Brain charts for the human lifespan.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Does personalized melanoma genomic risk information trigger conversations about skin cancer prevention and skin examination with family, friends and health professionals?

BACKGROUND: Receiving information about genomic risk of melanoma might trigger conversations about skin cancer prevention and skin examinations. OBJECTIVES: To explore conversations prompted by receiving personalized genomic risk of melanoma with family, friends and health professionals. METHODS: We used a mixed-methods approach. Participants without a personal history and unselected for a family history of melanoma (n = 103, aged 21-69 years, 53% women) completed questionnaires 3 months after receiving a personalized melanoma genomic risk assessment. Semistructured interviews were undertaken with 30 participants in high, average and low genomic risk categories, and data were analysed thematically. RESULTS: From the questionnaires, 74% of participants communicated their genomic risk information with family, and 49% with friends. Communication with a health professional differed by risk level: 41%, 16% and 12% for high, average and low risk, respectively (P = 0·01). Qualitative analysis showed that perceived 'shared risk' and perceived interest of family and friends were motivations for discussing risk or prevention behaviours. The information prompted conversations with family and health professionals about sun protection and skin checks, and general conversations about melanoma risk with friends. Reasons for not discussing with family included existing personal or family health concerns, or existing high levels of sun protection behaviour among family members. CONCLUSIONS: Personalized melanoma genomic risk information can prompt risk-appropriate discussions about skin cancer prevention and skin examinations with family and health professionals. Sharing this information with others might increase its impact on melanoma prevention and skin examination behaviours, and this process could be used to encourage healthy behaviour change within families.

'Start the conversation': the New South Wales (Australia) family health history campaign.

BACKGROUND: Evidence that family health history (FHH) informs recommendations for appropriate early detection strategies used for the prevention of many health conditions underscores the importance of optimizing a patient's knowledge of his/her personal FHH. For some conditions, FHH also underpins identifying those at potentially high risk for whom genetic testing may be possible and suitable to further inform the advice. The Family Health History Campaign 'Start the Conversation' was conducted in New South Wales (Australia) in August 2006 as a small state-wide media campaign with the aim of encouraging individuals to discuss and gather their FHH information about several conditions and report it to their doctor. Campaign development included consultations with consumers and primary care practitioners (general practitioners - GPs), development of campaign resources, and establishment of partnerships. METHODS: Evaluation methodologies included community poll surveys pre- and post-campaign, a GP mail survey, and website usage analysis. RESULTS: While only 112/403 of the polled community reported hearing about the campaign in the media, 48% of those men and women were encouraged to start the conversation with their families. Limited findings from the GP survey respondents suggested they were engaged, made aware of the potential lack of patient knowledge about FHH and generated referral for several high-risk patients. CONCLUSION: Campaigns that use the media to encourage the community to take action and also engage the GPs can create a supportive environment that has the potential to increase the accuracy with reporting of FHH to maximize benefit for early detection and prevention.

Monitoring growth in asthmatic children treated with high dose inhaled glucocorticoids does not predict adrenal suppression.

AIMS: To determine whether routine outpatient monitoring of growth predicts adrenal suppression in prepubertal children treated with high dose inhaled glucocorticoid. METHODS: Observational study of 35 prepubertal children (aged 4-10 years) treated with at least 1000 microg/day of inhaled budesonide or equivalent potency glucocorticoid for at least six months. Main outcome measures were: changes in HtSDS over 6 and 12 month periods preceding adrenal function testing, and increment and peak cortisol after stimulation by low dose tetracosactrin test. Adrenal suppression was defined as a peak cortisol < or =500 nmol/l. RESULTS: The areas under the receiver operator characteristic curves for a decrease in HtSDS as a predictor of adrenal insufficiency 6 and 12 months prior to adrenal testing were 0.50 (SE 0.10) and 0.59 (SE 0.10). Prediction values of an HtSDS change of -0.5 for adrenal insufficiency at 12 months prior to testing were: sensitivity 13%, specificity 95%, and positive likelihood ratio of 2.4. Peak cortisol reached correlated poorly with change in HtSDS (rho = 0.23, p = 0.19 at 6 months; rho = 0.33, p = 0.06 at 12 months). CONCLUSIONS: Monitoring growth does not enable prediction of which children treated with high dose inhaled glucocorticoids are at risk of potentially serious adrenal suppression. Both growth and adrenal function should be monitored in patients on high dose inhaled glucocorticoids. Further research is required to determine the optimal frequency of monitoring adrenal function.

Hypopituitarism following cerebral oedema with diabetic ketoacidosis.

Clinical evidence of cerebral oedema occurs in approximately 1% of diabetic ketoacidosis episodes. Mortality from this serious complication is falling, but little is known of long term outcome. We describe hypopituitarism and executive dysfunction developing two years after cerebral oedema complicating diabetic ketoacidosis in a 12 year old with type 1 diabetes.

Hypoglycemia due to adrenal suppression secondary to high-dose nebulized corticosteroid.

High-dose inhaled corticosteroids, greater than 400 mcg per day of beclomethasone dipropionate or equivalent, can cause adrenal insufficiency, but a hypoglycemic crisis has not been reported with the use of nebulized corticosteroids. We describe a 21-month-old asthmatic boy who had a hypoglycemic seizure during a proven acute adrenal crisis secondary to high-dose nebulized budesonide treatment.

Automated mass analysis of low-molecular-mass bacterial proteome by liquid chromatography-electrospray ionization mass spectrometry.

Due to the presence of a large number of proteins in cell extracts, ion chromatograms of cell extracts obtained by electrospray ionization mass spectrometry (ESI-MS) can be quite complicated. It is found that the elevated baseline in an ion chromatogram contains many protein signals. One deficiency of current commercially available LC-ESI-MS data interpretation software is found to be the lack of functional operation that allows automated mass spectral integration and interpretation over signals hidden in the baseline. This current limitation can be overcome by a technique that involves the introduction of artificial pulses to an ion chromatogram by removing the solvent mixer in the HPLC pump. These artificial pulses are treated as chromatographic peaks by the software, thereby allowing automated spectral integration over the duration of a pulse. The reliability of mass analysis from the integrated spectra is shown to be dependent on spectral interpretation parameters such as mass spectral baseline threshold. The application of this method is demonstrated for rapid detection and mass analysis of low-molecular-mass proteins from cell extracts of Escherichia coli or Bacillus globigii.

Caterpillar dermatitis.

A 3-year-old girl presented with recurrent urticarial eruptions presumed due to infestation of her garden with Euproctis edwardsi, Euproctis edwardsi, the mistletoe browntail moth is a variety of hairy caterpillar widely distributed in south-eastern Australia. They are often called 'woolly bears' by children. These caterpillars possess barbed hairs that fragment readily and are difficult to extract from the skin in one piece. Itching urticarial wheals and papular eruptions can follow contact with the caterpillars or their detached hairs. The hairlets may be identified by microscopy from skin scrapings and can be removed by tape stripping or with the aid of fine forceps. The skin lesions are treated symptomatically with calamine lotion, sodium bicarbonate solution and antihistamines. Infestation with Euproctis edwardsi can be minimized by removal of mistletoe from eucalyptus trees and by spraying affected areas with white oil or carbaryl 0.1%.

Growth and adrenal suppression in asthmatic children treated with high-dose fluticasone propionate.

BACKGROUND: Fluticasone propionate was introduced in 1993 in the UK as a potentially safer inhaled corticosteroid than those already in use. The efficacy and safety of fluticasone has been established at recommended doses of 200 micrograms/day, but not at higher doses that are often used. METHODS: Growth retardation was observed in six severely asthmatic children after introduction of high-dose fluticasone propionate treatment (dry powder). Assessment of cortisol response was by insulin-induced hypoglycaemia in three cases, by short tetracosactrin test in two, and by low-dose tetracosactrin and 24-hour urinary cortisol/creatinine ratio in one. FINDINGS: Six children with growth retardation noted after treatment with high-dose fluticasone propionate were found to have adrenal suppression. In one case the growth rate and cortisol response returned to normal 9 months after the fluticasone dose was reduced to 500 micrograms/day. INTERPRETATION: When high doses of fluticasone propionate are used, growth may be retarded and adrenal suppression may occur.

Coliforms in processed mango: significance and control.

The aims of this investigation were to enumerate coliforms in fresh mangoes, puree, cheeks, and cheeks-in-puree in order to determine the source of these organisms in the processed products, to determine methods for their control, and to identify coliforms isolated from cheeks-in-puree to determine whether they have any public health significance. Product from four processors was tested on two occasions. The retail packs of cheeks-in-puree having the highest coliform counts were those in which raw puree was added to the cheeks. Coliform counts in these samples ranged between 1.4 x 10(3) and 5.4 x 10(4) cfu/g. Pasteurisation reduced the coliform count of raw puree to < 5 cfu/g. Forty-seven percent of the 73 colonies, isolated as coliforms on the basis of their colony morphology on violet red bile agar, were identified as Klebsiella pneumoniae using the ATB 32E Identification System. Klebsiella strains were tested for growth at 10 degrees C, faecal coliform response, and fermentation of D-melizitose, to differentiate the three phenotypically similar strains, K. pneumoniae, K. terrigena and K planticola. Results indicated that 41% of K. pneumoniae isolates gave reactions typical of K. pneumoniae. A further 44% of strains gave an atypical reaction pattern for these tests and were designed 'psychrotrophic' K. pneumoniae. Klebsiella pneumoniae counts of between 2.1 x 10(3) and 4.9 x 10(4) cfu/g were predicted to occur in the retail packs of mango cheeks-in-puree produced by the processors who constituted this product with raw puree. In view of the opportunistic pathogenic nature of K. pneumoniae, its presence in these products is considered undesirable and steps, such as pasteurisation of puree, should be taken in order to inactivate it.

A comparative study of isolutrol versus benzoyl peroxide in the treatment of acne.

Isolutrol is the active principle isolated from aqueous tissue extracts of deep sea shark liver and gall-bladder. A previous study has demonstrated the ability of isolutrol to reduce hyperseborrhoea, which provides a rationale for its use in the treatment of acne. We have performed a double-blind clinical trial on 70 patients to evaluate the efficacy and skin tolerance of isolutrol 0.15 g/100 mL (Ketsugo) in the treatment of mild to moderate acne when compared with 5% benzoyl peroxide lotion. The results from this study showed that both isolutrol and benzoyl peroxide significantly improved patients' acne by reducing the number of inflamed lesions. Isolutrol did not significantly reduce the numbers of non-inflamed lesions whereas benzoyl peroxide did. Fewer side effects were experienced by patients treated with isolutrol when compared with benzoyl peroxide. These results indicate that isolutrol may be a useful adjunct in the treatment of acne, particularly in patients with inflamed lesions.

All-trans retinoic acid induces functional maturation of epidermal Langerhans cells and protects their accessory function from ultraviolet radiation.

Retinoids provide some protection against ultraviolet radiation-induced skin damage. We have previously shown that topical all-trans retinoic acid prevents ultraviolet light from reducing the density of epidermal Langerhans cells in the epidermis but does not inhibit the development of immunosuppression to a locally applied contact sensitizer. We therefore investigated the ability of all-trans retinoic acid to modulate Langerhans cell induction of allogeneic T-cell proliferation in the mixed epidermal cell lymphocyte reaction. Langerhans cells isolated from all-trans retinoic acid-treated mice induced an enhanced mixed epidermal cell lymphocyte reaction. This is similar to Langerhans cells cultured with granulocyte-macrophage colony stimulating factor. Retinoic acid treatment also enhanced the allogeneic cell-stimulating capability of Langerhans cells isolated from ultraviolet-irradiated mice. Langerhans cells from all-trans retinoic acid-treated, ultraviolet-irradiated mice which were "matured" by 3 days in culture induced a larger mixed epidermal cell lymphocyte reaction than mice treated with solvent and ultraviolet irradiation. Thus all-trans retinoic acid treatment of mice causes Langerhans cell maturation and inhibits ultraviolet light from reducing their density or impairing their allogeneic cell-stimulating capacity. However, these mice remained immunosuppressed upon application of a contact sensitizer to irradiated or unirradiated skin. It is thus likely that, whereas all-trans retinoic acid protects local Langerhans cell numbers and function, it does not inhibit the production of an ultraviolet radiation-induced photoproduct which causes immunosuppression.

Selection of monoclonal antibodies that bind and inhibit tissue-type plasminogen activator.

Three monoclonal antibodies raised against tissue-type plasminogen activator (t-PA) were selected for their ability to inhibit solid-phase bound t-PA. Each monoclonal antibody blocked the release of p-nitroaniline from H-D-Ile-Pro-Arg-pNA (S-2288). The first antibody 1D2 was a gamma 2b, kappa with KD = 8 x 10(-9) M, the second antibody 2B9 was a gamma 1, kappa with KD = 2 x 10(-9) M, and the third antibody 5A9 was a gamma 1,kappa with KD = 4 x 10(-10) M. In solution-phase format each antibody blocked the conversion of plasminogen to plasmin as judged by a plasmin assay and also inhibited t-PA-mediated lysis of plasma fibrin clot in plasma. The binding of each 125I-radiolabeled antibody to t-PA was inhibited by any one of the three antibodies, suggesting that they recognized a common epitope on t-PA which was absent on unfolded t-PA. We concluded these antibodies bind near t-PA active site since PPACK treatment lowered binding of two antibodies. We believe solid-phase chromogenic substrate assay may be a useful way to screen for antibodies directed against the active site of proteases.

Maxillary sinusitis from Pseudallescheria boydii. Efficacy of surgical therapy.

Pseudallescheria boydii is a ubiquitous mold of soil and is a frequent cause of mycetoma in the United States. Involvement of the sinuses is extremely rare. The necessity of medical and/or surgical management is largely unknown but appears to be dependent on variables of host defense mechanisms, as the fungus is relatively avirulent. Chronic maxillary sinusitis secondary to P boydii developed in a noncompromised woman. Evidence of erosion of the bony wall of the orbit was encountered at operation. Successful eradication of this infection was accomplished with surgical drainage alone.

Mechanism of monensin-induced hyperpolarization of neuroblastoma-glioma hybrid NG108-15.

Addition of the ionophore monensin to mouse neuroblastoma-rat glioma hybrid NG108-15 cells leads to a 20 to 30-mV increase in the electrical potential across the plasma membrane as shown by direct intracellular recording techniques and by distribution studies with the lipophilic cation [3H]-tetraphenylphosphonium+ (TPP+) [Lichtshtein, D., Kaback, H.R. & Blume, A.J. (1979) Proc. Natl. Acad. Sci. USA 76, 650-654]. The effect is not observed with cells suspended in high K+ medium, is dependent upon the presence of Na+ externally, and the concentration of monensin that induces half-maximal stimulation of TPP+ accumulation is approximately 1 microM. The ionophore also causes rapid influx of Na+, a transient increase in intracellular pH, and a decrease in extracellular pH, all of which are consistent with the known ability of monensin to catalyze the transmembrane exchange of H+ for Na+. Although ouabain has no immediate effect on the membrane potential, the cardiac glycoside completely blocks the increase in TPP+ accumulation observed in the presence of monensin. Thus, the hyperpolarizing effect of monensin is mediated apparently by an increase in intracellular Na+ that acts to stimulate the electrogenic activity of the Na+,K+-ATPase. Because monensin stimulates TPP+ accumulation in a number of other cultured cell lines in addition to NG108-15, the techniques described may be of general use for studying the Na+,K+ pump and its regulation in situ.