Respiratory syncytial virus activates epidermal growth factor receptor to suppress interferon regulatory factor 1-dependent interferon-lambda and antiviral defense in airway epithelium.

Respiratory syncytial virus (RSV) persists as a significant human pathogen that continues to contribute to morbidity and mortality. In children, RSV is the leading cause of lower respiratory tract infections, and in adults RSV causes pneumonia and contributes to exacerbations of chronic lung diseases. RSV induces airway epithelial inflammation by activation of the epidermal growth factor receptor (EGFR), a tyrosine kinase receptor. Recently, EGFR inhibition was shown to decrease RSV infection, but the mechanism(s) for this effect are not known. Interferon (IFN) signaling is critical for innate antiviral responses, and recent experiments have implicated IFN-λ (lambda), a type III IFN, as the most significant IFN for mucosal antiviral immune responses to RSV infection. However, a role for RSV-induced EGFR activation to suppress airway epithelial antiviral immunity has not been explored. Here, we show that RSV-induced EGFR activation suppresses IFN regulatory factor (IRF) 1-induced IFN-λ production and increased viral infection, and we implicate RSV F protein to mediate this effect. EGFR inhibition, during viral infection, augmented IRF1, IFN-λ, and decreased RSV titers. These results suggest a mechanism for EGFR inhibition to suppress RSV by activation of endogenous epithelial antiviral defenses, which may be a potential target for novel therapeutics.

Analysis of CARD15/NOD2 haplotypes fails to identify common variants associated with rheumatoid arthritis susceptibility.

OBJECTIVES: The CARD15/NOD2 gene product plays an important role in host response to bacterial lipopolysaccharides and bacterial muramyl dipeptide via activation of NF-kappaB in monocytes. Mutations in CARD15 are associated with Crohn's disease (CD), a chronic inflammatory bowel disease. In this study we sought to determine whether CD-associated mutations or any common variants of this gene might contribute to susceptibility to another chronic inflammatory disease, rheumatoid arthritis (RA). METHODS: We genotyped 376 Caucasian RA cases and 376 ethnically matched healthy controls for three CD-associated CARD15 mutations. We also genotyped these 752 individuals for 12 common CARD15 single nucleotide polymorphisms (SNPs), determined the linkage disequilibrium structure of the gene, and compared the frequencies of the common CARD15 haplotypes in the RA cases and controls. RESULTS: None of the CD-associated mutations or the CARD15 SNPs was associated with susceptibility to RA. We also found no significant difference in the frequencies of any of the common haplotypes of the CARD15 gene in RA patients and controls. Our haplotype analysis was consistent with earlier observations that all three CD-associated variants independently arose on the same ancestral haplotype. CONCLUSIONS: These data suggest that CARD15 variants are not associated with RA susceptibility.

Clinical evaluation of pearl millet conophor weaning mix as supplementary food for Nigerian children

The purpose of this study was to formulate a weaning diet from pearl millet-conophor nut flour that would promote growth. For PER, BV, NPU and TD values, casein diet was the most superior while millet-conophor diet and soy-ogi diet compared favourably with each other. For the clinical measurements of the experimental rats on the soy -ogi diet and millet-conophor diet, apart from the urinary urea level of the group on millet conophor diet which was much higher than soy-ogi, there was no difference in any of the other parameters measured. It was therefore, concluded that the millet-conophor, diet was favourably well with the soy-ogi.

Activity pattern, energy intake and obesity among Nigerian urban market women.

Activity pattern, energy intake and body mass index (BMI) were studied in a group of 232 women aged 19-65 years. The subjects were selected from five major markets in Abeokuta Township using a systematic random sampling technique. With the aid of a structured questionnaire and 24-h diet recall, information was collected on socio-demographic characteristics and the food and nutrient intake of the subjects. Information on the activity pattern was collected by recall and random spot observation methods. The result indicated that the majority (61%) of the respondents spent a total of 16 h on both domestic and market activities. An average of 11.5 h was spent in the market on predominantly sedentary activities. The mean energy intake of the women was 3701 kcal (15.4 MJ), which constituted about 164% of the recommended dietary allowance. Roots and tubers, cereals and legume form the major source of nutrients; while fried foods featured prominently in the menu. Eighty-nine women (38.4%) have a BMI within the healthy range of 18.5-25, while a total of 136, representing 58.6%, have a BMI greater than 25. A total of 66 women, representing 48.5% of the 136 women whose BMI was above 25, have a BMI in excess of 30 and are classified as obese. Both the energy intake and activity pattern of the respondents correlated positively with the BMI. This study has established a high risk of obesity among urban market women in Nigeria.

Influence of the N-methyl-D-aspartate antagonist memantine on human motor cortex excitability.

The aim of our study was to investigate the effect of the N-methyl-D-aspartate (NMDA) antagonist memantine on motor excitability in humans. Seven healthy volunteers received memantine or placebo, respectively, over a period of 8 days. At day 8, transcranial magnetic stimulation (TMS) was performed using a paired pulses paradigm in order to assess intracortical inhibition and facilitation. Additionally, motor threshold and silent period duration after TMS were measured as well as M waves, F waves and peripheral silent period after electrical peripheral nerve stimulation. Intracortical inhibition was enhanced, and intracortical facilitation reduced after memantine ingestion in comparison to placebo, whereas no significant difference could be observed regarding the other neurophysiological parameters. We conclude that the NMDA receptor is involved in the regulation of excitability of intracortical interneuronal circuits.

Comparison of a digestion-sedimentation technique with the Kato-Katz technique in the detection and quantification of S. mansoni eggs in light to moderate infections.

A comparison between a digestion-sedimentation technique (DST) and the Kato-Katz thick smear technique (KKT) in the detection and quantification of Schistosoma eggs in stool was carried out in 551 subjects. Specimen were collected one or two years after treatment with praziquantel from subjects living in a schistosomiasis endemic area of Mali. One hundred infections missed by the KKT were detected by the DST. Conversely, 35 infections missed by the DST were detected by the KKT (88% were light infections). More subjects were classified as lightly infected by the DST (p < 10(-3)) and more subjects were classified as moderately infected (101-400 epg) by the KKT (p = 0.02). The KKT produced higher counts than the DST among the youngest age group which was also the most infected. The principal advantage of the DST over the KKT was its better sensitivity to detect light infections resulting from a larger amount of stool processed.

Specific antibody detection in human aspergillosis: a GEMO* multicentre evaluation of a rapid immunoelectrophoresis method (Paragon). Group d'Etude des Mycoses Opportunistes.

A new immunoelectrophoresis system, the Paragon system, was evaluated in three different hospital centres with the aim of improving standardization of the serodiagnosis of human aspergillosis. To select the most efficient antigen, various commercial and home-made antigens were first tested on 19 sera from 19 patients with highly probable aspergillosis. The value measured using the Paragon anti-Aspergillus antibody detection system was then compared with the results obtained by conventional serological diagnostic methods (conventional immunoelectrophoresis, enzyme linked-immunosorbent assay, indirect immunofluorescence): this step was performed using the first 19 sera as well as 16 other sera from 13 patients with suspected aspergillosis. Concordant results were obtained in 28 cases. The discrepancies observed with seven sera were probably related to differences in the nature of the antigens. Paragon immunoelectrophoresis proved to be a practicable technique requiring only a small amount of serum and giving results within a shorter time than competitive methods (24-48 h). Its major drawbacks compared with conventional immunoelectrophoresis are some difficulties in reading, fewer precipitin lines and the relatively high cost of routine analysis.

Phytophotodermatitis mimicking child abuse.

A 13-month-old girl presented with red finger marks on both shoulders thought initially to be secondary to child abuse. The appearance of the marks was not typical of bruising of the stated age and there were no social concerns or other medical features of child abuse. Direct questioning revealed that the mother had been gardening on a sunny day and had picked the child up prior to the appearance of the marks. The marks are thought to represent a phytophotodermatitis. Many paediatric skin conditions can mimic child abuse. Recognition of this further possibility will prevent avoidable errors of diagnosis.

Ovicidal effects of albendazole in human ascariasis, ancylostomiasis and trichuriasis.

Albendazole, a broad spectrum anthelmintic, was administered as a 400 mg single dose to 20 patients harbouring Ascaris (ten cases), hookworms (four cases each of Ancylostoma duodenale and Necator americanus) and trichuriasis (ten cases). Faeces were obtained before treatment and during the following five days. Coprocultures were made for 90 days for Ascaris and Trichuris eggs, hookworm eggs were cultured by the Harada-Mori technique for at least eight days. Albendazole was ovicidal against all four genera of nematodes.