Association between the age of solid food introduction and eczema: A systematic review and a meta-analysis.

INTRODUCTION: Eczema is a common childhood ailment responsible for a considerable disease burden. Both timing of introduction to solid food and allergenic food are believed to be related to childhood eczema. Despite the growing body of evidence, the relationship between timing of any solid food introduction (allergenic and/or non-allergenic) and development of eczema has not previously been systematically reviewed. METHODS: PubMed and EMBASE databases were searched using food and eczema terms. Two authors selected papers according to the inclusion criteria and extracted information on study characteristics and measures of association. Meta-analyses were performed after grouping studies according to the age and type of exposure. RESULTS: A total of 17 papers met the inclusion criteria, reporting results from 16 study populations. Of these, 11 were cohort studies, 2 case-controls, 1 cross-sectional study and 2 randomized controlled trials. Limited meta-analyses were performed due to heterogeneity between studies. Timing of solid food introduction was not associated with eczema. One randomized controlled trial provided weak evidence of an association between early allergenic (around 4 months) food introduction and reduced risk of eczema. CONCLUSIONS: The available evidence is currently insufficient to determine whether the timing of introduction of any solid food influences the risk of eczema.

Exposure to 'farming' and objective markers of atopy: a systematic review and meta-analysis.

There is growing interest in the 'farm effect' on the spectrum of allergy. Evidence concerning the farm effect on asthma, eczema, and allergic rhinitis has been systematically synthesized, but without a specific focus on objective markers of sensitization. This focus is important, as farm exposures may be related to allergy but not to non-allergic phenotypes of disease. We aimed to systematically review and meta-analyse literature that has investigated associations between farm exposure at any age and objective measures of atopy, that is serum IgE or skin prick tests results. Using predefined inclusion and exclusion criteria, we identified 29 articles for review. IgE levels were measured in either childhood or adulthood by eighteen studies, while skin prick testing was performed in sixteen studies. Newcastle-Ottawa Scale quality assessments indicated that the majority of these studies demonstrated a representative sample of selected participants. Due to significant heterogeneity in study measures and methodology between studies, only few were meta-analysed. This meta-analysis showed a significant protective effect of farm exposure before 1 year of life on allergic sensitization (OR = 0.60 [0.52-0.70]). Farm exposure during childhood was also associated with a reduced risk of sensitization to cat or timothy (OR = 0.60 [0.51-0.70]; OR=0.46 [0.41-0.51]). Studies investigating the effect of farm exposure in adult life could not be meta-analysed, and their results were inconsistent. Insufficient studies investigated food sensitization as an outcome to allow synthesis. The majority of studies included in this review investigated childhood farm exposure, finding evidence to support a protective childhood 'farm effect' against subsequent atopy. There is inconsistent evidence on the association between farm exposure in adulthood and allergic sensitization. Further studies are needed to tease out the exact exposures and timing associated with farming environments that protect against allergic disease.

Atopic dermatitis and the atopic march revisited.

Atopic dermatitis (AD) has become a significant public health problem because of increasing prevalence, together with increasing evidence that it may progress to other allergic phenotypes. While it is now acknowledged that AD commonly precedes other allergic diseases, a link termed 'the atopic march', debate continues as to whether this represents a causal relationship. An alternative hypothesis is that this association may be related to confounding by familial factors or phenotypes that comanifest, such as early-life wheeze and sensitization. However, there is increasing evidence from longitudinal studies suggesting that the association between AD and other allergies is independent of confounding by comanifest allergic phenotypes. The hypotheses on plausible biological mechanisms for the atopic march focus on defective skin barrier function and overexpression of inflammatory mediators released by the skin affected by AD (including thymic stromal lymphopoietin). Both human and animal studies have provided evidence supporting these potential biological mechanisms. Evidence from prevention trials is now critical to establishing a causal nature of the atopic march. An emerging area of research is investigation into environmental modifiers of the atopic march. Such information will assist in identifying secondary prevention strategies to arrest the atopic march. Despite much research into the aetiology of allergies, little progress has been made in identifying effective strategies to reduce the burden of allergic conditions. In this context, the atopic march remains a promising area of investigation.

CD14 polymorphisms, microbial exposure and allergic diseases: a systematic review of gene-environment interactions.

Asthma and allergy may develop as a result of interactions between environmental factors and the genetic characteristics of an individual. This review aims to summarize the available evidence for, and potential effects of, an interaction between polymorphisms of the CD14 gene and exposure to microbes on the risk of asthma and allergic diseases. We searched PubMed, MEDLINE and Global Health databases, finding 12 articles which met inclusion criteria. Most studies reported a significant interaction between CD14 polymorphisms and microbial exposure. When stratified by age at microbial exposure (early life vs adult life), there was evidence of a protective effect of gene-environment interaction against atopy in children, but not adults. We also found different effects of interaction depending on the type of microbial exposures. There was no strong evidence for asthma and eczema. Future studies should consider a three-way interaction between CD14 gene polymorphisms, microbial exposures and the age of exposure.

Adult serum cytokine concentrations and the persistence of asthma.

BACKGROUND: Cytokines play a pivotal role in regulating the development and persistence of the inflammatory process in asthma. Our aim was to investigate whether asthma persistence or remission is associated with a specific cytokine profile. METHODS: The Tasmanian Longitudinal Health Study followed participants from 7 to 44 years of age. Serum concentrations of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10 and tumor necrosis factor-alpha (TNF-α) were measured at age 44 years. Participants were categorized into five phenotypes (early-onset noncurrent asthma, early-onset current asthma, late-onset noncurrent asthma and late-onset current asthma). Those who had never had asthma formed the reference group. Multivariable linear regression was used to compare serum cytokine concentrations between each phenotype and the reference group. RESULTS: IL-10 concentrations were significantly lower in serum from the early-onset current asthma group than in the reference group (ratio of geometric means 0.58; 95% confidence interval 0.33-0.99; p = 0.048). IL-6 concentrations for the late-onset remitted group were also significantly lower than in the reference group (p = 0.009). The TNF-α concentrations were significantly lower for both early-and late-onset remitted asthma phenotypes when compared with the reference group. No associations were detected between serum concentrations of IL-4, IL-5 or IL-8 and these specific longitudinal asthma phenotypes. CONCLUSION: Our findings suggest a possible role for deficient IL-10 responses in the persistence of early-onset asthma. Lower IL-6 and TNF-α concentrations in serum from those with remitted asthma suggest that these proinflammatory cytokines may be actively suppressed during asthma remission.

Effect of using stencil masks made by focused ion beam milling on permalloy (Ni81Fe19) nanostructures.

Focused ion beam (FIB) milling is a common fabrication technique to make nanostencil masks which has the unintended consequence of gallium ion implantation surrounding milled features in silicon nitride membranes. We observe major changes in film structure, chemical composition, and magnetic behaviour of permalloy nanostructures deposited by electron beam evaporation using silicon nitride stencil masks made by a FIB as compared to stencil masks made by regular lithography techniques. We characterize the stenciled structures and both types of masks using transmission electron microscopy, electron energy loss spectroscopy, energy dispersive x-ray spectroscopy, magnetic force microscopy and kelvin probe force microscopy. All these techniques demonstrate distinct differences at a length scale of a 1-100 nm for the structures made using stencil mask fabricated using a FIB. The origin of these differences seems to be related to the presence of implanted ions, a detailed understanding of the mechanism however remains to be developed.

Partially transformed, anchorage-independent human diploid fibroblasts result from overexpression of the c-sis oncogene: mitogenic activity of an apparent monomeric platelet-derived growth factor 2 species.

A human c-sis cDNA in an expression vector was introduced into human diploid fibroblasts by transfection or electroporation. Fibroblast clones showing an aberrant, densely packed colony morphology were isolated and found to overexpress a 3.6-kilobase sis mRNA species and associated immunoprecipitable platelet-derived growth factor (PDGF) 2 proteins. Parallel analyses in cell clones of sis mRNA expression and colony formation in agar indicated that, above a threshold, a linear, positive correlation existed between sis overexpression and acquired anchorage independence. The sis-overexpressing cells formed transient, regressing tumor nodules when injected into nude mice, consistent with the finite life span which they retained. Protein products generated from the transfected c-sis construct in two overexpressing clones were immunoprecipitated with anti-human PDGF antibodies. One clone contained an apparent PDGF dimer of 21 kilodaltons; the second clone contained only an apparent PDGF monomer of 12 kilodaltons, which was shown to account for all of the mitogenic activity present in the cells, essentially all of which was concentrated in the membrane fraction. The results demonstrate a clear link between sis overexpression and acquisition of a partially transformed, anchorage-independent phenotype, and when combined with previous observations of sis overexpression in human tumors, clearly implicate sis overexpression as a genetic mechanism which contributes to human cell transformation.

Changes of the cortex proteome and Apolipoprotein E in transgenic mouse models of Alzheimer's Disease.

Transgenic mice carrying human Amyloid Precursor Protein mutations present amyloid plaque deposition in the brain upon aging. In this study, we characterized the changes of cortex proteome and endogenous Apolipoprotein E in these mice. Differential analysis of two-dimensional electrophoresis images revealed spots altered upon aging, transgene addition and plaque deposition. Alpha-synuclein and cytochrome oxidase polypeptide Va were up-regulated in transgenic mice. Upon aging, expression of ATP synthase alpha, alpha enolase, UMP-CMP kinase, and dihydropyrimidinase like-2 protein was modified. These proteins and their modification probably play a role in the amyloid aggregate formation in these mice.

Mutation at separate gene loci in Salmonella typhimurium TA100 related to DNA nucleotide modification by stereoisomeric benzo(a)pyrene 7,8-diol-9,10-epoxides.

Suspensions of Salmonella typhimurium TA100 or TA1535 cells were exposed to pure enantiomeric forms or racemic mixtures of 3H-labeled benzo(a)pyrene anti- or syn-7,8-dihydrodiol-9,10-epoxide. Diol-epoxide-induced cytotoxicity and mutation frequencies at the hisG and gpt loci were determined. Hydrolysates of diol-epoxide-modified bacterial DNA were also examined by high-performance liquid chromatography and the primary structure and level of diol-epoxide-nucleoside adduct species were related to the observed frequencies of reverse mutations at the mutant hisG46 codon (histidine prototrophy) or forward mutations at the gpt locus (8-azaguanine resistance). Significant differences in mutagenic efficiency (i.e., mutation frequency per mol DNA adduct) were observed for the different enantiomeric diol-epoxides (-anti = +/- syn much greater than, + anti) and the mutagenic efficiencies were the same at both loci. The combined results of the mutation and adduct characterizations suggest that there are basic differences in the structural configuration of each adduct species which are recognized during errant DNA repair and as a result lead to base changes at a frequency which is relatable to the configuration of the original adduct lesion.

Nanoscale Structure, Dynamics, and Aging Behavior of Metallic Glass Thin Films.

Scanning tunnelling microscopy observations resolve the structure and dynamics of metallic glass Cu100-xHfx films and demonstrate scanning tunnelling microscopy control of aging at a metallic glass surface. Surface clusters exhibit heterogeneous hopping dynamics. Low Hf concentration films feature an aged surface of larger, slower clusters. Argon ion-sputtering destroys the aged configuration, yielding a surface in constant fluctuation. Scanning tunnelling microscopy can locally restore the relaxed state, allowing for nanoscale lithographic definition of aged sections.

Torque-mixing magnetic resonance spectroscopy.

A universal, torque-mixing method for magnetic resonance spectroscopy is presented. In analogy to resonance detection by magnetic induction, the transverse component of a precessing dipole moment can be measured in sensitive broadband spectroscopy, here using a resonant mechanical torque sensor. Unlike induction, the torque amplitude allows equilibrium magnetic properties to be monitored simultaneously with the spin dynamics. Comprehensive electron spin resonance spectra of a single-crystal, mesoscopic yttrium iron garnet disk at room temperature reveal assisted switching between magnetization states and mode-dependent spin resonance interactions with nanoscale surface imperfections. The rich detail allows analysis of even complex three-dimensional spin textures. The flexibility of microelectromechanical and optomechanical devices combined with broad generality and capabilities of torque-mixing magnetic resonance spectroscopy offers great opportunities for development of integrated devices.

Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease.

Using a combination of iterative structure-based design and an analysis of oral pharmacokinetics and antiviral activity, AG1343 (Viracept, nelfinavir mesylate), a nonpeptidic inhibitor of HIV-1 protease, was identified. AG1343 is a potent enzyme inhibitor (Ki = 2 nM) and antiviral agent (HIV-1 ED50 = 14 nM). An X-ray cocrystal structure of the enzyme-AG1343 complex reveals how the novel thiophenyl ether and phenol-amide substituents of the inhibitor interact with the S1 and S2 subsites of HIV-1 protease, respectively. In vivo studies indicate that AG1343 is well absorbed orally in a variety of species and possesses favorable pharmacokinetic properties in humans. AG1343 (Viracept) has recently been approved for marketing for the treatment of AIDS.

Pharmacological management of recurrent oral mucosal ulceration.

A number of diseases can cause recurrent intraoral ulceration. This review focuses principally on drug management of intraoral ulceration associated with local and systemic conditions most likely to be observed on an outpatient basis by the general practitioner. These consist of recurrent aphthous stomatitis, erosive lichen planus, benign mucous membrane pemphigoid (BMMP), erythema multiforme. Behçet's disease, allergic stomatitis and infection. Information is provided on a spectrum of medication found useful in ulcer management, including topical antimicrobial and antifungal agents, topical and systemic corticosteroids, topical and systemic analgesics, and systemic immunosuppressive and anxiolytic drugs, plus details of dosage, important adverse reactions and interactions. A treatment guide for management of recurrent aphthae is presented. The reader is presumed to be familiar with differential diagnosis and the importance of establishing an accurate impression before starting drug therapy.

Benzo[a]pyrene diol-epoxides: different mutagenic efficiency in human and bacterial cells.

Monolayer cultures of diploid human fibroblasts and suspensions of S. typhimurium TA100 cells were treated with [3H]-labelled enantiomeric forms of benzo[a]pyrene anti and syn 7,8-dihydrodiol 9,10-epoxides. In both cell types, all of the enantiomers induced the formation of mutant 6-thioguanine (human) or 8-azaguanine-(bacterial)resistant cells. Diol-epoxide-modified nucleosides from human and from bacterial DNA hydrolysates were characterized by HPLC and showed essentially the same adduct species for human and bacterial cells treated with the same enantiomers. There were substantial differences, however, in the efficiency with which structurally-different adduct species were converted to mutant genotypes. In human cells, the mutagenic efficiency (mutation frequency/unit modified DNA) of the respective adduct species (+ anti much greater than -anti = +/- syn) at the hprt locus was exactly the opposite of that seen at a similar gene locus (gpt) in TA100 (-anti = +/- syn greater than + anti). The results suggest that the structural configuration of adducts in genomic DNA is important in determining whether a mutant genotype will result, and likewise, that there are differences in specificity between the human and bacterial systems which process these adduct lesions.

A comparison of TMD patients with or without prior motor vehicle accident involvement: treatment and outcomes.

The influence of previous trauma in the management of patients with temporomandibular disorders (TMD) is controversial. The objectives of this study were to compare treatment regimens and outcomes in motor vehicle accident trauma-related versus nontrauma-related TMD patients. Files of 50 trauma and 50 matched nontrauma TMD patients were reviewed. Information concerning treatment received, progress of symptoms with treatment, and findings from the final examination were recorded. As a whole group, posttraumatic TMD patients tended to receive more types of treatment (P < .0001), have more medications prescribed (including analgesics, P < .001; nonsteroidal anti-inflammatory drugs, P = .001; muscle relaxants, P = .001; and tricyclic antidepressants, P < .001), have more oral medicine clinic visits (P = .07) over a longer period of time (P = .06), and have a poorer treatment outcome (P < .001) as compared to the nontrauma group. When the patients were separated into TMD diagnostic classification subsets, only some of these differences between trauma and nontrauma patients were seen, but the subset group sizes were small and only a few of the groups could be compared. There did not seem to be a significant effect from settling insurance claims prior to the last clinic visit. Trauma may be an important prognostic factor in the management of some TMD patients.

Temporomandibular disorders, headaches, and neck pain following motor vehicle accidents and the effect of litigation: review of the literature.

A literature review concerning the relationships between motor vehicle accidents and temporomandibular disorders, whiplash, headache, neck pain, and litigation was undertaken. The review shows that many patients recover or resume work prior to settlement, but most unsuccessfully treated patients do not generally recover following the settlement of legal claims; the postinjury problems are not strictly psychologic. Litigating patients and nonlitigating patients are often not dramatically different in most important regards (including pain and return to work), with litigating patients deserving the same treatment as other patients with chronic pain. It was found that postinjury neck symptoms and headaches can be persistent. Employment appears to be a better predictor of long-term outcome than compensation and litigation. In addition, limited consensus is available concerning prognostic factors. Patients with postinjury temporomandibular disorders tend to respond less well to treatment than do noninjury patients with temporomandibular disorders, as do litigating compared to nonlitigating temporomandibular disorders patients, but a cause and effect relationship is not known. The incidence of temporomandibular disorders following motor vehicle accidents may not be as high as has been claimed in whiplash cases. More research is required in the area of temporomandibular disorders, motor vehicle accidents, and litigation.

A comparison of TMD patients with or without prior motor vehicle accident involvement: initial signs, symptoms, and diagnostic characteristics.

The role of trauma in the etiology of temporomandibular disorders (TMD) is controversial. The objectives of this study were to compare presenting signs, symptoms, and diagnoses in patients who had motor vehicle accident trauma-related TMD to patients who had nontrauma-related TMD. Files of 50 trauma and 50 matched nontrauma TMD patients were reviewed. Information concerning presenting pain, temporomandibular joint (TMJ) and related symptoms, examination findings, and diagnoses was recorded. Posttraumatic TMD patients reported higher facial (P = .006) and headache (P = .0001) pain ratings, neck symptom frequency (P < .01), ear-related symptoms (P = .02), sleep disturbance (P < .001), and occupational and avocational disability frequencies (P < .0001). They had greater masticatory muscle (P < .001), neck muscle (P < .001), and TMJ tenderness (P = .01) scores and myofascial pain (P = .006) and arthralgia/capsulitis (P = .008) diagnoses. The nontrauma group had more subjective (P = .02) and objective (P = .05) TMJ crepitus and higher self-reports of parafunctional jaw habits (P = .05). Trauma may be an important etiologic factor for some TMD patients.

Effect of impact and injury characteristics on post-motor vehicle accident temporomandibular disorders.

OBJECTIVES: The objective of this study was to assess the potential effects of motor vehicle accident impact and injury characteristics on post-motor vehicle accident temporomandibular disorders in terms of presenting signs and symptoms, diagnoses, treatment regimens, and outcomes. STUDY DESIGN: A retrospective chart review of 50 patients with post-motor vehicle accident temporomandibular disorders from a private oral medicine practice was undertaken. Various demographic data and data related to temporomandibular disorders and motor vehicle accident impact and injury characteristics were collected. Chi-square and Fisher exact tests and multiple regression analyses were performed. RESULTS: Patients involved in front-end collisions or motor vehicle accidents resulting in severe vehicle damage reported more direct orofacial injury. However, those in rear-end collisions or accidents resulting in minimal vehicle damage required more treatment. Direct head or orofacial injury was therefore not a prognostic indicator. From multiple regression analyses, indicators of a poorer prognosis were minimal vehicle damage, lack of headrest use, driver position, and settlement of insurance claim. CONCLUSIONS: In this patients group several prognostic indicators for patients with post-motor vehicle accident temporomandibular disorders were identified; these indicators may influence the management approach for this patient population.

Litigation and post-traumatic TMD: how patients report treatment outcome.

Ongoing litigation may affect treatment response in patients with trauma-induced TMD. A survey of 100 patients underscores the need for comprehensive psychosocial and behavioral assessment, including evaluation of litigation status in these patients.

Orofacial pain of psychogenic origin: current concepts and classification.

A description and attempt to classify the newly revised DSM-III and IASP classification schemes and those persistent orofacial pain syndromes that are commonly considered to be significantly associated with psychological or psychosocial factors, either as primary causes or as factors contributing to the maintenance of the chronic pain state are presented. The classification schemes include the DSM-III-R of the American Psychiatric Association and the new IASP taxonomy system, are the two systems currently available for classifying chronic orofacial pain states that are often considered to represent psychogenic pain conditions.