The "Chemsex" Phenomenon and Its Relationship with Psychological Variables in Men Who Have Sex with Men.

Chemsex is described as the use of psychoactive substances during sexual activity to sustain, enhance, disinhibit, or facilitate the sexual experience. It preferentially concerns men who have sex with men. The main objective of this study was to examine the relationship between participation in chemsex and the psychological variables impulsivity, sexual assertiveness, and hypersexuality. The sample was composed of 137 Spanish men. A total of 104 participants reported that they had engaged in chemsex, with ages ranging from 19 to 42 years (M = 31.41, SD = 4.83). A total of 33 participants reported that they had never participated in chemsex sessions. The participants were contacted and recruited at social centers, LGBT associations, and key informants. Results showed that men who participated in chemsex reported higher impulsivity, higher hypersexuality, and lower sexual assertiveness than those who have never participated in it. The frequency of participation in chemsex, as well as the number of substances consumed, was positively and significantly correlated with dimensions of impulsivity and hypersexuality. This frequency and this consumption were negatively and significantly correlated with sexual assertiveness. Findings showed significant differences in the psychological variables based on the number of consumed substances (polydrug use/consumption of one substance) and the time of consumption (before, during or before and during sex). In conclusion, the study demonstrates the existence of a clear relationship between the experience of chemsex and psychological factors such as being an impulsive person, presenting hypersexual behavior, and/or having low sexual assertiveness.

Validation of the Spanish Version of the Massachusetts General Hospital-Sexual Functioning Questionnaire (MGH-SFQ) with Sexual Arousal Measures in Men.

Objective: Provide new validity evidence of the Spanish version of the Massachusetts General Hospital-Sexual Functioning Questionnaire (MGH-SFQ) by associating its scores with measures of sexual arousal. Method: In a sample of 48 men, using a quasi-experimental design, sexual functioning, propensity for sexual inhibition/excitation, subjective sexual arousal, and genital response (penile plethysmography recorded with Biopac MP150 equipment) were evaluated. Results: Arousal and erection scores correlated with sexual inhibition due to the threat of performance failure (r = .29; p < .05) and genital response (r = .31; p < .05), respectively. Participants with difficulties in sexual functioning indicated greater sexual inhibition due to the threat of performance failure (p = .04) and lower intensity in their genital response (p = .05). Conclusions: The validity of the measures obtained with the Spanish version of the MGH-SFQ is supported, showing the erection item to be useful for the detection of possible erectile disorders.

Objetivo: Aportar nuevas evidencias de validez a la versión española del Massachusetts General Hospital-Sexual Functioning Questionnaire (MGH-SFQ), asociando sus puntuaciones a medidas de la excitación sexual. Método: En una muestra de 48 hombres, mediante un diseño cuasiexperimental, se evaluó el funcionamiento sexual, la propensión para la excitación/inhibición sexual, la excitación sexual subjetiva y la respuesta genital (pletismografía peniana registrada con un equipo Biopac MP150). Resultados: Las puntuaciones en excitación y erección del MGH-SFQ correlacionaron significativamente con la inhibición sexual por miedo al fallo en el rendimiento sexual (r = .29; p < .05) y con la respuesta genital (r = .31; p < .05), respectivamente. Los participantes con dificultades en el funcionamiento sexual, en comparación con los que mostraron un adecuado funcionamiento, indicaron mayor inhibición sexual por miedo al fallo en el rendimiento sexual (p = .04) y menor intensidad en su respuesta genital (p = .05). Conclusiones: Se avala la validez de las medidas obtenidas con la versión española del MGH-SFQ, mostrándose el ítem de erección útil para la detección de posibles trastornos eréctiles.

Study of Sexual Concordance in Men and Women with Different Typologies of Adherence to the Sexual Double Standard.

Background/Objective: Sexual concordance (i.e., relationship between genital response and subjective sexual arousal) is higher in men than in women. Among the factors that could explain this difference would be the sexual double standard (SDS). Sexual concordance is examined by SDS typologies of adherence (egalitarian, man-favorable, and woman-favorable). Method: During exposure to a film with sexual content, genital response (penile circumference/vaginal pulse amplitude) and self-reported sexual arousal were recorded in 104 young adults (42 men and 62 women), distributed into SDS typologies of adherence on the basis of their scores on the Sexual Double Standard Scale. Results: Sexual concordance was obtained in men and women with egalitarian and man-favorable typology. Subjective sexual arousal explained a significant percentage of the variance in genital response in the egalitarian typology (men: R2  = .32, p < .01; women: R2  = .19, p < .05) and man-favorable typology (men: R2  = .21, p < .05; women: R2  = .23, p < .05). Conclusions: Agreement between genital responsiveness and subjective sexual arousal depends on DES adherence typology.

Antecedentes/Objetivo: La concordancia sexual (i.e., relación entre respuesta genital y excitación sexual subjetiva) parece ser mayor en hombres que en mujeres. Entre los factores que podrían explicar dicha diferencia estaría el doble estándar sexual (DES). Se examina la concordancia sexual en función de la tipología de adhesión al DES (igualitaria, favorable al hombre y favorable a la mujer). Método: Durante la exposición a un filme de contenido sexual, se registró la respuesta genital (circunferencia peniana/amplitud del pulso vaginal) y la excitación sexual autoinformada de 104 adultos jóvenes (42 hombres y 62 mujeres), distribuidos en las tipologías de adhesión al DES a partir de sus puntuaciones en la Sexual Double Standard Scale. Resultados: Se obtuvo concordancia sexual en hombres y mujeres con tipología igualitaria y favorable al hombre. La excitación sexual subjetiva explicó un porcentaje significativo de la varianza de la respuesta genital en la tipología igualitaria (hombres: R2  = 0,32, p < 0,01; mujeres: R2  = 0,19, p < 0,05) y en la favorable al hombre (hombres: R2  = 0,21, p < 0,05; mujeres: R2  = 0,23, p < 0,05). Conclusiones: El acuerdo entre la respuesta genital y la excitación sexual subjetiva depende de la tipología de adhesión al DES.

The Impact of Intimate Partner Violence on Sexual Attitudes, Sexual Assertiveness, and Sexual Functioning in Men and Women.

BACKGROUND: Intimate Partner Violence (IPV) causes physical, sexual, or psychological harm. The association between psychosexual (sexual assertiveness, erotophilia, and attitude towards sexual fantasies) and sexual function (sexual desire, sexual excitation, erection, orgasm capacity, and sexual satisfaction), and the experience of physical and non-physical IPV was assessed. METHODS: Data from 3394 (1766 women, 1628 men) heterosexual adults completed the Spanish version of the Index of Spouse Abuse, scales measuring psychosexual and sexual function, and demographic characteristics were collected. RESULTS: For men, poorer sexual health was associated with an experience of physical abuse (F = 4.41, p < 0.001) and non-physical abuse (F = 4.35, p < 0.001). For women, poorer sexual health was associated with physical abuse (F = 13.38, p < 0.001) and non-physical abuse (F = 7.83, p < 0.001). CONCLUSION: The experience of physical or non-physical abuse has a negative association with psychosexual and sexual functioning in both men and women.

Association between Psychopathological Dimensions and Sexual Functioning/Sexual Arousal in Young Adults.

Psychological-psychiatric factors have a different effect on sexual functioning in men and women. This research aimed to examine the association between psychopathological dimensions and dimensions of sexual functioning in Spanish young adults in two studies. Study 1 examined sexual functioning and psychopathological dimensions in 700 women and 516 men. Study 2 conducted an experimental laboratory task to evaluate subjective sexual arousal and genital sensations when watching visual sexual stimuli in a subsample of participants from Study 1 (143 women and 123 men). As a result, the first study showed that depression and anxiety-related symptoms had a negative effect, both in men and women, and having a partner had a positive influence on the dimensions of sexual functioning. The second study showed that anxiety symptoms were positively associated with subjective sexual arousal in both men and women, and anxiety was associated with the assessment of genital sensations in men. The differences between the results of anxiety may be explained because sexual arousal was evaluated in general terms in Study 1, whereas it was evaluated as a state in Study 2. These findings confirm that the presence of psychopathological symptoms contributes to sexual functioning, as well as the necessity of strengthening mental illness prevention programs that include sexual health components.

Validity evidence and norms of the Spanish versión of the Hurlbert Index of Sexual Fantasy.

BACKGROUND: Sexual fantasies are described as thoughts or mental images with sexual content. The Hurlbert Index of Sexual Fantasy (HISF) evaluates the positive attitude towards sexual fantasies. The objective of this study was to provide validity evidence of the Spanish version of the HISF and to present its standard scores. METHOD: The sample was composed of 3,458 adults from the general Spanish population (1,641 men; 1,817 women), distributed across age groups (18-34, 35-49, and over 50 years old). RESULTS: The unifactorial structure of the Spanish version of the HISF showed strict measurement invariance across sex, age range, and education level. Positive attitudes towards sexual fantasies significantly correlated with erotophilia, sexual assertiveness, sexual desire, and sexual functioning. Also, the scale was useful for differentiating between individuals with sexual functioning difficulties and individuals with no difficulties. Finally, the standard scores were obtained based on sex and age range. CONCLUSIONS: The Spanish version of the HISF is a reliable, valid, and invariant scale for assessing a positive attitude towards sexual fantasies in people with different sociodemographic characteristics.

The Spanish Version of the Sexual Opinion Survey (SOS-6): Evidence of Validity of a Short Version.

The aim of this work was to provide validity evidences of the short Spanish version of the Sexual Opinion Survey (SOS-6). First, a psychometric study was performed to examine the factorial invariance of the scale across different groups. A sample of 1,500 heterosexual adults (50% men, 50% women) from the general Spanish population, aged 18 to 80, was examined. Results showed that the unidimensional model of the SOS-6 is invariant across sex, age range, relationship status, and educational level. Secondly, a laboratory study was performed to determine the relationship between erotophilia and objective and subjective sexual arousal in response to sexual stimuli. The sample consisted of 130 young Spanish university students (46.92% men, 53.08% women) with heterosexual orientation. In men, erotophilia was related to subjective sexual arousal; in women, erotophilia was related to subjective sexual arousal and estimation of genital sensations. In conclusion, this work provides validity evidences of the short version of the SOS-6 and describes the factorial equivalence of the scale across groups and its concurrent validity.

El objetivo de este trabajo fue aportar evidencias de validez a la versión española breve del Sexual Opinion Survey (SOS-6) mediante dos estudios independientes. En primer lugar, se realizó un estudio psicométrico para examinar la invarianza factorial de la escala por diferentes grupos. Se empleó una muestra de 1.500 adultos heterosexuales (50% hombres, 50% mujeres) de la población española general de entre 18 y 80 años de edad. Los resultados mostraron que el modelo unifactorial del SOS-6 es invariante por sexo, rango de edad, estatus de relación de pareja y nivel de estudios. En segundo lugar, se realizó un estudio de laboratorio para determinar la relación de la erotofilia en la excitación sexual objetiva y subjetiva ante estímulos sexuales. La muestra estuvo compuesta por 130 jóvenes universitarios (46,92% hombres, 53,08% mujeres) de nacionalidad española y con orientación heterosexual. En los hombres, la erotofilia se relacionó con la excitación sexual subjetiva; en las mujeres, la erotofilia se asoció tanto con la estimación de la excitación sexual como con la valoración de sensaciones genitales. Como conclusión, este trabajo aporta evidencias de validez a la versión española breve del SOS-6, mostrando su equivalencia por grupos y su validez concurrente.

Relationship between orgasm experience and sexual excitation: validation of the model of the subjective orgasm experience.

The aim of this study was to provide validity evidence of the Model of the Subjective Orgasm Experience (MSOE) associating its components with different types of sexual excitation. A total of 96 participants (48 men and 48 women) performed an experimental laboratory task, in which neutral and erotic content films were presented while the genital response was registered. After exposure to sexual stimulus presentation, participants reported their subjective sexual arousal. In addition, four dimensions (affective, sensory, intimacy, and rewards) of the subjective orgasm experience and the individual propensity for sexual excitation were assessed. Results showed that, in men, the affective, sensory, and rewards dimensions of the orgasm experience significantly correlated with the propensity for becoming sexually excited, and the intimacy dimension correlated with the genital response. In women, the sensory dimension of the orgasm experience positively correlated with the subjective sexual arousal. Types of sexual excitation which previously correlated with the orgasm experience were able to predict its four dimensions. The validation of the MSOE provides a more delimited explanation of the psychological experience of orgasm applicable to both sexes. It is an adequate model for both clinical and research purposes.

Regulation of CD4(+)NKG2D(+) Th1 cells in patients with metastatic melanoma treated with sorafenib: role of IL-15Rα and NKG2D triggering.

Beyond cancer-cell intrinsic factors, the immune status of the host has a prognostic impact on patients with cancer and influences the effects of conventional chemotherapies. Metastatic melanoma is intrinsically immunogenic, thereby facilitating the search for immune biomarkers of clinical responses to cytotoxic agents. Here, we show that a multi-tyrosine kinase inhibitor, sorafenib, upregulates interleukin (IL)-15Rα in vitro and in vivo in patients with melanoma, and in conjunction with natural killer (NK) group 2D (NKG2D) ligands, contributes to the Th1 polarization and accumulation of peripheral CD4(+)NKG2D(+) T cells. Hence, the increase of blood CD4(+)NKG2D(+) T cells after two cycles of sorafenib (combined with temozolomide) was associated with prolonged survival in a prospective phase I/II trial enrolling 63 patients with metastatic melanoma who did not receive vemurafenib nor immune checkpoint-blocking antibodies. In contrast, in metastatic melanoma patients treated with classical treatment modalities, this CD4(+)NKG2D(+) subset failed to correlate with prognosis. These findings indicate that sorafenib may be used as an "adjuvant" molecule capable of inducing or restoring IL-15Rα/IL-15 in tumors expressing MHC class I-related chain A/B (MICA/B) and on circulating monocytes of responding patients, hereby contributing to the bioactivity of NKG2D(+) Th1 cells.

Chronic myeloid leukemic cells trigger poly(ADP-ribose) polymerase-dependent inactivation and cell death in lymphocytes.

NK cells and T cells are commonly dysfunctional in CML, and their status may determine the course of disease. We aimed to define the molecular mechanisms of leukemia-induced immunosuppression with focus on the role of ROS and the PARP-1 pathway of cell death. Malignant granulocytes from patients with BCR-ABL-positive CML expressed the oxygen radical-producing enzyme NOX, produced large amounts of ROS, and triggered extensive cell death in NK cells. Inhibition of PARP-1 maintained NK cell viability in cocultures with suppressive leukemic cells. Under conditions of oxidative stress, PARP-1 inhibition upheld the capacity of NK cells to kill myeloid leukemic cells, in addition to restoring the proliferation and cytokine production of NK cells and cytotoxic T cells. Our findings are suggestive of a novel pathway of relevance to immunosuppression in CML.

Histamine dihydrochloride and low-dose interleukin-2 as post-consolidation immunotherapy in acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Although most patients achieve complete remission (CR) after chemotherapy, the majority suffer from subsequent leukemic relapse, which is associated with poor long-term survival. Thus, new therapies to maintain CR are highly warranted. After the completion of chemotherapy, AML patients have a minimal burden of leukemic cells, which are reportedly susceptible to cytotoxic lymphocytes such as NK cells and T cells. A therapy that boosts the function of these effector cells therefore has the potential to eradicate the malignant clone in AML and prevent relapse, Here, we briefly review the literature on the role of the immune system in AML and introduce the rationale for the use of histamine dihydrochloride (HDC) in conjuction with low-dose IL-2 as relapse-preventive immunotherapy for this disease.

The CD16-/CD56bright subset of NK cells is resistant to oxidant-induced cell death.

Phagocyte-derived reactive oxygen species ("oxygen radicals") have been ascribed a suppressive role in immunoregulation by inducing dysfunction and apoptotic cell death in lymphocytes. Earlier studies show that human NK cells are exceptionally sensitive to oxygen radical-induced apoptosis and functional inhibition. Two subsets of human CD56(+) NK cells have been identified: the highly cytotoxic CD56(dim) cells which constitute >90% of NK cells in peripheral blood, and the less cytotoxic but efficiently cytokine-producing CD56(bright) cells. In this study, we demonstrate that the CD56(bright) subset of NK cells, in contrast to CD56(dim) cells, remains viable and functionally intact after exposure to phagocyte-derived or exogenously added oxygen radicals. The resistance of CD56(bright) cells to oxidative stress was accompanied by a high capacity of neutralizing exogenous hydrogen peroxide, and by a high cell-surface expression of antioxidative thiols. Our results imply that CD56(bright) NK cells are endowed with an efficient antioxidative defense system that protects them from oxygen radical-induced inactivation.

Cutting edge: Antioxidative properties of myeloid dendritic cells: protection of T cells and NK cells from oxygen radical-induced inactivation and apoptosis.

Dendritic cells (DCs) communicate with nonadaptive and adaptive lymphocytes on multiple levels. Efficient DC-lymphocyte interactions require that lymphocytes remain viable and functional also under conditions of oxidative stress, such as in microbial infection or in the malignant microenvironment. For this study, we exposed human T and NK cells to oxidants delivered either by autologous phagocytes or in the form of exogenous hydrogen peroxide. In accordance with earlier studies, these lymphocytes became dysfunctional and subsequently apoptotic. The presence of myeloid DCs efficiently rescued T cells (CD4+ and CD8+) and NK cells from oxidant-induced inactivation and apoptosis. The mechanism of the myeloid DC-mediated lymphocyte protection was, at least in part, explained by the capacity of the myeloid DCs to neutralize extracellular oxygen radicals, which, in turn, was reversible upon coincubation with a catalase inhibitor. Our results are suggestive of a novel aspect of DC-lymphocyte interaction that may have implications for lymphocyte function in inflamed tissue.

NKp46 and NKG2D receptor expression in NK cells with CD56dim and CD56bright phenotype: regulation by histamine and reactive oxygen species.

The cytotoxicity of natural killer (NK) cells is dependent on the interaction between target cell ligands and a series of stimulatory receptors on NK cells. Two of these triggering receptors, the NKp46 natural cytotoxicity receptor (NKp46) and the major histocompatibility complex (MHC) class I-interactive NKG2D receptor, are deficiently expressed by NK cells recovered from patients with acute myeloid leukaemia (AML), but little is known regarding the regulation of NKp46 and NKG2D expression. Here we report that mononuclear and polymorphonuclear phagocytes downregulate the cell surface density of NKp46 and NKG2D on NK cells with CD56(dim) phenotype in vitro by a mechanism that is dependent on the availability of phagocyte-derived reactive oxygen species (ROS). Histamine maintained NKp46 and NKG2D expression despite the presence of inhibitory phagocytes by targeting an H2 receptor on phagocytes. By contrast, NKp46 and NKG2D expression by the CD56(bright) subset of NK cells was resistant to inhibition by phagocytes. Our findings are suggestive of a novel mechanism of relevance to the regulation of NKp46/NKG2D receptor expression. Moreover, our findings suggest that the previously reported action of histamine on NK cell-mediated killing of leukaemic cells may be related to the preservation of activatory NK-cell receptors.

Oxygen radicals induce poly(ADP-ribose) polymerase-dependent cell death in cytotoxic lymphocytes.

Cytotoxic T cells and NK cells will acquire features of apoptosis when exposed to oxygen radicals, but the molecular mechanisms underlying this phenomenon are incompletely understood. We have investigated the role of two enzyme systems responsible for execution of cell death, caspases and the poly(ADP-ribose) polymerase (PARP). We report that although human cytotoxic lymphocytes were only marginally protected by caspase inhibitors, PARP inhibitors completely protected lymphocytes from radical-induced apoptosis and restored their cytotoxic function. The radical-induced, PARP-dependent cell death was accompanied by nuclear accumulation of apoptosis-inducing factor and a characteristic pattern of large-fragment DNA degradation. It is concluded that the PARP/apoptosis-inducing factor axis is critically involved in oxygen radical-induced apoptosis in cytotoxic lymphocytes.

IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection.

Plasma from 173 patients with HCV genotype 1 infection was analyzed for IP-10 levels prior to treatment with pegylated interferon-alpha-2a and ribavirin. Significantly lower IP-10 levels were observed in patients achieving a rapid viral response (RVR) (P < .0001), even in those with body mass index (BMI) > or = 25 kg/m2 (P = .004) and with baseline viral load > or = 2 million IU/mL (P = .001). Similarly, significantly lower IP-10 levels were observed in patients obtaining a sustained viral response (SVR) (P = .0002), including those having higher BMI (P < .05), higher viral load (P = .0005), and both higher BMI and viral load (P < .03). In multivariate logistic regression analyses, a low IP-10 value was independently predictive of both RVR and SVR. A baseline cutoff IP-10 value of 600 pg/mL yielded a negative predictive value (NPV) of 79% (19/24) for all genotype 1-infected patients, which was comparable with that observed using a reduction in HCV-RNA by at least 2 logs after 12 weeks of therapy (NPV 86%; 19/22); by combining the two, 30 of 38 patients (NPV 79%) potentially could have been spared unnecessary therapy. In patients having both higher BMI and viral load, cut-off levels of 150 and 600 pg/mL yielded a positive predictive value (PPV) of 71% and NPV of 100%, respectively. In conclusion, pretreatment IP-10 levels predict RVR and SVR in patients infected with HCV genotype 1, even in those with higher BMI and viral load. A substantial proportion of the latter patients may achieve SVR in spite of unfavorable baseline characteristics if their pretreatment IP-10 level is low. Thus, pretreatment IP-10 analysis may prove helpful in decision-making regarding pharmaceutical intervention.

Interferon (IFN)-gamma-inducible protein-10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN-alpha 2a and ribavirin for chronic hepatitis C virus infection.

BACKGROUND: We investigated associations between interferon (IFN)-gamma-inducible protein (IP)-10 and liver histological results, viral kinetic response, and treatment outcome in patients infected with hepatitis C virus (HCV) genotypes 1-4. METHODS: Plasma IP-10 was monitored before, during, and after treatment with pegylated IFN- alpha 2a and ribavirin in 265 HCV-infected patients. RESULTS: In univariate analyses, a low baseline IP-10 level was significantly associated with low baseline viral load, rapid viral response (RVR), a sustained viral response (SVR), body mass index <25 kg/m2, and less-pronounced fibrosis, inflammation, and steatosis (for HCV genotypes other than 3). When the results of the univariate analyses were included in multivariate analyses, a low plasma IP-10 level, low baseline viral load, and genotype 2 or 3 infection were independent predictors of an RVR and SVR. IP-10 levels decreased 6 weeks into treatment and remained low in patients with an SVR. By contrast, plasma levels of IP-10 rebounded in patients who had detectable HCV RNA after the completion of treatment. Using cutoff IP-10 levels of 150 and 600 pg/mL for predicting an SVR in patients infected with HCV genotype 1 yielded a specificity and sensitivity of 81% and 95%, respectively. CONCLUSION: Baseline IP-10 levels are predictive of the response to HCV treatment.

Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial.

The primary objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.5 mg); both compounds were administered by subcutaneous injection twice daily. Study arms were balanced for age, sex, previous treatment, leukemic karyotypes, time from CR to inclusion, and frequency of secondary leukemia. Three years after enrollment of the last patient, treatment with HDC/IL-2 was found to improve LFS over control in the study population (CR1 + CR > 1, n = 320; P < .01, log-rank test). For patients in CR1 (n = 261), treatment significantly improved LFS (P = .01) with 3-year LFS estimates of 40% (HDC/IL-2) compared with 26% (control). Side effects were typically mild to moderate. These results indicate that HDC/IL-2 treatment offers an efficacious and tolerable treatment for patients with AML in remission.