Deletion within the Src homology domain 3 of Bruton's tyrosine kinase resulting in X-linked agammaglobulinemia (XLA).

The gene responsible for X-linked agammaglobulinemia (XLA) has been recently identified to code for a cytoplasmic tyrosine kinase (Bruton's agammaglobulinemia tyrosine kinase, BTK), required for normal B cell development. BTK, like many other cytoplasmic tyrosine kinases, contains Src homology domains (SH2 and SH3), and catalytic kinase domain. SH3 domains are important for the targeting of signaling molecules to specific subcellular locations. We have identified a family with XLA whose affected members have a point mutation (g-->a) at the 5' splice site of intron 8, resulting in the skipping of coding exon 8 and loss of 21 amino acids forming the COOH-terminal portion of the BTK SH3 domain. The study of three generations within this kinship, using restriction fragment length polymorphism and DNA analysis, allowed identification of the mutant X chromosome responsible for XLA and the carrier status in this family. BTK mRNA was present in normal amounts in Epstein-Barr virus-induced B lymphoblastoid cell lines established from affected family members. Although the SH3 deletion did not alter BTK protein stability and kinase activity of the truncated BTK protein was normal, the affected patients nevertheless have a severe B cell defect characteristic for XLA. The mutant protein was modeled using the normal BTK SH3 domain. The deletion results in loss of two COOH-terminal beta strands containing several residues critical for the formation of the putative SH3 ligand-binding pocket. We predict that, as a result, one or more crucial SH3 binding proteins fail to interact with BTK, interrupting the cytoplasmic signal transduction process required for B cell differentiation

Homocysteine, folic acid and vitamin B12 levels in serum of epileptic children

The relationship between increased homocysteine (Hcy) level and epileptic seizure remains controversial in human, despite a growing evidence of the pro-convulsive effect of the hyperhomocysteinemia (HHcy) observed in the animal studies. The mechanism of this association with epileptogenesis has not been clearly understood, although there is emerging evidence to support the unfavorable effects of some anti-epileptic drugs (AEDs) on the plasma homocysteine (Hcy) concentrations. The aim of this study was to uncover the relationship between the levels of homocysteine (Hcy), the cofactors involved in its metabolism as folic acid and vitamin B12 and anti-epileptic drugs (AEDs) in epileptic patients. Serum level of homocysteine (Hcy), folic acid and vitamin B12 was measured in 60 patients with idiopathic epilepsy; and its level was compared to 30 healthy children serving as control group. No significant difference was found regarding the plasma homocysteine (Hcy) levels between patients (both receiving anti-epileptics and non anti-epileptic drug users) and controls. Epileptic patients on polytherapy showed higher mean serum levels of homocysteine (Hcy) and lower mean serum levels of folic acid compared to those on monotherapy. However, the mean serum levels of homocysteine (Hcy), vitamin B12 and folic acid showed non significant differences between patients using valproic acid (VPA) or carbamazepine (CBZ). Duration of AED therapy showed a significant positive correlation with mean serum levels of homocysteine (Hcy) and a significant negative correlation with mean serum levels of folic acid. To conclude; AEDs upset the homeostatic balance of homocysteine (Hcy) and its cofactors and cause abnormalities in their serum levels.Keywords: Homocysteine; Epilepsy; Folic acid; Vitamin B12; Anti-epileptic dru

Dietary elimination of children with food protein induced gastrointestinal allergy – micronutrient adequacy with and without a hypoallergenic formula?

Background: The cornerstone for management of Food protein-induced gastrointestinal allergy (FPGIA) is dietary exclusion; however the micronutrient intake of this population has been poorly studied. We set out to determine the dietary intake of children on an elimination diet for this food allergy and hypothesised that the type of elimination diet and the presence of a hypoallergenic formula (HF) significantly impacts on micronutrient intake. Method: A prospective observational study was conducted on children diagnosed with FPIGA on an exclusion diet who completed a 3 day semi-quantitative food diary 4 weeks after commencing the diet. Nutritional intake where HF was used was compared to those without HF, with or without a vitamin and mineral supplement (VMS). Results: One-hundred-and-five food diaries were included in the data analysis: 70 boys (66.7%) with median age of 21.8 months [IQR: 10 - 67.7]. Fifty-three children (50.5%) consumed a HF and the volume of consumption was correlated to micronutrient intake. Significantly (p <0.05) more children reached their micronutrient requirements if a HF was consumed. In those without a HF, some continued not to achieve requirements in particular for vitamin D and zinc, in spite of VMS. Conclusion: This study points towards the important micronutrient contribution of a HF in children with FPIGA. Children, who are not on a HF and without a VMS, are at increased risk of low intakes in particular vitamin D and zinc. Further studies need to be performed, to assess whether dietary intake translates into actual biological deficiencies

Global expansion of Vibrio parahaemolyticus threatens the seafood industry: Perspective on controlling its biofilm formation

As global warming increases the geographical range and frequency of Vibrio parahaemolyticus infections, its formation of biofilms providing bacteria greater resistance to stress and contributing to the persistence of pathogens, is threatening the seafood industry. V. parahaemolyticus has a number of advantages leading to biofilm formation. This study reviews recent advances in understanding V. parahaemolyticus biofilm formation on biotic and abiotic surfaces, discusses research gaps in the mechanism of biofilm formation and examines promising biofilm control strategies to overcome current limitations of chemical disinfectant. This information will deepen our understanding of V. parahaemolyticus biofilm formation, as well as help design and optimize V. parahaemolyticus biofilm control strategies for the seafood industry

Schistosoma haematobium infection levels determine the effect of praziquantel treatment on anti-schistosome and anti-mite antibodies

Field studies show an association between schistosome infection and atopy, but the effects of anti-helminthic treatment on this association have not yet been investigated in human populations with different schistosome endemicity levels. This study aimed to compare the effects of anti-helminthic treatment on responses directed against the house dust mite Dermatophagoides pteronyssinus (Derp1) and Schistosoma haematobium in Zimbabwean populations living in high and low schistosome infection areas. Derp1- and schistosome-specific IgE and IgG4 antibodies were quantified by ELISA before and 6 weeks after anti-helminthic treatment. Following treatment, there were changes in the immune responses, which varied with place of residence. After allowing for the effects of sex, age and baseline infection intensity, there was no significant treatment effect on the change in anti-schistosome IgE and IgG4 in the high infection area. However, the anti-schistosome IgE/IgG4 ratio increased significantly, while anti-Derp1 IgE responses decreased as a result of treatment. In the low infection area, treatment resulted in a significant increase in anti-worm IgE levels, but there was no significant treatment effect on anti-schistosome or anti-Derp1 IgE/IgG4 ratios. Thus, the study shows that the level of schistosome endemicity affects the host responses to schistosome and mite antigens following anti-helminthic treatment

Whole grain foods and health - A Scandinavian perspective

The food-based dietary guidelines in the Scandinavian countries that recommend an intake of minimum 75 g whole grain per 10 MJ (2,388 kcal) per day are mainly derived from prospective cohort studies where quantitative but little qualitative details are available on whole grain products. The objective of the current paper is to clarify possible differences in nutritional and health effects of the types of whole grain grown and consumed in the Scandinavian countries. A further objective is to substantiate how processing may influence the nutritional value and potential health effects of different whole grains and whole grain foods. The most commonly consumed whole grain cereals in the Scandinavian countries are wheat, rye, and oats with a considerable inter-country variation in the consumption patterns and with barley constituting only a minor role. The chemical composition of these different whole grains and thus the whole grain products consumed vary considerably with regard to the content of macro- and micronutrients and bioactive components. A considerable amount of scientific substantiation shows that processing methods of the whole grains are important for the physiological and health effects of the final whole grain products. Future research should consider the specific properties of each cereal and its processing methods to further identify the uniqueness and health potentials of whole grain products. This would enable the authorities to provide more specific food-based dietary guidelines in relation to whole grain to the benefit of both the food industry and the consumer

A ‘quiet revolution’? The impact of Training Schools on initial teacher training partnerships

This paper discusses the impact on initial teacher training of a new policy initiative in England: the introduction of Training Schools. First, the Training School project is set in context by exploring the evolution of a partnership approach to initial teacher training in England. Ways in which Training Schools represent a break with established practice are considered together with their implications for the dominant mode of partnership led by higher education institutions (HEIs). The capacity of Training Schools to achieve their own policy objectives is examined, especially their efficacy as a strategy for managing innovation and the dissemination of innovation. The paper ends by focusing on a particular Training School project which has adopted an unusual approach to its work and enquires whether this alternative approach could offer a more profitable way forward. During the course of the paper, five different models of partnership are considered: collaborative, complementary, HEI-led, school-led and partnership within a partnership

Potential for Inhalation Exposure to Engineered Nanoparticles from Nanotechnology-Based Cosmetic Powders

Background: The market of nanotechnology-based consumer products is rapidly expanding, and the lack of scientific evidence describing the accompanying exposure and health risks stalls the discussion regarding its guidance and regulation

Representation of women's health in general medical versus women's health specialty journals: a content analysis

BACKGROUND: Women's health, traditionally defined, emphasises reproductive and maternal conditions without consideration of social contexts. Advocates urge a broader conceptualisation. The medical literature influences the definitions and delivery of women's health care. We compared how women's health was represented in leading general medical (GM) versus women's health specialty (WS) journals. METHODS: Original investigations published between January 1 – June 30, 1999 in leading GM (n = 514) and WS (n = 82) journals were compared. Data were collected from 99 GM and 82 WS articles on women's health. Independent reviewers conducted content analyses of sample characteristics, study design, and health topic. Each article was classified as "Traditional" (e.g. menstruation, breast cancer), "Non-traditional" (e.g. abuse, osteoporosis), or "Both." RESULTS: Of the GM articles, 53 (53.5%) focused solely on a traditional women's health topic; half were reproductive and half female cancers. In contrast, 22 (26.8%) WS articles were traditionally focused. A non-traditional topic was the sole focus of 27 (27.3%) GM articles versus 34 (41.5%) WS articles. One-fifth of GM and one-third of WS articles addressed both. RCTs dominated the GM articles, while 40% of WS articles used qualitative or mixed study designs. Leading sources of women's death and disability were not well covered in either type of journal. CONCLUSIONS: Most GM articles drew on a narrow definition of women's health. WS journals provided more balanced coverage, addressing social concerns in addition to "navel-to-knees" women's health. Since GM journals have wide impact, editorial decisions and peer review processes should promote a broader conceptualisation of women's health