Personalization of prostate cancer prevention and therapy: are clinically qualified biomarkers in the horizon?

Prostate cancer remains the most common malignancy among men and the second leading cause of male cancer-related mortality. Death from this disease is invariably due to resistance to androgen deprivation therapy. Our improved understanding of the biology of prostate cancer has heralded a new era in molecular anticancer drug development, with multiple novel anticancer drugs for castration resistant prostate cancer now entering the clinic. These include the taxane cabazitaxel, the vaccine sipuleucel-T, the CYP17 inhibitor abiraterone, the novel androgen receptor antagonist MDV-3100 and the radionuclide alpharadin. The management and therapeutic landscape of prostate cancer has now been transformed with this growing armamentarium of effective antitumor agents. This review discusses strategies for the prevention and personalization of prostate cancer therapy, with a focus on the development of predictive and intermediate endpoint biomarkers, as well as novel clinical trial designs that will be crucial for the optimal development of such anticancer therapeutics

Defining the Differences Between Episodic Migraine and Chronic Migraine

Chronic migraine (CM) and episodic migraine (EM) are part of the spectrum of migraine disorders, but they are distinct clinical entities. Population-based studies have shown that those with CM demonstrate higher individual and societal burden because they are significantly more disabled than those with EM and have greater impaired quality of life both inside and outside the home. Proper diagnosis of both conditions requires clearly defined clinical criteria. Diagnosis enables the initiation of appropriate treatments and risk-factor modification, which ultimately improve functional status and quality of life for persons with migraine. Recognizing that both disorders are on the spectrum of migraine, this review serves as a guide to define the disease state of CM as distinct from EM in terms of clinical, epidemiological, sociodemographic, and comorbidity profiles

A new, large-bodied omnivorous bat (Noctilionoidea: Mystacinidae) reveals lost morphological and ecological diversity since the Miocene in New Zealand

A new genus and species of fossil bat is described from New Zealand's only pre-Pleistocene Cenozoic terrestrial fauna, the early Miocene St Bathans Fauna of Central Otago, South Island. Bayesian total evidence phylogenetic analysis places this new Southern Hemisphere taxon among the burrowing bats (mystacinids) of New Zealand and Australia, although its lower dentition also resembles Africa's endemic sucker-footed bats (myzopodids). As the first new bat genus to be added to New Zealand's fauna in more than 150 years, it provides new insight into the original diversity of chiropterans in Australasia. It also underscores the significant decline in morphological diversity that has taken place in the highly distinctive, semi-terrestrial bat family Mystacinidae since the Miocene. This bat was relatively large, with an estimated body mass of ~40 g, and its dentition suggests it had an omnivorous diet. Its striking dental autapomorphies, including development of a large hypocone, signal a shift of diet compared with other mystacinids, and may provide evidence of an adaptive radiation in feeding strategy in this group of noctilionoid bats

A survey of energy drink consumption patterns among college students

<p>Abstract</p> <p>Background</p> <p>Energy drink consumption has continued to gain in popularity since the 1997 debut of Red Bull, the current leader in the energy drink market. Although energy drinks are targeted to young adult consumers, there has been little research regarding energy drink consumption patterns among college students in the United States. The purpose of this study was to determine energy drink consumption patterns among college students, prevalence and frequency of energy drink use for six situations, namely for insufficient sleep, to increase energy (in general), while studying, driving long periods of time, drinking with alcohol while partying, and to treat a hangover, and prevalence of adverse side effects and energy drink use dose effects among college energy drink users.</p> <p>Methods</p> <p>Based on the responses from a 32 member college student focus group and a field test, a 19 item survey was used to assess energy drink consumption patterns of 496 randomly surveyed college students attending a state university in the Central Atlantic region of the United States.</p> <p>Results</p> <p>Fifty one percent of participants (<it>n </it>= 253) reported consuming greater than one energy drink each month in an average month for the current semester (defined as energy drink user). The majority of users consumed energy drinks for insufficient sleep (67%), to increase energy (65%), and to drink with alcohol while partying (54%). The majority of users consumed one energy drink to treat most situations although using three or more was a common practice to drink with alcohol while partying (49%). Weekly jolt and crash episodes were experienced by 29% of users, 22% reported ever having headaches, and 19% heart palpitations from consuming energy drinks. There was a significant dose effect only for jolt and crash episodes.</p> <p>Conclusion</p> <p>Using energy drinks is a popular practice among college students for a variety of situations. Although for the majority of situations assessed, users consumed one energy drink with a reported frequency of 1 – 4 days per month, many users consumed three or more when combining with alcohol while partying. Further, side effects from consuming energy drinks are fairly common, and a significant dose effect was found with jolt and crash episodes. Future research should identify if college students recognize the amounts of caffeine that are present in the wide variety of caffeine-containing products that they are consuming, the amounts of caffeine that they are consuming in various situations, and the physical side effects associated with caffeine consumption.</p

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

<p>Abstract</p> <p>Background</p> <p>The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silico<it/>model of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated.</p> <p>Results</p> <p>The in silico<it/>SBML model reflected the in vivo<it/>aging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA), increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation.</p> <p>Conclusion</p> <p>Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitro<it/>and in vivo<it/>studies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people.</p

Migraine and psychiatric comorbidity: a review of clinical findings

Migraine is an extremely common disorder. The underlying mechanisms of this chronic illness interspersed with acute symptoms appear to be increasingly complex. An important aspect of migraine heterogeneity is comorbidity with other neurological diseases, cardiovascular disorders, and psychiatric illnesses. Depressive disorders are among the leading causes of disability worldwide according to WHO estimation. In this review, we have mainly considered the findings from general population studies and studies on clinical samples, in adults and children, focusing on the association between migraine and psychiatric disorders (axis I of the DSM), carried over after the first classification of IHS (1988). Though not easily comparable due to differences in methodology to reach diagnosis, general population studies generally indicate an increased risk of affective and anxiety disorders in patients with migraine, compared to non-migrainous subjects. There would also be a trend towards an association of migraine with bipolar disorder, but not with substance abuse/dependence. With respect to migraine subtypes, comorbidity mainly involves migraine with aura. Patients suffering from migraine, however, show a decreased risk of developing affective and anxiety disorders compared to patients with daily chronic headache. It would also appear that psychiatric disorders prevail in patients with chronic headache and substance use than in patients with simple migraine. The mechanisms underlying migraine psychiatric comorbidity are presently poorly understood, but this topic remains a priority for future research. Psychiatric comorbidity indeed affects migraine evolution, may lead to chronic substance use, and may change treatment strategies, eventually modifying the outcome of this important disorder

Hippurate as a metabolomic marker of gut microbiome diversity: Modulation by diet and relationship to metabolic syndrome

Reduced gut microbiome diversity is associated with multiple disorders including metabolic syndrome (MetS) features, though metabolomic markers have not been investigated. Our objective was to identify blood metabolite markers of gut microbiome diversity, and explore their relationship with dietary intake and MetS. We examined associations between Shannon diversity and 292 metabolites profiled by the untargeted metabolomics provider Metabolon Inc. in 1529 females from TwinsUK using linear regressions adjusting for confounders and multiple testing (Bonferroni: P < 1.71 × 10−4). We replicated the top results in an independent sample of 420 individuals as well as discordant identical twin pairs and explored associations with self-reported intakes of 20 food groups. Longitudinal changes in circulating levels of the top metabolite, were examined for their association with food intake at baseline and with MetS at endpoint. Five metabolites were associated with microbiome diversity and replicated in the independent sample. Higher intakes of fruit and whole grains were associated with higher levels of hippurate cross-sectionally and longitudinally. An increasing hippurate trend was associated with reduced odds of having MetS (OR: 0.795[0.082]; P = 0.026). These data add further weight to the key role of the microbiome as a potential mediator of the impact of dietary intake on metabolic status and health

Impact of a parent-child sexual communication campaign: results from a controlled efficacy trial of parents

<p>Abstract</p> <p>Background</p> <p>Prior research supports the notion that parents have the ability to influence their children's decisions regarding sexual behavior. Yet parent-based approaches to curbing teen pregnancy and STDs have been relatively unexplored. The Parents Speak Up National Campaign (PSUNC) is a multimedia campaign that attempts to fill this void by targeting parents of teens to encourage parent-child communication about waiting to have sex. The campaign follows a theoretical framework that identifies cognitions that are targeted in campaign messages and theorized to influence parent-child communication. While a previous experimental study showed PSUNC messages to be effective in increasing parent-child communication, it did not address how these effects manifest through the PSUNC theoretical framework. The current study examines the PSUNC theoretical framework by 1) estimating the impact of PSUNC on specific cognitions identified in the theoretical framework and 2) examining whether those cognitions are indeed associated with parent-child communication</p> <p>Methods</p> <p>Our study consists of a randomized efficacy trial of PSUNC messages under controlled conditions. A sample of 1,969 parents was randomly assigned to treatment (PSUNC exposure) and control (no exposure) conditions. Parents were surveyed at baseline, 4 weeks, 6 months, 12 months, and 18 months post-baseline. Linear regression procedures were used in our analyses. Outcome variables included self-efficacy to communicate with child, long-term outcome expectations that communication would be successful, and norms on appropriate age for sexual initiation. We first estimated multivariable models to test whether these cognitive variables predict parent-child communication longitudinally. Longitudinal change in each cognitive variable was then estimated as a function of treatment condition, controlling for baseline individual characteristics.</p> <p>Results</p> <p>Norms related to appropriate age for sexual initiation and outcome expectations that communication would be successful were predictive of parent-child communication among both mothers and fathers. Treatment condition mothers exhibited larger changes than control mothers in both of these cognitive variables. Fathers exhibited no exposure effects.</p> <p>Conclusions</p> <p>Results suggest that within a controlled setting, the "wait until older norm" and long-term outcome expectations were appropriate cognitions to target and the PSUNC media materials were successful in impacting them, particularly among mothers. This study highlights the importance of theoretical frameworks for parent-focused campaigns that identify appropriate behavioral precursors that are both predictive of a campaign's distal behavioral outcome and sensitive to campaign messages.</p

CYP17 blockade by abiraterone: further evidence for frequent continued hormone-dependence in castration-resistant prostate cancer

The limited prognosis of patients with castration-resistant prostate cancer (CRPC) on existing hormonal manipulation therapies calls out for the urgent need for new management strategies. The novel, orally available, small-molecule compound, abiraterone acetate, is undergoing evaluation in early clinical trials and emerging data have shown that the selective, irreversible and continuous inhibition of CYP17 is safe with durable responses in CRPC. Importantly, these efficacy data along with strong preclinical evidence indicate that a significant proportion of CRPC remains dependant on ligand-activated androgen receptor (AR) signalling. Coupled with the use of innovative biological molecular techniques, including the characterisation of circulating tumour cells and ETS gene fusion analyses, we have gained insights into the molecular basis of CRPC. We envision that a better understanding of the mechanisms underlying resistance to abiraterone acetate, as well as the development of validated predictive and intermediate endpoint biomarkers to aid both patient selection and monitor response to treatment, will improve the outcome of CRPC patients