Study of rare semileptonic Bc+→D+ννˉB_c^+ \to D^+ \nu \bar{\nu} decay in the light-cone quark model

We study the exclusive semileptonic rare $B_c^+ \to D^+ \nu \bar{\nu}$ decay in the framework of light-cone quark model. The transition form factors $f_{+}(q^2)$ and $f_{T}(q^2)$ are evaluated in the time-like region using the analytic continuation method in $q^{+} = 0$ frame. The analytic solutions of these form factors are compared with the results obtained from the double pole parametric form. The branching ratio for $B_c^+ \to D^+ \nu \bar{\nu}$ decay is calculated and compared with the other theoretical model predictions. The predicted results in this model can be tested at the LHCb experiments in near future which will help in testing the unitarity of CKM quark mixing matrix, thus, providing an insight into the phenomenon of CP violation.Comment: 14 pages, 4 figure

Impact of different grades of anaemia severity during pregnancy on maternal and neonatal outcomes: a prospective study

Background: Anaemia in pregnancy is a universal health problem that may cause a number of obstetrical and neonatal complications. This prospective observational study aims to evaluate and compare maternal and neonatal outcomes in different grades of anaemia severity.Methods: A total of 400 pregnant women with anaemia in third trimester were classified into three groups according to haemoglobin (Hb) levels-group I with Hb:10-10.9 g/dl, group II with Hb:7-9.9g/dl and group III with Hb<7 g/dl. Maternal and neonatal outcomes of women with different severity of anaemia were analyzed and compared. Two groups means were compared by Student’s t-independent test and more than two groups means by one way analysis of variance test followed by post-hoc pairwise comparison using Bonferroni test.Results: The prevalence of anaemia in the study population was 35.2%. Mild, moderate and severe anaemia were found in 58% (n=232), 29.0% (n=116) and 13% (n=52) women respectively. A statistically significant difference in maternal outcomes such as Preterm labor (p=0.001), Prelabor premature rupture of membranes (p=0.044), Intrauterine growth restriction (p=0.002) and postpartum hemorrhage (p=0.001) was observed amongst the three groups. Cardiac failure occurred in 26.9% (n=14) and mortality in 13.4% (n=7) women with severe anaemia. Amongst the neonatal morbidities, the rate of low birth weight, preterm birth, respiratory distress syndrome, septicaemia, pneumonitis and jaundice revealed an increasing trend with rising severity of anaemia which was statistically significant.Conclusions: Targeted interventions addressing early detection and appropriate treatment in early pregnancy can prevent and avoid dismal maternal and neonatal consequences

Cystic fibrosis presenting as small bowel obstruction in pediatric patient: a case report

Intestinal obstruction complete or incomplete has been found commonly in patients with cystic fibrosis in all age groups with variable presentation. Prevalence of intestinal obstruction in children with cystic fibrosis is 7-8%. Neonates present with meconium ileus due to inspissated meconium and complete obstruction. This case demonstrates similar presentation in a pediatric patient. A six day old male patient presented in the pediatric surgery department with abdominal distention, vomiting and fever. Patient was operated and intraoperative meconium plug was seen along with dilated proximal bowel, filled with sticky meconium. Resected gut segment was received in the Department of Pathology. Grossly dilated gut segment on cut section was seen filled with thick putty like greenish fecal matter. Histopathological examination showed features consistent with cystic fibrosis. There are multiple causes for intestinal obstruction in neonates, cystic fibrosis can be one of them which needs to be considered by the clinicians. Such cases need to be reported for better understanding of their clinico-pathological presentation and prevalence

Impact of repeated NeemAzal®-treated blood meals on the fitness of Anopheles stephensi mosquitoes

Background: Herbal remedies are widely used in many malaria endemic countries to treat patients, in particular in the absence of anti-malarial drugs and in some settings to prevent the disease. Herbal medicines may be specifically designed for prophylaxis and/or for blocking malaria transmission to benefit both, the individual consumer and the community at large. Neem represents a good candidate for this purpose due to its inhibitory effects on the parasite stages that cause the clinical manifestations of malaria and on those responsible for infection in the vector. Furthermore, neem secondary metabolites have been shown to interfere with various physiological processes in insect vectors. This study was undertaken to assess the impact of the standardised neem extract NeemAzal® on the fitness of the malaria vector Anopheles stephensi following repeated exposure to the product through consecutive blood meals on treated mice. Methods: Batches of An. stephensi mosquitoes were offered 5 consecutive blood meals on female BALB/c mice treated with NeemAzal® at an azadirachtin A concentration of 60, 105 or 150 mg/kg. The blood feeding capacity was estimated by measuring the haematin content of the rectal fluid excreted by the mosquitoes during feeding. The number of eggs laid was estimated by image analysis and their hatchability assessed by direct observations. Results: A dose and frequency dependent impact of NeemAzal® treatment on the mosquito feeding capacity, oviposition and egg hatchability was demonstrated. In the 150 mg/kg treatment group, the mosquito feeding capacity was reduced by 50% already at the second blood meal and by 50 to 80% in all treatment groups at the fifth blood meal. Consequently, a 50 – 65% reduction in the number of eggs laid per female mosquito was observed after the fifth blood meal in all treatment groups. Similarly, after the fifth treated blood meal exposure, hatchability was found to be reduced by 62% and 70% in the 105 and 150 mg/kg group respectively. Conclusions: The findings of this study, taken together with the accumulated knowledge on neem open the challenging prospects of designing neem-based formulations as multi-target phytomedicines exhibiting preventive, parasite transmission-blocking as well as anti-vectorial properties. Keywords: Malaria, Vectors, Neem, Azadirachtin, Transmission-blocking, Anti-vectoria

Salinomycin and Other Ionophores as a New Class of Antimalarial Drugs with Transmission-Blocking Activity

The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual stages of Plasmodium, thus with both curative and transmission-blocking activities. The aim of the present work was to investigate whether the class of monovalent ionophores, which includes drugs used in veterinary medicine and that were recently proposed as human anticancer agents, meets these requirements. The activity of salinomycin, monensin, and nigericin on Plasmodium falciparum asexual and sexual erythrocytic stages and on the development of the Plasmodium berghei and P. falciparum mosquito stages is reported here. Gametocytogenesis of the P. falciparum strain 3D7 was induced in vitro, and gametocytes at stage II and III or stage IV and V of development were treated for different lengths of time with the ionophores and their viability measured with the parasite lactate dehydrogenase (pLDH) assay. The monovalent ionophores efficiently killed both asexual parasites and gametocytes with a nanomolar 50% inhibitory concentration (IC50). Salinomycin showed a fast speed of kill compared to that of standard drugs, and the potency was higher on stage IV and V than on stage II and III gametocytes. The ionophores inhibited ookinete development and subsequent oocyst formation in the mosquito midgut, confirming their transmission-blocking activity. Potential toxicity due to hemolysis was excluded, since only infected and not normal erythrocytes were damaged by ionophores. Our data strongly support the downstream exploration of monovalent ionophores for repositioning as new antimalarial and transmission-blocking leads

Plasmodium transmission blocking activities of Vernonia amygdalina extracts and isolated compounds

BACKGROUND: Medicinal plants are a validated source for discovery of new leads and standardized herbal medicines. The aim of this study was to assess the activity of Vernonia amygdalina leaf extracts and isolated compounds against gametocytes and sporogonic stages of Plasmodium berghei and to validate the findings on field isolates of Plasmodium falciparum. METHODS: Aqueous (Ver-H2O) and ethanolic (Ver-EtOH) leaf extracts were tested in vivo for activity against sexual and asexual blood stage P. berghei parasites. In vivo transmission blocking effects of Ver-EtOH and Ver-H2O were estimated by assessing P. berghei oocyst prevalence and density in Anopheles stephensi mosquitoes. Activity targeting early sporogonic stages (ESS), namely gametes, zygotes and ookinetes was assessed in vitro using P. berghei CTRPp.GFP strain. Bioassay guided fractionation was performed to characterize V. amygdalina fractions and molecules for anti-ESS activity. Fractions active against ESS of the murine parasite were tested for ex vivo transmission blocking activity on P. falciparum field isolates. Cytotoxic effects of extracts and isolated compounds vernolide and vernodalol were evaluated on the human cell lines HCT116 and EA.hy926. RESULTS: Ver-H2O reduced the P. berghei macrogametocyte density in mice by about 50% and Ver-EtOH reduced P. berghei oocyst prevalence and density by 27 and 90%, respectively, in An. stephensi mosquitoes. Ver-EtOH inhibited almost completely (>90%) ESS development in vitro at 50 μg/mL. At this concentration, four fractions obtained from the ethylacetate phase of the methanol extract displayed inhibitory activity >90% against ESS. Three tested fractions were also found active against field isolates of the human parasite P. falciparum, reducing oocyst prevalence in Anopheles coluzzii mosquitoes to one-half and oocyst density to one-fourth of controls. The molecules and fractions displayed considerable cytotoxicity on the two tested cell-lines. CONCLUSIONS: Vernonia amygdalina leaves contain molecules affecting multiple stages of Plasmodium, evidencing its potential for drug discovery. Chemical modification of the identified hit molecules, in particular vernodalol, could generate a library of druggable sesquiterpene lactones. The development of a multistage phytomedicine designed as preventive treatment to complement existing malaria control tools appears a challenging but feasible goal