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

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

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

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

Emerging Issues in Occupational Disease: Mental Health in the Aging Working Population and Cognitive Impairment - A Narrative Review

Cognitive impairment has often been reported in scientific literature as a concern derived from chronic exposure to work-related stress. Organizational factors can contribute to the onset of this concern especially in a susceptible population such as elderly workers. The aim of our study was to review the last five years of scientific literature, focusing on experimental and epidemiological studies, possible mechanisms implicated in the onset of cognitive decline due to work-related stress, and the recent organizational strategies to prevent detrimental effects of stress on cognitive processes. A literature search was performed in scientific platforms Medline and Web of Science, by means of specific string search terms, restricting the search to the years of publication 2014–2019. Thirty-three articles were identified and qualitatively evaluated, reporting narratively the main point of interest. At this stage, six articles were excluded because they did not meet the inclusion criteria. Only a few articles considered the population of the elderly workers, often with a short follow-up period. Strategies to manage stress with organizational procedures are scarce. Mechanisms implicated in the development of cognitive impairment due to stress are not fully explained and seem to include a chronical decrease in the inhibitory process of neurological pathways. Further research that focused on strategies to manage stress in elderly workers, with the aim of preventing cognitive impairment processes, is warranted

Emerging Issues in Occupational Disease: Mental Health in the Aging Working Population and Cognitive Impairment - A Narrative Review

Cognitive impairment has often been reported in scientific literature as a concern derived from chronic exposure to work-related stress. Organizational factors can contribute to the onset of this concern especially in a susceptible population such as elderly workers. The aim of our study was to review the last five years of scientific literature, focusing on experimental and epidemiological studies, possible mechanisms implicated in the onset of cognitive decline due to work-related stress, and the recent organizational strategies to prevent detrimental effects of stress on cognitive processes. A literature search was performed in scientific platforms Medline and Web of Science, by means of specific string search terms, restricting the search to the years of publication 2014-2019. Thirty-three articles were identified and qualitatively evaluated, reporting narratively the main point of interest. At this stage, six articles were excluded because they did not meet the inclusion criteria. Only a few articles considered the population of the elderly workers, often with a short follow-up period. Strategies to manage stress with organizational procedures are scarce. Mechanisms implicated in the development of cognitive impairment due to stress are not fully explained and seem to include a chronical decrease in the inhibitory process of neurological pathways. Further research that focused on strategies to manage stress in elderly workers, with the aim of preventing cognitive impairment processes, is warranted

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

Mal de Debarquement Syndrome: A Matter of Loops?

Introduction: Mal de Debarquement Syndrome (MdDS) is a poorly understood neurological disorder affecting mostly perimenopausal women. MdDS has been hypothesized to be a maladaptation of the vestibulo-ocular reflex, a neuroplasticity disorder, and a consequence of neurochemical imbalances and hormonal changes. Our hypothesis considers elements from these theories, but presents a novel approach based on the analysis of functional loops, according to Systems and Control Theory. Hypothesis: MdDS is characterized by a persistent sensation of self-motion, usually occurring after sea travels. We assume the existence of a neuronal mechanism acting as an oscillator, i.e., an adaptive internal model, that may be able to cancel a sinusoidal disturbance of posture experienced aboard, due to wave motion. Thereafter, we identify this mechanism as a multi-loop neural network that spans between vestibular nuclei and the flocculonodular lobe of the cerebellum. We demonstrate that this loop system has a tendency to oscillate, which increases with increasing strength of neuronal connections. Therefore, we hypothesize that synaptic plasticity, specifically long-term potentiation, may play a role in making these oscillations poorly damped. Finally, we assume that the neuromodulator Calcitonin Gene-Related Peptide, which is modulated in perimenopausal women, exacerbates this process thus rendering the transition irreversible and consequently leading to MdDS. Conclusion and Validation: The concept of an oscillator that becomes noxiously permanent can be used as a model for MdDS, given a high correlation between patients with MdDS and sea travels involving undulating passive motion, and an alleviation of symptoms when patients are re-exposed to similar passive motion. The mechanism could be further investigated utilizing posturography tests to evaluate if subjective perception of motion matches with objective postural instability. Neurochemical imbalances that would render individuals more susceptible to developing MdDS could be investigated through hormonal profile screening. Alterations in the connections between vestibular nuclei and cerebellum, notably GABAergic fibers, could be explored by neuroimaging techniques as well as transcranial magnetic stimulation. If our hypothesis were tested and verified, optimal targets for MdDS treatment could be found within both the neural networks and biochemical factors that are deemed to play a fundamental role in loop functioning and synaptic plasticity