High incidence of vertebral fractures in children with acute lymphoblastic leukemia 12 months after the initiation of therapy

Purpose: Vertebral fractures due to osteoporosis are a potential complication of childhood acute lymphoblastic leukemia (ALL). To date, the incidence of vertebral fractures during ALL treatment has not been reported. Patient and Methods: We prospectively evaluated 155 children with ALL during the first 12 months of leukemia therapy. Lateral thoracolumbar spine radiographs were obtained at baseline and 12 months. Vertebral bodies were assessed for incident vertebral fractures using the Genant semiquantitative method, and relevant clinical indices such as spine bone mineral density (BMD), back pain, and the presence of vertebral fractures at baseline were analyzed for association with incident vertebral fractures. Results: Of the 155 children, 25 (16%; 95% CI, 11% to 23%) had a total of 61 incident vertebral fractures, of which 32 (52%) were moderate or severe. Thirteen (52%) of the 25 children with incident vertebral fractures also had fractures at baseline. Vertebral fractures at baseline increased the odds of an incident fracture at 12 months by an odds ratio of 7.3 (95% CI, 2.3 to 23.1; P = .001). In addition, for every one standard deviation reduction in spine BMD Z-score at baseline, there was 1.8-fold increased odds of incident vertebral fracture at 12 months (95% CI, 1.2 to 2.7; P = .006). Conclusion: Children with ALL have a high incidence of vertebral fractures after 12 months of chemotherapy, and the presence of vertebral fractures and reductions in spine BMD Z-scores at baseline are highly associated clinical features. © 2012 by American Society of Clinical Oncology

In Vitro Effect of Porphyromonas gingivalis Methionine Gamma Lyase on Biofilm Composition and Oral Inflammatory Response

Methanethiol (methyl mercaptan) is an important contributor to oral malodour and periodontal tissue destruction. Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum are key oral microbial species that produce methanethiol via methionine gamma lyase (mgl) activity. The aim of this study was to compare an mgl knockout strain of P. gingivalis with its wild type using a 10-species biofilm co-culture model with oral keratinocytes and its effect on biofilm composition and inflammatory cytokine production. A P. gingivalis mgl knockout strain was constructed using insertion mutagenesis from wild type W50 with gas chromatographic head space analysis confirming lack of methanethiol production. 10-species biofilms consisting of Streptococcus mitis, Streptococcus oralis, Streptococcus intermedius, Fusobacterium nucleatum ssp polymorphum, Fusobacterium nucleatum ssp vincentii, Veillonella dispar, Actinomyces naeslundii, Prevotella intermedia and Aggregatibacter actinomycetemcomitans with either the wild type or mutant P. gingivalis were grown on Thermanox cover slips and used to stimulate oral keratinocytes (OKF6-TERT2), under anaerobic conditions for 4 and 24 hours. Biofilms were analysed by quantitative PCR with SYBR Green for changes in microbial ecology. Keratinocyte culture supernatants were analysed using a multiplex bead immunoassay for cytokines. Significant population differences were observed between mutant and wild type biofilms; V. dispar proportions increased (p<0.001), whilst A. naeslundii (p<0.01) and Streptococcus spp. (p<0.05) decreased in mutant biofilms. Keratinocytes produced less IL-8, IL-6 and IL-1α when stimulated with the mutant biofilms compared to wild type. Lack of mgl in P. gingivalis has been shown to affect microbial ecology in vitro, giving rise to a markedly different biofilm composition, with a more pro-inflammatory cytokine response from the keratinocytes observed. A possible role for methanethiol in biofilm formation and cytokine response with subsequent effects on oral malodor and periodontitis is suggested

A Study on the Transport and Distribution of Atmospheric Aerosols and its Influence on Regional Meteorological Parameters over the Indian Subcontinent

This doctoral thesis addresses the growing concern about the significant changes in the climatic and weather patterns due to the aerosol loading that have taken place in the Indo Gangetic Plain(IGP)which includes most of the Northern Indian region. The study region comprises of major industrial cities in India (New Delhi, Kanpur, Allahabad, Jamshedpur and Kolkata). Northern and central parts of India are one of the most thickly populated areas in the world and have the most intensely farmed areas. Rapid increase in population and urbanization has resulted in an abrupt increase in aerosol concentrations in recent years. The IGP has a major source of coal; therefore most of the industries including numerous thermal power plants that run on coal are located around this region. They inject copious amount of aerosols into the atmosphere. Moreover, the transport of dust aerosols from arid locations is prevalent during the dry months which increase the aerosol loading in theatmosphere. The topography of the place is also ideal for the congregation of aerosols. It is bounded by the Himalayas in the north, Thar Desert in the west, the Vindhyan range in the south and Brahmaputra ridge in the east. During the non‐monsoon months (October to May) the weather in the location is dry with very little rainfall. Surface winds are weak during most of the time in this dry season. The aerosols that reach the location by means of long distance transport and from regional sources get accumulated under these favourable conditions. The increase in aerosol concentration due to the complex combination of aerosol transport and anthropogenic factors mixed with the contribution from the natural sources alters the optical properties and the life time of clouds in the region. The associated perturbations in radiative balance have a significant impact on the meteorological parameters and this in turn determines the precipitation forming process. Therefore, any change in weather which disturbs the normal hydrological pattern is alarming in the socio‐economic point of view. Hence, the main focus of this work is to determine the variation in transport and distribution of aerosols in the region and to understand the interaction of these aerosols with meteorological parameters and cloud properties.Department of Atmospheric Sciences, Cochin University of Science and Technolog

Aerosol black carbon over a tropical coastal location: response to mesoscale and synoptic scale processes

Continuous ground based measurements on the mass concentration of aerosol Black Carbon (BC) were carried out during January 2004 to December 2004, at a tropical coastal station, Trivandrum, India. These are examined to delineate the response of BC to changes in synoptic as well as mesoscale circulations. BC shows a diurnal (with a nocturnal peak and afternoon low) and seasonal variations (highest during local winter when dry conditions prevail, with a continental airmass and sparse precipitation, and lowest during monsoon when the airmass is marine in nature and precipitation is widespread). The diurnal varations are compared with those from an inland station Kharagpur (at the Northeast part of India) during a campaign mode experiment and the differences are outlined for the month of December 2004. Though the diurnal variations are similar, BC concentrations at Kharagpur were significantly higher than that at Trivandrum for the month of December

Moisture variability over the Indo-Pacific region and its influence on the Indian summer monsoon rainfall

The Indo-Pacific Ocean (i.e. region between 30E and 150E) has been experiencing a spread warming since the 1950s. At the same time the large-scale summer monsoon rainfall over India and the moisture over the East Africa/Arabian Sea are both decreasing. In this study we intend to investigate how the decrease of moisture over the East Africa/Arabian Sea is related with the Indo-Pacific Ocean warming and how this could affect the variability of the Indian summer monsoon rainfall. We performed the analysis for the period 1951-2012 based on observed precipitation, sea surface temperature and atmospheric reanalysis products and we verified the robustness of the result by comparing different datasets. The decreasing trend of moisture over the East Africa/Arabian Sea coincides with an increasing trend of moisture over the western Pacific region. This is accompanied by the strengthening (weakening) of the upward motion over the western Pacific (East Africa/Arabian Sea) that, consequently, contributes in strengthening the western Pacific-Indian Ocean Walker circulation. Associated with it, the low-level westerlies are weakening over the peninsular India, thus contributing to the reduction of moisture transport towards India. Therefore, rainfall has decreased over the Western Ghats and central-east India. Differently from previous decades, since 2003 moisture over the East Africa/Arabian Sea started to increase and this is accompanied by the strengthening of convection due to increased warming of sea surface temperature over the western Arabian Sea. Despite this moisture increase over the Arabian sea, we found that moisture transport is still weakening over the Indian landmass in the very recent decade and still contributing to the decreased precipitation over the northeast India and southern part of the Western Ghats

Iron chelation efficiency of deferasirox (Exjade (R), ICL670) in patients with transfusional hemosiderosis

Iron excretion can be calculated according to Angelucci et al (NEJM 2000). As applied to the novel oral iron chelator deferasirox (DSX), chelation efficiency can then be determined as the % iron excretion vs theoretical iron binding capacity of chelator dose: % efficiency = [iron excretion (mg/kg/day)/chelator dose (mg/kg/day)] x [374/56] x 2 x 100 (374 and 56 represent the molecular weights of DSX and iron; factor 2 accounts for the tridentate ligand). In a total of 325 patients with ß-thalassemia (n=285) or rare anemias, such as MDS (n=13), DBA (n=14) or other anemias (n=13), included in the DSX Phase II and III Studies 0108 and 0107, liver iron concentration (LIC) was evaluated by liver biopsy at baseline and study end. All patients were treated with once-daily oral DSX 5, 10, 20 or 30 mg/kg according to baseline LIC (2-3, >3-7, >7-14 and >14 mg Fe/g dw, respectively). In these patients, the average dose during study was 22.8 ± 7.6 mg/kg. The average iron intake was 0.37 mg/kg/day and was similar between dose cohorts