Full Genome of batCoV/MinFul/2018/SriLanka,a Novel Alpha-Coronavirus Detected in Miniopterus fuliginosus,Sri Lanka

Coronaviruses (CoV) are divided into the genera α-CoVs, β-CoVs, γ-CoVs and δ-CoVs. Of these, α-CoVs and β-CoVs are solely capable of causing infections in humans, resulting in mild to severe respiratory symptoms. Bats have been identified as natural reservoir hosts for CoVs belonging to these two genera. Consequently, research on bat populations, CoV prevalence in bats and genetic characterization of bat CoVs is of special interest to investigate the potential transmission risks. We present the genome sequence of a novel α-CoV strain detected in rectal swab samples of Miniopterus fuliginosus bats from a colony in the Wavul Galge cave (Koslanda, Sri Lanka). The novel strain is highly similar to Miniopterus bat coronavirus 1, an α-CoV located in the subgenus of Minunacoviruses. Phylogenetic reconstruction revealed a high identity of the novel strain to other α-CoVs derived from Miniopterus bats, while human-pathogenic α-CoV strains like HCoV-229E and HCoV-NL63 were more distantly related. Comparison with selected bat-related and human-pathogenic strains of the β-CoV genus showed low identities of ~40%. Analyses of the different genes on nucleotide and amino acid level revealed that the non-structural ORF1a/1b are more conserved among α-CoVs and β-CoVs, while there are higher variations in the structural proteins known to be important for host specificity. The novel strain was named batCoV/MinFul/2018/SriLanka and had a prevalence of 50% (66/130) in rectal swab samples and 58% (61/104) in feces samples that were collected from Miniopterus bats in Wavul Galge cave. Based on the differences between strain batCoV/MinFul/2018/SriLanka and human-pathogenic α-CoVs and β-CoVs, we conclude that there is a rather low transmission risk to humans. Further studies in the Wavul Galge cave and at other locations in Sri Lanka will give more detailed information about the prevalence of this virus.     

Embryonal rhabdomyosarcoma of the ampulla of Vater in early childhood: report of a case and review of literature

Embryonal rhabdomyosarcoma of the ampullary region is a very rare childhood tumor (2 reported cases), and herein we describe a child presenting with obstructive jaundice at early age owing to such tumor in the ampullary region. Successful management with multidisciplinary approach is discussed with reference to the literature.     

The effect of estradiol and a combined estradiol/progestagen preparation on insulin sensitivity in healthy postmenopausal women.

Abnormalities of carbohydrate metabolism and insulin sensitivity have been reported in estrogen deficiency. Estrogen replacement appears to result in an improvement in these parameters, although progestagens may antagonize these effects. We have examined the effects of transdermal estradiol and oral norethisterone on insulin sensitivity using the hyperinsulinemic euglycemic clamp method by performing a randomized, double blind, placebo-controlled study in 22 healthy women after a surgically induced menopause. After baseline measurements, subjects were randomized to receive either transdermal 17beta-estradiol (50 microg) or matching placebo patches for 6 weeks. The subjects were then further randomized to receive either estradiol in combination with oral norethisterone (1 mg) or a matching oral placebo preparation, crossing over after 6 weeks, with assessment of insulin sensitivity at the end of each treatment. No significant increase in insulin sensitivity was observed after 6 weeks of transdermal 17beta-estradiol treatment (95% confidence interval, -0.54, 1.86; P = 0.27). Addition of norethisterone for a further 6 weeks had no detectable effect on insulin sensitivity (95% confidence interval, -1.65, 1.10; P = 0.65). The results of this study using transdermal estradiol do not support previous reports that unopposed estrogens exert potentially beneficial effects on insulin sensitivity and suggest that the addition of an oral progestagen confers no clinically important risk or benefit. It is therefore unlikely that effects on insulin sensitivity contribute appreciably to the cardioprotective benefits attributed to hormone replacement therapy.     

Coadministration of HIV vaccine vectors with vaccinia viruses expressing IL-15 but not IL-2 induces long-lasting cellular immunity

Vaccine efficacy is determined largely by cellular and humoral immunity as well as long-lasting immunological memory. IL-2 and IL-15 were evaluated in vaccinia vectors expressing HIV gp160 for the establishment of an effective vaccine strategy. Both IL-2 and IL-15 in the vaccinia vector induced strong and long-lasting antibody-mediated immunity as well as a short-term cytotoxic T cell response against HIV gp120. In addition, IL-15 also supported robust CD8+ T cell-mediated long-term immunity, whereas the CD8+ T cell-mediated immunity induced by IL-2 was short-lived. Moreover, we found that the cytokine milieu at the time of priming had surprisingly persistent effects on the character of the memory CD8 T cells long afterward with respect to their fate, functional activities, cytokine receptor expression, and antigen-independent proliferation.     

Early wheezing phenotypes and cognitive development of 3‐yr‐olds. Community‐recruited birth cohort study

Jedrychowski W, Perera FP, Jankowski J, Maugeri U, Mrozek‐Budzyn D, Mroz E, Flak E, Skarupa A, Edwards S, Lisowska‐Miszczyk I. Early wheezing phenotypes and cognitive development of 3‐yr‐olds. Community‐recruited birth cohort study.
Pediatr Allergy Immunol 2010: 21: 550–556.
© 2009 John Wiley & Sons A/S The main purpose of the study was to answer the question whether young children without clinical diagnosis of asthma but experiencing early wheezing disorders and therefore being at high risk of developing asthma may have cognitive deficits. In the ongoing birth cohort study wheezing symptoms were recorded postpartum over two first years of age and subsequently cognitive status of children at the age of 3 yr was assessed with the Bayley Mental Development Index (MDI). In the statistical analysis a wide range of modifying and confounding factors (maternal education, gender of children, prenatal exposure to lead and environmental tobacco smoke (ETS) were considered to assess the independent effect of early wheezing phenotypes on cognitive development of children. The MDI score correlated inversely with the number of wheezing days recorded over 24 months (r = ?0.13, p = 0.007), lead cord blood concentration (r = ?0.12, p = ?0.02), number of siblings (r = ?0.17, p = 0.0006) and the number of cigarettes smoked daily by other household members at home over the pregnancy period (r = ?0.18, p = 0.0002). While the children who experienced wheezing over the first year of age showed deficit of 2 MDI scores (beta coeff. = ?2.31, 95%CI: ?4.63 to 0.02), those with persistent wheezing had the score deficit of 4 points (beta coeff. = ?4.41, 95%CI: ?8.27 to ?0.55). To our knowledge, it is the first report in the iterature showing that early wheezing is associated the cognitive deficit in a community‐recruited very young children. Observed cognitive deficit in early wheezers may be caused by RSV infections or can be related to lower lung function attributed to persistent wheezing, which reducing oxygen supply would affect rapidly developing brain.     

Molecular epidemiology and biomarkers in etiologic cancer research: the new in light of the old.

The purpose of this review is to evaluate progress in molecular epidemiology over the past 24 years in cancer etiology and prevention to draw lessons for future research incorporating the new generation of biomarkers. Molecular epidemiology was introduced in the study of cancer in the early 1980s, with the expectation that it would help overcome some major limitations of epidemiology and facilitate cancer prevention. The expectation was that biomarkers would improve exposure assessment, document early changes preceding disease, and identify subgroups in the population with greater susceptibility to cancer, thereby increasing the ability of epidemiologic studies to identify causes and elucidate mechanisms in carcinogenesis. The first generation of biomarkers has indeed contributed to our understanding of risk and susceptibility related largely to genotoxic carcinogens. Consequently, interventions and policy changes have been mounted to reduce risk from several important environmental carcinogens. Several new and promising biomarkers are now becoming available for epidemiologic studies, thanks to the development of high-throughput technologies and theoretical advances in biology. These include toxicogenomics, alterations in gene methylation and gene expression, proteomics, and metabonomics, which allow large-scale studies, including discovery-oriented as well as hypothesis-testing investigations. However, most of these newer biomarkers have not been adequately validated, and their role in the causal paradigm is not clear. There is a need for their systematic validation using principles and criteria established over the past several decades in molecular cancer epidemiology.