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Background: The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum. Methods. Here, we analysed sera from adults diagnosed with AS (males = 14, females = 16) and controls (males = 13, females = 16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MS§ssup§E§esup§). The main objective was to identify sex-specific serum protein changes associated with AS. Results: Multiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MS§ssup§E§esup§ profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls. Conclusion: Taken together, the serum multiplex immunoassay and shotgun LC- MS§ssup§E§esup§ profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of nov

Background: The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum. Methods: Here, we analysed sera from adults diagnosed with AS (males = 14, females = 16) and controls (males = 13, females = 16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MSE). The main objective was to identify sex-specific serum protein changes associated with AS. Results: Multiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MSE profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls. Conclusion: Taken together, the serum multiplex immunoassay and shotgun LC-MSE profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment approaches.

Objective: Although most national guidelines for the diagnosis and management of hypertension emphasize that the initiation and modification of blood pressure (BP)-lowering treatment should be related to absolute cardiovascular disease (CVD) risk, there is only limited information on how to incorporate ambulatory BP (ABP) monitoring into this framework. The objective of this initiative is to provide ABP equivalents for BP cut-points for treatment initiation and targets to be included into guidelines. Method(s): A critical analysis of the best available evidence from clinical trials and observational studies was undertaken to develop a new consensus statement for ABP monitoring. Result(s): ABP monitoring has an important place in defining abnormal patterns of BP, particularly white-coat hypertension (including in pregnancy), episodic hypertension, masked hypertension, labile BP and nocturnal or morning hypertension. This consensus statement provides a framework for appropriate inclusion of ABP equivalents for low, moderate and high CVD risk patients. The wider use of ABP monitoring, although justified, is limited by its availability and cost due to the lack of medical subsidy in Australia. However, cost-benefit analysis does suggest a cost-saving in reduced numbers of inappropriate antihypertensive treatments. Conclusion(s): Although clinic measurement of BP will continue to be useful for screening and management of suspected and true hypertension, ABP monitoring provides considerable added value toward accurate diagnosis and the provision of optimal care in uncomplicated hypertension, as well as for patients with moderate or severe CVD risk. © 2012 Wolters Kluwer Health Lippincott Williams & Wilkins.

Background: Sex is an important factor in the prevalence, incidence, progression, and response to treatment of many medical conditions, including autoimmune and cardiovascular diseases and psychiatric conditions. Identification of molecular differences between typical males and females can provide a valuable basis for exploring conditions differentially affected by sex. Methodology/Principal Findings: Using multiplexed immunoassays, we analyzed 174 serum molecules in 9 independent cohorts of typical individuals, comprising 196 males and 196 females. Sex differences in analyte levels were quantified using a meta-analysis approach and put into biological context using k-means to generate clusters of analytes with distinct biological functions. Natural sex differences were established in these analyte groups and these were applied to illustrate sexually dimorphic analyte expression in a cohort of 22 males and 22 females with Asperger syndrome. Reproducible sex differences were found in the levels of 77 analytes in serum of typical controls, and these comprised clusters of molecules enriched with distinct biological functions. Analytes involved in fatty acid oxidation/hormone regulation, immune cell growth and activation, and cell death were found at higher levels in females, and analytes involved in immune cell chemotaxis and other indistinct functions were higher in males. Comparison of these naturally occurring sex differences against a cohort of people with Asperger syndrome indicated that a cluster of analytes that had functions related to fatty acid oxidation/hormone regulation was associated with sex and the occurrenc

Objective: Although most national guidelines for the diagnosis and management of hypertension emphasize that the initiation and modification of blood pressure (BP)-lowering treatment should be related to absolute cardiovascular disease (CVD) risk, there is only limited information on how to incorporate ambulatory BP (ABP) monitoring into this framework. The objective of this initiative is to provide ABP equivalents for BP cut-points for treatment initiation and targets to be included into guidelines. Method(s): A critical analysis of the best available evidence from clinical trials and observational studies was undertaken to develop a new consensus statement for ABP monitoring. Result(s): ABP monitoring has an important place in defining abnormal patterns of BP, particularly white-coat hypertension (including in pregnancy), episodic hypertension, masked hypertension, labile BP and nocturnal or morning hypertension. This consensus statement provides a framework for appropriate inclusion of ABP equivalents for low, moderate and high CVD risk patients. The wider use of ABP monitoring, although justified, is limited by its availability and cost due to the lack of medical subsidy in Australia. However, cost-benefit analysis does suggest a cost-saving in reduced numbers of inappropriate antihypertensive treatments. Conclusion(s): Although clinic measurement of BP will continue to be useful for screening and management of suspected and true hypertension, ABP monitoring provides considerable added value toward accurate diagnosis and the provision of optimal care in uncomplicated hypertension, as well as for patients with moderate or severe CVD risk. © 2012 Wolters Kluwer Health Lippincott Williams & Wilkins.

Background: Sex is an important factor in the prevalence, incidence, progression, and response to treatment of many medical conditions, including autoimmune and cardiovascular diseases and psychiatric conditions. Identification of molecular differences between typical males and females can provide a valuable basis for exploring conditions differentially affected by sex. Methodology/Principal Findings: Using multiplexed immunoassays, we analyzed 174 serum molecules in 9 independent cohorts of typical individuals, comprising 196 males and 196 females. Sex differences in analyte levels were quantified using a meta-analysis approach and put into biological context using k-means to generate clusters of analytes with distinct biological functions. Natural sex differences were established in these analyte groups and these were applied to illustrate sexually dimorphic Conclusions/Significance: Sex-specific molecular differences were detected in serum of typical controls and these were reproducible across independent cohorts. This study extends current knowledge of sex differences in biological functions involved in metabolism and immune function. Deviations from typical sex differences were found in a cluster of molecules in Asperger syndrome. These findings illustrate the importance of investigating the influence of sex on medical conditions.