Toward Evidence-Based Genetic Research on Lifelong Premature Ejaculation: A Critical Evaluation of Methodology

Recently, four premature ejaculation (PE) subtypes have been distinguished on the basis of the duration of the intravaginal ejaculation latency time (IELT). These four PE subtypes have different etiologies and pathogeneses. Genetic research on PE should consider the existence of these PE subtypes and the accurate measurement of the IELT with a stopwatch. Currently, three methods of genetic research on PE have been used. They differ in the investigated population, tool of measurement, study design, and variables of PE. From animal and human research, it is derived that the central serotonergic system "modulates" ejaculation, whereas the ejaculation (reflex) itself is probably not under direct influence of the serotonergic system, but rather under the influence of other neurotransmitter systems in the spinal cord. For genetic research on PE, it is important to take into account that the (serotonergic) modulation of the IELT is variable among men and may even be absent. This means that serotonergic genetic polymorphisms may only be found in men with PE who respond with an ejaculation delay treatment with a selective serotonin reuptake inhibitor

Capturing naturally occurring emotional suppression as it unfolds in couple interactions

Most research examining the consequences of suppressing emotional expression has focused on either experimentally manipulated and conscious suppression, or self-reported suppression behavior. This study examined suppression as it naturally occurred in couple (n= 105) discussions regarding a challenging topic. A Suppression Index (SI) was created by calculating the difference between continuous self-reports of emotional experience, obtained using cued video recall, and coders’ continuous ratings of expressed emotion. Suppression was common for both men and women, though there was also substantial individual variation. Autocorrelations of the SIwere used to tap Suppressive Rigidity (Srig), or the tendency to inflexibly use suppression throughout the discussions. Srigscores were consistent within individuals across repeated conversations and varied across individuals, suggesting that Srigcaptures stable individual differences. Women’s greater suppression of negative emotions combined with more rigid use of suppression was associated with their own lower relationship satisfaction but not their partners’. These findings indicate that suppressive behavior may be linked to relationship quality, and that it is not just the use of suppression that may matter but how rigidly one applies this regulatory approach

Sexual Dysfunction, Depression and Antidepressants: A Translational Approach

Major depression is frequently associated with sexual dysfunctions. Most antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), induce additional sexual side effects and, although effective antidepressants, deteriorate sexual symptoms, which are the main reason that patients stop antidepressant treatment. Many strategies have been used to circumvent the additional sexual side effects, but results are rather disappointing. Recently, new antidepressants have been introduced, vilazodone and vortioxetine, which seem to lack sexual side effects in the early registration trials. Much research with large numbers of depressed patients and adequate methodological tools still has to confirm in daily use the absence of sexual side effects of new antidepressants. Animal models that in an early phase of drug development may predict putative sexual side effects of new antidepressants are extremely useful and could speed up development of new antidepressants. A rat model of sexual behavior is described that has a very high predictive validity for sexual side effects in man. Several characteristics of present antidepressants with regard to sexual dysfunctions are also present in the rat model and establish its validity. The animal model can also be used in the search for new psychotropics without sexual side effects or for drugs with sexual stimulating activity

Global unions: chasing the dream or building the reality?

This article takes as its theme the global restructuring of capital and its impact on worker organization. It argues for a reassertion of class in any analysis of global solidarity, and assesses the opportunities and barriers to effective global unionization. Rooted in the UK experience, the article analyzes the impact of the European social dimension on trade unions, before taking the discussion into a global dimension. It concludes by suggesting that there are reasons for cautious optimism in terms of solidarity building, despite difficult historical legacies and the common replacement of action with rhetoric

Self-distancing and Avoidance Mediate the Links Between Trait Mindfulness and Responses to Emotional Challenges

Objectives Mindfulness has been linked to better emotion regulation and more adaptive responses to stress across a number of studies, but the mechanisms underlying these links remain to be fully understood. The present study examines links between trait mindfulness (Five Facets of Mindfulness Questionnaire; FFMQ) and participants\u27 responses to common emotional challenges, focusing specifically on the roles of reduced avoidance and more self-distanced engagement as key potential mechanisms driving the adaptive benefits of trait mindfulness. Methods Adults (n = 305, age range: 40-72) from the Second Generation Study of the Harvard Study of Adult Development completed two laboratory-based challenges-public speaking combined with difficult math tasks (the Trier Social Stress Test) and writing about a memory of a difficult moment. State anxiety and sadness were assessed immediately before and after the two stressors. To capture different ways of engaging, measures of self-distancing, avoidance, and persistent worry were collected during the lab session. Results As predicted, individuals who scored higher on the FFMQ experienced less anxiety and persistent worry in response to the social stressors. The FFMQ was also linked to less anxiety and sadness when writing about a difficult moment. The links between mindfulness and negative emotions after the writing task were independently mediated by self-distanced engagement and lower avoidance. Conclusions Affective benefits of trait mindfulness under stress are associated with both the degree and the nature of emotional engagement. Specifically, reduced avoidance and self-distanced engagement may facilitate reflection on negative experiences that is less affectively aversive

Coherence Between Feelings and Heart Rate: Links to Early Adversity and Responses to Stress

Past research suggests that higher coherence between feelings and physiology under stress may confer regulatory advantages. Research and theory also suggest that higher resting vagal tone (rVT) may promote more adaptive responses to stress. The present study examines the roles of response system coherence (RSC; defined as the within-individual covariation between feelings and heart rate over time) and rVT in mediating the links between childhood adversity and later-life responses to acute stressors. Using data from 279 adults from the Second Generation Study of the Harvard Study of Adult Development who completed stressful public speaking and mental arithmetic tasks, we find that individuals who report more childhood adversity have lower RSC, but not lower rVT. We further find that lower RSC mediates the association between adversity and slower cardiovascular recovery. Higher rVT in the present study is linked to less intense cardiovascular reactivity to stress, but not to quicker recovery or to the subjective experience of negative affect after the stressful tasks. Additional analyses indicate links between RSC and mindfulness and replicate previous findings connecting RSC to emotion regulation and well-being outcomes. Taken together, these findings are consistent with the idea that uncoupling between physiological and emotional streams of affective experiences may be one of the mechanisms connecting early adversity to later-life affective responses. These findings also provide evidence that RSC and rVT are associated with distinct aspects of self-regulation under stress. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42761-020-00027-5

Pharmacological studies on the role of 5-HT_1A receptors in male sexual behavior of wildtype and serotonin transporter knockout rats

Brain serotonin (5-HT) neurotransmission plays an important role in male sexual behavior and it is well established that activating 5-HT1A receptors in rats facilitate ejaculatory behavior. However, the relative contribution of 5-HT1A somatodendritic autoreceptors and heteroreceptors in this pro-sexual behavior is unclear. Moreover, it is unclear whether the contribution of somatodendritic 5-HT1A autoreceptors and postsynaptic 5-HT1A heteroreceptors alter when extracellular 5-HT levels are chronically increased. Serotonin transporter knockout (SERT-/-) rats exhibit enhanced extracellular 5-HT levels and desensitized 5-HT1A receptors. These rats model neurochemical changes underlying chronic SSRI-induced sexual dysfunction. We want to determine the role of presynaptic versus postsynaptic 5-HT1A receptors in the pro-sexual effects of 5-HT1A receptor agonists in SERT+/+ and in SERT-/- rats. Therefore, acute effects of the biased 5-HT1A receptor agonists F-13714, a preferential 5-HT1A autoreceptor agonist, or F-15599, a preferential 5-HT1A heteroreceptor agonist, and S15535 a mixed 5-HT1A autoreceptor agonist/heteroreceptor antagonist, on male sexual behavior were assessed. A clear and stable genotype effect was found after training where SERT+/+ performed sexual behavior at a higher level than SERT-/- rats. Both F-15599 and F-13714 induced pro-sexual activity in SERT+/+ and SERT-/- animals. Compared to SERT+/+, the F13714-dose-response curve in SERT-/- rats was shifted to the right. SERT+/+ and SERT-/- rats responded similar to F15599. Within both SERT+/+ and SERT-/- rats the potency of F-13714 was much stronger compared to F-15599. S15535 had no effect on sexual behavior in either genotype. In SERT+/+ and SERT-/- rats that were selected on comparable low sexual activity (SERT+/+ 3 or less ejaculations and SERT-/- 5 or less ejaculations in 10 weeks) S15535 also did not influence sexual behavior. The two biased compounds with differential effects on 5-HT1A auto- and hetero-receptors, exerted pro-sexual activity in both SERT+/+ and SERT-/- rats. Applying these specific pharmacological tools has not solved whether pre- or post-synaptic 5-HT1A receptors are involved in pro-sexual activity. Moreover, the inactivity of S15535 in male sexual behavior in either genotype was unexpected. The question is whether the in vivo pharmacological profile of the different 5-HT1A receptor ligands used, is sufficient to differentiate pre- and/or post-synaptic 5-HT1A receptor contributions in male rat sexual behavior

Tramadol's inhibitory effects on sexual behavior:Pharmacological studies in serotonin transporter knockout rats

(Tramadol is an effective pharmacological intervention in human premature ejaculation (PE). To investigate whether the inhibitory action of tramadol is primarily caused by its selective serotonin reuptake inhibitory (SSRI) effects we tested the dose- response effects of tramadol on sexual behavior in serotonin transporter wild type (SERT (+/+)), heterozygous (SERT (+/-)), and knockout (SERT (-/-)) rats. To investigate whether other mechanisms contribute to the inhibitory effects, WAY100,635, a 5-HT1A receptor antagonist and naloxone, a mu-opioid receptor antagonist, were tested on sexual behavior together with tramadol. Tramadol dose-dependently decreases sexual activity in all genotypes. In all studies, SERT+/- rats did not respond differently from SERT+/+ rats. WAY100,635 did not affect sexual activity in SERT+/+, but dose-dependently reduced sexual activity in SERT-/-. WAY100,635 (0.3 mg/ kg) combined with tramadol (20 mg/ kg) significantly reduced sexual activity in SERT+/+ and even stronger in SERT-/-. Naloxone did not affect sexual behavior consistently in SERT+/+ rats, while in SERT-/- all doses reduced ejaculation frequency mildly. Combining naloxone (20 mg/ kg) and tramadol (20 mg/ kg) decreased ejaculation frequencies in both genotypes. Interestingly, combining tramadol (20 mg/ kg), WAY100,635 (0.3 mg/ kg) and naloxone (20 mg/ kg) led to complete elimination of all sexual activity in both SERT+/+ and SERT-/-. These findings suggest that the inhibitory effects of tramadol on male sexual behavior in SERT+/+ rats is mainly, if not exclusively, due to SERT inhibition, with an important role for 5-HT1A receptors, although influence of other systems (e.g., noradrenergic) cannot be excluded. As SSRIs exert their sexual inhibition after chronic administration, tramadol may be therapeutically attractive as "on demand" therapy for PE

Reconceptualizing Context: A Multilevel Model of the Context of Reception and Second-Generation Educational Attainment

This paper seeks to return scholarly attention to a core intellectual divide between segmented and conventional (or neo-)assimilation approaches, doing so through a theoretical and empirical reconsideration of contextual effects on second-generation outcomes. We evaluate multiple approaches to measuring receiving country contextual effects and measuring their impact on the educational attainment of the children of immigrants. We demonstrate that our proposed measures better predict second-generation educational attainment than prevailing approaches, enabling a multilevel modeling strategy that accounts for the structure of immigrant families nested within different receiving contexts

De WVSD en NVVS richtlijn voor de diagnose en behandeling van vroegtijdige zaadlozing.

Richtlijn voor klinische diagnostiek en behandeling van vroegtijdige zaadlozingDeze Richtlijn is tot stand gekomen door een interdisciplinair internationaal en Nederlands panel van erkende specialisten op het gebied van vroegtijdige zaadlozing met als doel begrijpelijke, praktische en evidence-based aanbevelingen te geven voor de diagnostiek en behandeling van vroegtijdige zaadlozing door huisartsen, seksuologen en specialisten (met name urologen). Erkennende dat niet al het wetenschappelijk bewijs van gelijk niveau is, heeft het ISSM Commitee de wetenschappelijke literatuur doorgenomen en bediscussieerd waardoor bij de aanbevelingen een graad van wetenschappelijkheid gegeven kon worden volgens de Oxford Centre of Evidence-Based Medicine gradaties. Tabel 4 bevat alle relevante aanbevelingen van het Vroegtijdige Zaadlozing ISSM Guidelines Committee. Deze richtlijn bevestigt de ISSM definitie van primaire vroegtijdige zaadlozing en laat zien dat de prevalentie van vroegtijdige zaadlozing aanzienlijk lager is dan eerder is aangenomen. Evidence-based gegevens ten aanzien van biologische en psychologische etiologie van vroegtijdige zaadlozing worden beschreven, evenals op populatie-onderzoek gebaseerde statistiek ten aanzien van normale ejaculatielatentietijden. Korte diagnostische procedures worden aangegeven evenals gevalideerde diagnostische en behandelingsvragenlijsten. Ten slotte, de beste aanbevelingen voor behandeling worden beschreven om een houvast te geven aan de clinicus, die wel of niet bekend is met vroegtijdige zaadlozing, en om de behandeling van zijn patiënt te vergemakkelijken.Wetenschappelijke Vereniging voor Seksuele Disfuncties (WVSD); Nederlandse Vereniging voor Seksuologie (NVVS