Metabolomic Biomarkers of Prostate Cancer: Prediction, Diagnosis, Progression, Prognosis, and Recurrence

Metabolite profiling is being increasing employed in the study of prostate cancer as a means of identifying predictive, diagnostic, and prognostic biomarkers. This review provides a summary and critique of the current literature. Thirty-three human case-control studies of prostate cancer exploring disease prediction, diagnosis, progression, or treatment response were identified. All but one demonstrated the ability of metabolite profiling to distinguish cancer from benign, tumor aggressiveness, cases who recurred, and those who responded well to therapy. In the subset of studies where biomarker discriminatory ability was quantified, high AUCs were reported that would potentially outperform the current gold standards in diagnosis, prognosis, and disease recurrence, including PSA testing. There were substantial similarities between the metabolites and the associated pathways reported as significant by independent studies, and important roles for abnormal cell growth, intensive cell proliferation, and dysregulation of lipid metabolism were highlighted. The weight of the evidence therefore suggests metabolic alterations specific to prostate carcinogenesis and progression that may represent potential metabolic biomarkers. However, replication and validation of the most promising biomarkers is currently lacking and a number of outstanding methodologic issues remain to be addressed to maximize the utility of metabolomics in the study of prostate cancer.National Institutes of Health (U.S.) (Grant P01 CA055075)National Institutes of Health (U.S.) (Grant CA133891)National Institutes of Health (U.S.) (Grant CA141298)National Institutes of Health (U.S.) (Grant CA136578)National Institutes of Health (U.S.) (Grant UM1 CA167552

NEW SECONDARY METABOLITES IN THE AMPHINOMID FIREWORM HERMODICE CARUNCULATA

Eight betaine-derived novel compounds were found in extracts of the Mediterranean stinging fireworm Hermodice carunculata. The identification of their structures relies on 1D and 2D NMR (Fig. 1-3) and HPLC-ESI/HRMS spectra. Two types of terminal ammonium portions A and B and a series of different alkyl chains were identified (Fig. 4a,b). Their matching provides the structures of uncharacterized secondary metabolites, named carunculines, and their related isomers. These molecules differ from already known trimethylammonium inflammatory compounds (i.e. complanines) isolated from another amphinomid species, for the structures of the terminal ammonium groups (Fig. 4c) [1]. Carunculine anatomical distribution within H. carunculata was assessed by screening through HPLC-ESI/HRMS (Fig. 5, Table 1): their occurrence was revealed in all the body parts analyzed, both involved in predator-prey interactions [2], and mainly in the digestive apparatus. The results achieved reveal an array of different novel compounds from a chemically unknown species, improving knowledge on Marine Animal Products with chemical and biological potential for bioprospection [3]. Overall, these data reinforce the necessity of studying poorly-investigated taxa to expand knowledge on animal venom biology, their mechanisms of action and exploitation as promising source of drug molecule

Endocrine correlates of male breast cancer risk: a case-control study in Athens, Greece

We studied the relation of certain endocrine-related variables among 23 cases of male breast cancer and 76 apparently healthy male controls. There were significant inverse associations with smoking (P = 0.03), birth order (P = 0.02) and reported frequency of orgasms in later life (P = 0.0004). The study provides strong indirect evidence that endocrine factors are important in the aetiology of male breast cancer. © 2000 Cancer Research Campaig

A Pilot Study of Gender Differences in Sexual Arousal of Patients With OCD: The Moderator Roles of Attachment and Contamination Symptoms

Sexual arousal is often impaired in patients with obsessive–compulsive disorder (OCD). However, little is known about the factors related to this impairment: no study focused on the role of gender-based effects of attachment styles and contamination symptoms. The Dual Control Model assumes three processes driving sexual arousal: sexual excitation (SE), sexual inhibition (SI) due to threat of performance failure, and SI due to threat of performance consequences (e.g., getting contaminated with sexually transmitted diseases). In a group of OCD patients, we hypothesized that (a) women report lower SE and higher SI thanmen; (b) patients with insecure (both anxious and avoidant) attachment styles show lower SE and higher SI; (c) attachment styles moderate the relation between gender and sexual arousal (respectively, for women, higher attachment anxiety, and for men higher attachment avoidance were related to impaired sexual arousal (higher SE and SI) controlling for OCD severity); and (d) contamination symptoms moderate the relation between gender and sexual impairment (women with contamination symptoms show impaired sexual arousal). Seventy-two OCD patients (37.50% women) completed the Obsessive–Compulsive Inventory-Revised, Attachment Styles Questionnaire and Sexual Inhibition/Sexual Excitation Scales. In contrast with our hypotheses, women reported higher SE and lower SI due to threat of performance consequences than men. Patients with higher attachment avoidance (discomfort with intimacy) but also confidence in self and others had higher SE. Women with attachment avoidance (i.e., discomfort with intimacy) had lower SE, while women with attachment anxiety (i.e., preoccupations with relationships) had higher SI due to negative performance consequences. Women with contamination symptoms had higher SI due to performance failure but lower SI due to performance consequences. The present preliminary findings suggest that sexual arousal impairment should be evaluated during the assessment of OCD patients, and gender-based effects of attachment styles and contamination symptoms should be considered during personalized treatment planning

Stigma and discrimination (Sad) at the time of the sars-cov-2 pandemic

Infectious disease control is a crucial public health issue. Although it is important to urgently perform public health measures in order to reduce the risk of spread, it could end up stigmatizing entire groups of people rather than offering control measures based on sound scientific principles. This “us” versus “them” dynamic is common in stigmatization, in general, and indicates a way in which disease stigma can be viewed as a proxy for other types of fears, especially xenophobia and general fear of outsiders. The pandemic risk associated with SARS-CoV-2 infection led us to consider, among other related issues, how stigma and discrimination remain serious barriers to care for people suspected of being infected, even more if they are assisting professions, such as health workers, employed in emergency response. The purpose of this review is to evaluate and promote the importance of psychological aspects of the stigma and social discrimination (SAD) in pandemic realities and, more specifically, nowadays, in the context of SARS-CoV-2/COVID-19. Just as it happened with HIV, HCV, tuberculosis, and Zika, stigma and discrimination undermine the social fabric compromising the ethics and principles of civilization to which each individual in entitled. Recognizing disease stigma history can give us insight into how, exactly, stigmatizing attitudes are formed, and how they are disbanded. Instead of simply blaming the ignorance of people espousing stigmatizing attitudes about certain diseases, we should try to understand precisely how these attitudes are formed so that we can intervene in their dissemination. We should also look at history to see what sorts of interventions against stigma may have worked in the past. Ongoing research into stigma should evaluate what has worked in the past, as above-mentioned, providing us with some clues as to what might work in the current pandemic emergency, to reduce devastating discrimination that keeps people from getting the care they need. We propose a systematic and historical review, in order to create a scientific and solid base for the following SAD analysis. The aim is to propose a coping strategy to face stigma and discrimination (SAD) related to SARS-CoV-2/COVID-19 pandemic outbreak, borrowing coping strategy tools and solutions from other common contagious diseases. Furthermore, our study observes how knowledge, education level, and socioeconomic status (SES) can influence perception of SARS-CoV-2/ COVID-19 risk in a digital world, based on previous research, best practices, and evidence-based research

The JDCS model and blue-collar bullying: Decent working conditions for a healthy environment

Violence in the workplace and its health consequences still represent one of the main obstacles to obtaining decent working conditions. In particular, blue-collar workers run a greater risk of experiencing episodes of violence, also because of a lack of autonomy and fewer social interactions. According to the work environment hypothesis, factors such as high workload, lack of social support and lack of job control represent the antecedents of workplace bullying. Following the job demand-control-support model (JDCS), violence can be the symptom of a high-strain environment. Moreover, it is still unclear if workplace bullying can mediate the effects of work-related stress on workers’ health outcomes. The aim of the present study is to analyse the relationship between the components of the JDCS and the health of the workers considering workplace bullying as a mediating variable. By a cross sectional study design, we tested the following theoretical hypotheses: first, JDCS components (conceptualized as stress) are supposed to significantly predict the level of workers’ health. Second, workplace bullying is supposed to mediate the relationship between the JDCS components and the level of health. The sample consists of 400 blue-collars from three different Italian companies. Work-related stress, health outcomes and workplace bullying were measured by specific self-administered questionnaires and the relationships between the variables of interest were tested through a structural equation model (SEM) analysis. The results showed that while the direct relationship between the components of the JDCS and the level of psychological health is weaker (standardized path coefficients SPC = 0.21), the partial mediation hypothesis shows that workplace bullying mediate the relationship between JDCS components and health outcomes (χ2/df ratio = 2.70; path from stress to workplace bullying SPC = 0.78; path from workplace bullying to general health SPC = 0.51; p = 0.01). The JDCS components (workload, lack of control, lack of support) are useful predictors for workplace bullying. On the other hand, bullying plays a mediating role between the stress experienced and the health consequences. The present study adds new insights into the relationship between violence seen as a form of social behavioural strain and the psychological health of workers. The theoretical and practical implications are discussed. Future research on blue-collars could use longitudinal designs in order to analyse the relationship between social environment, job design and strain reactions

Effect of Valproate and Antidepressant Drugs on Clozapine Metabolism in Patients With Psychotic Mood Disorders

BACKGROUND: The aim of the present study was to appraise retrospectively the influence of valproate (VPA) and antidepressants (ADs) on the steady-state plasma concentrations of clozapine (CLZ), the prototype of various second-generation antipsychotics, norclozapine (NCLZ, its main metabolite), and their ratio (NCLZ:CLZ). METHODS: Sixty-seven psychotic patients with a prevalent diagnosis of bipolar disorder were studied. We then analyzed data altogether and subdivided them into 4 groups, according to pharmacological treatments: #1 CLZ (n = 21), #2 CLZ plus ADs (n = 13), #3 CLZ plus VPA (n = 16), and #4 CLZ plus ADs plus VPA (n = 17). RESULTS: First, significant positive between CLZ and NCLZ plasma levels (in nanograms/milliliter) and the drug daily dosages (in milligrams/kilogram of body weight) (n = 67) were observed (Spearman: rCLZ = 0.49; rNCLZ = 0.61; P < 0.001). We then normalized by given doses CLZ and NCLZ plasma levels, natural log transformed them, and performed analysis of variance factor analyses followed by pairwise comparisons, performed on the 4 groups and the 3 CLZ parameters. We identified significant drug effects on (1) CLZ plasma levels, significantly higher in group #2 versus group #1, and (2) NCLZ:CLZ ratio, lower in group #2 versus groups #1 and #3. Significant drug × gender interactions were observed in group #3, showing higher NCLZ levels and NCLZ:CLZ ratios in men compared with women. CONCLUSIONS: Despite its inherent limitations, this observational study confirms the significant increase in plasma CLZ concentrations and reduction in NCLZ:CLZ ratio when this drug was coadministered with ADs (group #2), an effect apparently counteracted by VPA (group #4). The drug × gender interactions in patients taking both CLZ and VPA (group #3) warrant further prospective study

HRV in active-duty special forces and public order military personnel

Heart rate variability (HRV) is a simple, non-invasive, real-time analyzable, and highly reproducible measurement that captures incidences for assessing a person’s health and physical condition. Public security jobs are characterized by major exposure to risk factors known to influence the cardiovascular response to stimuli, e.g., night shifts, highly physically demanding activity, and acute stress activity. This study aimed to evaluate the HRV parameters in a population of 112 male personnel of the special forces and public order of the Carabinieri, aged 25-59, when engaged in several duty tasks, such as paratroopers, night shift police station officers, night shift patrol, dynamic precision shooting evaluative team, dynamic precision shooting non-evaluative team, and office clerks (used as control group). During the specific task of each participant, the HRV parameters were collected with wearable devices and processed. The HRV parameters in the time and frequency domains collected were average heart rate, standard deviation of all normal RR intervals, root mean square of successive differences in adjacent normal-to-normal (NN) intervals, very-low-frequency power, low-frequency power, high-frequency power, stress index, parasympathetic nervous system activity index, and sympathetic nervous system activity index. Parametric tests for independent series to compare the HRV parameters by subgroups within the study subjects were used. A multivariate linear regression analysis was conducted to evaluate the association between the HRV parameters and some personal and organizational factors. The comparison between different subgroups showed that activities with a high demand for concentration and precision, as is the case with paratroopers and dynamic precision shooters, differ significantly from activities that can be defined as routine, such as office work. Other activities, such as patrolling or remote management from operations centers, although including critical elements, did not deviate significantly from the control group. The study of HRV parameters is therefore a useful tool for occupational physicians, both for addressing work suitability assessments and for better targeting health promotion campaigns, to be considered as being aimed at monitoring the subject’s physiological parameters, and not at the diagnosis of any pathological condition, which should always be carried out by the medical specialist