. In xenograft studies it inhibited tumor growth in BRAF-mutant melanoma and colorectal xenografts as well as KRAS-mutant colorectal and pancreatic models. Ulixertinib is currently in Phase I clinical development for the treatment of advance solid tumors. The objective of the study is to assess the metabolic stability (in various pre-clinical and human liver microsomes/hepatocytes), permeability, protein binding, CYP inhibition, CYP induction and CYP phenotyping of ulixertinib. We have also studied the oral and intravenous pharmacokinetics of ulixertinib in mice, rats and dogs. Ulixertinib was found to be moderately to highly stable in various liver microsomes/hepatocytes tested. It is a medium permeable (2.67 x 10-6 cm /sec) drug and a substrate for efflux (efflux ratio: 3.02) in Caco-2 model. Ulixertinib was highly bound to plasma proteins. CYPs involved in its limited metabolism and it is CYP inhibition IC50 ranged between 10-20 μM. Post oral administration ulixertinib exhibited early Tmax (0.50-0.75 h) in mice and rats indicating absorption was rapid, however in dogs Tmax attained at 2 h. The half-life (t½) of ulixertinib by intravenous and oral routes ranged between 1.0-2.5 h across the species. Clearance and volume of distribution by intravenous route for ulixertinib were found to be 6.24 mL/min/kg and 0.56 L/kg; 1.67 mL/min/kg and 0.36 L/kg and 15.5 mL/min/kg and 1.61 L/kg in mice, rats and dogs, respectively. Absolute oral bioavailability in mice and rats was > 92 %, however in dogs it was 34 %

Pathogenic and genetic characterization of six Indian populations of Colletotrichum sublineolum, the causal agent of sorghum anthracnose

The pathogenic and genetic characterization of populations of C. sublineolum, the causal agent of anthracnose of sorghum, was investigated in isolates from 6 locations in India. Multi-location field evaluation and greenhouse tests were done on 16 sorghum lines that comprised the International Sorghum Anthracnose Virulence Nursery (ISAVN). The lines were tested in a field trial for 4-5 years (1992-96) at 6 locations: Indore, Surat, Patancheru, Dharwad, Udaipur and Pantnagar. Plants were scored for disease reaction (R/MR/S) and for disease severity (on a 1-9 scale where 1 is no lesions and 9 is >75% leaf area covered with lesions) at the soft-dough stage in the field and at the seedling stage in the greenhouse. Significant (P<0.001) differences were observed for virulence (disease reaction) and aggressiveness (disease severity) across locations (isolates) and sorghum lines both in field and greenhouse tests. In both tests, isolate x sorghum line interactions were highly significant (P<0.001) suggesting that populations of C. sublineolum at these 6 locations were different. A random amplified polymorphic DNA (RAPD) analysis exhibited genetic dissimilarities among the isolates and these were classified into 6 groups

Genetic variability in trait-specific rice germplasm groups based on coefficient of parentage, SSR markers and fertility restoration

To maximize heterosis, it is important to understand the genetic diversity of germplasm and associate useful phenotypic traits such as fertility restoration for hybrid rice breeding. The objectives of the present study were to characterize genetic diversity within a set of rice germplasm groups using coefficient of parentage (COP) values and 58 simple sequence repeat (SSR) markers for 124 genotypes having different attributes such as resistance/tolerance to various biotic and abiotic stresses. These lines were also used for identifying prospective restorers and maintainers for wild abortive-cytoplasmic male sterile (CMS) line. The mean COP value for all the lines was 0.11, indicating that the genotypes do not share common ancestry. The SSR analysis generated a total of 268 alleles with an average of 4.62 alleles per locus. The mean polymorphism information content value was 0.53, indicating that the markers selected were highly polymorphic. Grouping based on COP analysis revealed three major clusters pertaining to the indica, tropical japonica and japonica lines. A similar grouping pattern with some variation was also observed for the SSR markers. Fertility restoration phenotype based on the test cross of the 124 genotypes with a CMS line helped identify 23 maintainers, 58 restorers and 43 genotypes as either partial maintainers or partial restorers. This study demonstrates that COP analysis along with molecular marker analysis might encourage better organization of germplasm diversity and its use in hybrid rice breeding. Potential restorers identified in the study can be used for breeding high-yielding stress-tolerant medium-duration rice hybrids, while maintainers would prove useful for developing new rice CMS lines

Preclinical assessment of ulixertinib, a novel ERK1/2 inhibitor

Ulixertinib (BVD-523) is a novel and selective reversible inhibitor of ERK1/ERK2. In xenograft studies it inhibited tumor growth in BRAF-mutant melanoma and colorectal xenografts as well as KRAS-mutant colorectal and pancreatic models. Ulixertinib is currently in Phase I clinical development for the treatment of advance solid tumors. The objective of the study is to assess the metabolic stability (in various pre-clinical and human liver microsomes/hepatocytes), permeability, protein binding, CYP inhibition, CYP induction and CYP phenotyping of ulixertinib. We have also studied the oral and intravenous pharmacokinetics of ulixertinib in mice, rats and dogs. Ulixertinib was found to be moderately to highly stable in various liver microsomes/hepatocytes tested. It is a medium permeable (2.67 x 10-6 cm /sec) drug and a substrate for efflux (efflux ratio: 3.02) in Caco-2 model. Ulixertinib was highly bound to plasma proteins. CYPs involved in its limited metabolism and it is CYP inhibition IC50 ranged between 10-20 µM. Post oral administration ulixertinib exhibited early Tmax (0.50-0.75 h) in mice and rats indicating absorption was rapid, however in dogs Tmax attained at 2 h. The half-life (t½) of ulixertinib by intravenous and oral routes ranged between 1.0-2.5 h across the species. Clearance and volume of distribution by intravenous route for ulixertinib were found to be 6.24 mL/min/kg and 0.56 L/kg; 1.67 mL/min/kg and 0.36 L/kg and 15.5 mL/min/kg and 1.61 L/kg in mice, rats and dogs, respectively. Absolute oral bioavailability in mice and rats was > 92 %, however in dogs it was 34 %

Dynamism in the solar core

Recent results of a mixed shell model heated asymmetrically by transient increases in nuclear burning indicate the transient generation of small hot spots inside the Sun somewhere between 0.1 and 0.2 solar radii. These hot bubbles are followed by a nonlinear differential equation system with finite amplitude non-homologous perturbations which is solved in a solar model. Our results show the possibility of a direct connection between the dynamic phenomena of the solar core and the atmospheric activity. Namely, an initial heating about DQ_0 ~ 10^{31}-10^{37} ergs can be enough for a bubble to reach the outer convective zone. Our calculations show that a hot bubble can arrive into subphotospheric regions with DQ_final ~ 10^{28} - 10^{34} ergs with a high speed, up to 10 km s-1, approaching the local sound speed. We point out that the developing sonic boom transforms the shock front into accelerated particle beam injected upwards into the top of loop carried out by the hot bubble above its forefront traveling from the solar interior. As a result, a new perspective arises to explain flare energetics. We show that the particle beams generated by energetic deep-origin hot bubbles in the subphotospheric layers have masses, energies, and chemical compositions in the observed range of solar chromospheric and coronal flares. It is shown how the emergence of a hot bubble into subphotospheric regions offers a natural mechanism that can generate both the eruption leading to the flare and the observed coronal magnetic topology for reconnection. We show a list of long-standing problems of solar physics that our model explains. We present some predictions for observations, some of which are planned to be realized in the near future.Comment: 44 pages, 20 figure

MMTV-Wnt1 and -ΔN89β-Catenin Induce Canonical Signaling in Distinct Progenitors and Differentially Activate Hedgehog Signaling within Mammary Tumors

Canonical Wnt/β-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. A significant proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTV-Wnt1 and MMTV-ΔN89β-catenin develop mammary adenocarcinomas. Many studies have assumed these mouse models of breast cancer to be equivalent. Here we show that MMTV-Wnt1 and MMTV-ΔN89β-catenin transgenes induce tumors with different phenotypes. Using axin2/conductin reporter genes we show that MMTV-Wnt1 and MMTV-ΔN89β-catenin activate canonical Wnt signaling within distinct cell-types. ΔN89β-catenin activated signaling within a luminal subpopulation scattered along ducts that exhibited a K18+ER−PR−CD24highCD49flow profile and progenitor properties. In contrast, MMTV-Wnt1 induced canonical signaling in K14+ basal cells with CD24/CD49f profiles characteristic of two distinct stem/progenitor cell-types. MMTV-Wnt1 produced additional profound effects on multiple cell-types that correlated with focal activation of the Hedgehog pathway. We document that large melanocytic nevi are a hitherto unreported hallmark of early hyperplastic Wnt1 glands. These nevi formed along the primary mammary ducts and were associated with Hedgehog pathway activity within a subset of melanocytes and surrounding stroma. Hh pathway activity also occurred within tumor-associated stromal and K14+/p63+ subpopulations in a manner correlated with Wnt1 tumor onset. These data show MMTV-Wnt1 and MMTV-ΔN89β-catenin induce canonical signaling in distinct progenitors and that Hedgehog pathway activation is linked to melanocytic nevi and mammary tumor onset arising from excess Wnt1 ligand. They further suggest that Hedgehog pathway activation maybe a critical component and useful indicator of breast tumors arising from unopposed Wnt1 ligand