Infectious complications during therapy of acute leukaemia in Saudi Arabia

In 40 febrile neutropenic episodes during the induction and consolidation chemotherapy of acute leukaemia in Riyadh, 51% of organisms causing septicaemia were gram-negative, 26% gram-positive, 8% anaerobes and 15% fungi. In 21 (52%) febrile episodes there were pulmonary infiltrates; of the 12 where aetiology was known, six were due to fungi. Pulmonary infiltrates progressed to adult respiratory distress syndrome and death in nine instances. There was no significant occurrence of parasitic and tropical infections. The results show that the pattern of infections, during therapy of acute leukaemia in developing countries, may have important differences when compared with western centres. Empiric amphotericin B may need to be introduced at an earlier stage in patients with persistent fever or progressive pulmonary infiltrates.

Efficient and bright polymer light emitting field effect transistors

Light emitting field effect transistors (LEFETs) are emerging as a multi-functional class of optoelectronic devices. LEFETs can simultaneously execute light emission and the standard logic functions of a transistor in a single architecture. However, current LEFET architectures deliver either high brightness or high efficiency but not both concurrently, thus limiting their use in technological applications. Here we show an LEFET device strategy that simultaneously improves brightness and efficiency. The key step change in LEFET performance arises from the bottom gate top-contact device architecture in which the source/drain electrodes are semitransparent and the active channel contains a bi-layer comprising of a high mobility charge-transporting polymer, and a yellow-green emissive polymer. A record external quantum efficiency (EQE) of 2.1% at 1000cd/m2 is demonstrated for polymer based bilayer LEFETs.

ITO-free top emitting organic light emitting diodes with enhanced light out-coupling

Bottom emitting organic light emitting diodes (OLEDs) can suffer from lower external quantum efficiencies (EQE) due to inefficient out-coupling of the generated light. Herein, it is demonstrated that the current efficiency and EQE of red, yellow, and blue fluorescent single layer polymer OLEDs is significantly enhanced when a MoOx(5 nm)/Ag(10 nm)/MoOx(40 nm) stack is used as the transparent anode in a top emitting OLED structure. A maximum current efficiency and EQE of 21.2 cd/A and 6.7%, respectively, was achieved for a yellow OLED, while a blue OLED achieved a maximum of 16.5 cd/A and 10.1%, respectively. The increase in light out-coupling from the top-emitting OLEDs led to increase in efficiency by a factor of up to 2.2 relative to the optimised bottom emitting devices, which is the best out-coupling reported using solution processed polymers in a simple architecture and a significant step forward for their use in large area lighting and displays.

Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA

Rationale: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies. Objectives: To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations. Methods: The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P<5x10-8) and three variants reported as suggestive (P<5×10-7). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever. Main Results: We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4×10-9). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (PStage1+Stage2 = 1.1x10-9), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (PStage1+Stage2 = 1.1x10-8), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status. Conclusions: Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma. © 2012 Ramasamy et al.

Differences in grass pollen allergen exposure across Australia

Objective Allergic rhinitis and allergic asthma are important chronic diseases posing serious public health issues in Australia with associated medical, economic, and societal burdens. Pollen are significant sources of clinically relevant outdoor aeroallergens, recognised as both a major trigger for, and cause of, allergic respiratory diseases. This study aimed to provide a national, and indeed international, perspective on the state of Australian pollen data using a large representative sample. Methods Atmospheric grass pollen concentration is examined over a number of years within the period 1995 to 2013 for Brisbane, Canberra, Darwin, Hobart, Melbourne, and Sydney, including determination of the clinical' grass pollen season and grass pollen peak. Results The results of this study describe, for the first time, a striking spatial and temporal variability in grass pollen seasons in Australia, with important implications for clinicians and public health professionals, and the Australian grass pollen-allergic community. Conclusions These results demonstrate that static pollen calendars are of limited utility and in some cases misleading. This study also highlights significant deficiencies and limitations in the existing Australian pollen monitoring and data. Implications: Establishment of an Australian national pollen monitoring network would help facilitate advances in the clinical and public health management of the millions of Australians with asthma and allergic rhinitis.

The enigma of IgE+ B-cell memory in human subjects

Our understanding of the origin and fate of the IgE-switched B cell has been markedly improved by studies in mouse models. The immediate precursor of the IgE-switched B cell is either a relatively naive nonswitched B cell or a mature IgG-switched B cell. These 2 routes are referred to as the direct and indirect pathways, respectively. IgE responses derived from each pathway differ significantly, largely reflecting the difference in time spent in a germinal center and thus time for clonal expansion, somatic hypermutation, affinity maturation, and acquisition of a memory phenotype. The clinical and therapeutic implications for IgE responses in human subjects are still a matter of debate, largely because the immunization procedures used in the animal models are significantly different from classical atopic sensitization to allergens from pollen and mites. On the basis of the limited information available, it seems likely that these atopic IgE responses are characterized by a relatively low IgG/IgE ratio, low B-cell memory, and modest affinity maturation, which fits well with the direct switching pathway. It is still unresolved how the IgE response evolves to cover a wide epitope repertoire involving many epitopes per allergen, as well as many different allergens from a single allergen source. © 2013 American Academy of Allergy, Asthma & Immunology.

Molecular cloning, expression and immunological characterisation of Pas n 1, the major allergen of Bahia grass Paspalum notatum pollen

Bahia grass, Paspalum notatum, is a clinically important subtropical grass with a prolonged pollination season from spring to autumn. We aimed to clone and characterise the major Bahia grass pollen allergen, Pas n 1. Grass pollen-allergic patients presenting to a tertiary hospital allergy clinic were tested for IgE reactivity with Bahia grass pollen extract by skin prick testing, ImmunoCAP, ELISA and immunoblotting. Using primers deduced from the N-terminal peptide sequence of a group 1 allergen of Bahia grass pollen extract separated by two-dimensional gel electrophoresis, the complete Pas n 1 cDNA was obtained by rapid amplification of cDNA ends and cloned. Biological relevance of recombinant Pas n 1 expressed in Escherichia coli was assessed by serum IgE reactivity and basophil activation. Twenty-nine of 34 (85%) consecutive patients presenting with grass pollen allergy were skin prick test positive to Bahia grass pollen. The Pas n 1 cDNA has sequence homology with the β-expansin 1 glycoprotein family and is more closely related to the maize pollen group 1 allergen (85% identity) than to ryegrass Lol p 1 or Timothy grass Phl p 1 (64 and 66% identity, respectively). rPas n 1 reacted with serum IgE in 47 of 55 (85%) Bahia grass pollen-allergic patients, activated basophils and inhibited serum IgE reactivity with the 29 kDa band of Bahia grass pollen extract. In conclusion the cDNA for the major group 1 allergen of the subtropical Bahia grass pollen, Pas n 1, was identified and cloned. rPas n 1 is immunologically active and is a valuable reagent for diagnosis and specific immunotherapy of grass pollen allergy.

Bahia grass pollen specific IgE is common in seasonal rhinitis patients but has limited cross-reactivity with Ryegrass

Background: Perennial Ryegrass is a major cause of rhinitis in spring and early summer. Bahia grass, Paspalum notatum, flowers late into summer and could account for allergic rhinitis at this time. We determined the frequency of serum immunoglobulin (Ig)E reactivity with Bahia grass in Ryegrass pollen allergic patients and investigated IgE cross-reactivity between Bahia and Ryegrass. Methods: Serum from 33 Ryegrass pollen allergic patients and 12 nonatopic donors were tested for IgE reactivity with Bahia and Ryegrass pollen extracts (PE) by enzyme-linked immunosorbent assay (ELISA), western blotting and inhibition ELISA. Allergen-specific antibodies from a pool of sera from allergic donors were affinity purified and tested for IgE cross-reactivity. Results: Seventy-eight per cent of the sera had IgE reactivity with Bahia grass, but more weakly than with Ryegrass. Antibodies eluted from the major Ryegrass pollen allergens, Lol p 1 and Lol p 5, showed IgE reactivity with allergens of Ryegrass and Canary but not Bahia or Bermuda grasses. Timothy, Canary and Ryegrass inhibited IgE reactivity with Ryegrass and Bahia grass, whereas Bahia, Johnson and Bermuda grass did not inhibit IgE reactivity with Ryegrass. Conclusions: The majority of Ryegrass allergic patients also showed serum IgE reactivity with Bahia grass PE. However, Bahia grass and Ryegrass had only limited IgE cross-reactivity indicating that Bahia grass should be considered in diagnosis and treatment of patients with hay fever late in' the grass pollen season.

Molecular mimicry: Can epitope mimicry induce autoimmune disease?

Mimicry of host antigens by infectious agents may induce cross-reactive autoimmune responses to epitopes within host proteins which, in susceptible individuals, may tip the balance of immunological response versus tolerance toward response and subsequently lead to autoimmune disease. Epitope mimicry may indeed be involved in the pathogenesis of several diseases such as post-viral myocarditis or Chagas disease, but for many other diseases in which it has been implicated, such as insulin-dependent diabetes mellitis or rheumatoid arthritis, convincing evidence is still lacking. Even if an epitope mimic can support a cross-reactive T or B cell response in vitro, its ability to induce an autoimmune disease in vivo will depend upon the appropriate presentation of the mimicked host antigen in the target tissue and, in the case of T cell mimics, the ability of the mimicking epitope to induce a proliferative rather than anergizing response upon engagement of the MHC-peptide complex with the T cell receptor. B cell presentation of mimicking foreign antigen to T cells is a possible mechanism for instigating an autoimmune response to self antigens that in turn can lead to autoimmune disease under particular conditions of antigen presentation, secondary signalling and effector cell repertoire. In this review evidence in support of epitope mimicry is examined in the light of the necessary immunological considerations of the theory.

Simultaneous kinetic spectrometric determination of three flavonoid antioxidants in fruit with the aid of chemometrics

A simple, inexpensive and sensitive kinetic spectrophotometric method was developed for the simultaneous determination of three anti-carcinogenic flavonoids: catechin, quercetin and naringenin, in fruit samples. A yellow chelate product was produced in the presence neocuproine and Cu(I) – a reduction product of the reaction between the flavonoids with Cu(II), and this enabled the quantitative measurements with UV–vis spectrophotometry. The overlapping spectra obtained, were resolved with chemometrics calibration models, and the best performing method was the fast independent component analysis (fast-ICA/PCR (Principal component regression)); the limits of detection were 0.075, 0.057 and 0.063 mg L−1 for catechin, quercetin and naringenin, respectively. The novel method was found to outperform significantly the common HPLC procedure.

Acute infectious diarrhea lessons learned from the past?

The Journal of Pediatric Gastroenterology and Nutrition (JPGN) has been at the forefront of many of the seminal advances into research on infectious diarrhea. In 1982, the first article of the JPGN was entitled “Oral Therapy for Dehydration in Diarrheal Diseases as a Global Problem” and has set the scene for several thousand subsequent articles. In his initial editorial, Finberg (1) posed several questions, which still have relevance 30 years later: 1. When is oral rehydration not appropriate, if ever? 2. What should be the composition of the oral solution and should there be more than one? 3. Should recommended practice be different in lesser-developed countries from those in developed countries? 4. Should the salts and glucose be prepackaged or should home supplies be used by instructed mothers? 5. When should standard feedings be resumed?

Observations of road safety behaviours and practices of motorcycle rickshaw drivers in Lahore, Pakistan

Motorcycle Rickshaws (MRs) are an informal paratransit mode in Pakistan. They are locally manufactured and very popular but there are concerns about their crash involvement and overall safety. The first study of the current PhD program revealed that rickshaws (both MRs and auto-rickshaws) were involved in 51,992 road crashes attended by emergency ambulances in Punjab province, Pakistan between 2011-2013. This study aims to examine the road safety behaviours and practices of Motorcycle Rickshaw Drivers (MRDs) that may be contributing to these crashes. MRDs were observed at 12 major signalised intersections in Lahore. Vehicle characteristics and driver behaviours were recorded using a paper-based survey between 9am-7pm for a full week in May 2015. Of the 500 MRDs observed, about 23.4% appeared to be younger than the minimum driver licensing age of 18 years. More than half (52.6%) of the MRDs entered on the red light and 17.4% crossed when the signal was turning from yellow to green or red. MR traffic conflicts were observed in 62.8% of cases and one crash and 15 near-miss crashes were witnessed. Additionally, about half of MRs were overloaded, no MRD wore a helmet, and 3.8% were using a mobile phone while driving. This study provides the first scientific evidence to substantiate public concerns regarding the safety of MRs. It demonstrates that about a quarter of MRDs are underage,almost half of MRs are overloaded and more than half disobey traffic signals. This research could inform authorities to manage MR related transport and road safety issues.

One device, two doses

Ms Breathless is a 59-year-old lady living with chronic obstructive pulmonary disease (COPD) for several years now, and quit smoking over 20 years ago. She sometimes experiences symptoms of breathlessness, and an unrelenting productive cough, particularly when she comes in contact with dusty places, second-hand smoke, or when her allergies and hay fever play up. Apart from these triggers, her symptoms are well maintained with her inhalers glycopyrronium bromide (Seebri) and indacaterol (Onbrez), and she has been using them for about nine months. Ms Breathless is otherwise healthy, and not taking any other medicines.