Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions

Enhanced ERbeta immunoexpression and apoptosis in the germ cells of cimetidine-treated rats

<p>Abstract</p> <p>Background</p> <p>Cimetidine, refereed as antiandrogenic drug, causes hormonal changes in male patients such as increased testosterone and FSH levels. In the rat testis, structural alterations in the seminiferous tubules have been related to germ cell loss and Sertoli cell death by apoptosis. Regarding the important role of Sertoli cells in the conversion of testosterone into estrogen, via aromatase, the immunoexpression of estrogen receptors-beta (ERbeta) was evaluated in the germ cells of untreated and treated rats with cimetidine. A relationship between ERbeta immunoreactivity and apoptosis was also investigated in the germ cells of damaged tubules.</p> <p>Methods</p> <p>Immunohistochemistry for detection of ERbeta and TUNEL method were performed in testicular sections of adult male rats treated with 50 mg/Kg of cimetidine (CmG) or saline solution (CG) for 52 days.</p> <p>Results</p> <p>In CG, a cytoplasmic immunoexpression for ERbeta was observed in spermatogonia, primary spermatocytes and spermatids. An evident ERbeta immunoreactivity was always observed in the flagellum and residual bodies of late spermatids. In CmG, the cytoplasm or cytoplasm and nuclei of germ cells of the damaged tubules by cimetidine showed enhanced ERbeta immunostaining. TUNEL-labeling was usually observed in the same germ cell types exhibiting enhanced ERbeta immunoreactivity.</p> <p>Conclusion</p> <p>The presence of ERbeta immunolabeling in the flagellum and residual bodies of spermatids reinforces the role of estrogen in spermiogenesis. The overexpression of ERbeta in the germ cells of CmG could be related to a possible interference of cimetidine on tubular androgenization and/or on the intratubular aromatase due to Sertoli cell damage. The parallelism between ERbeta overexpression and apoptosis indicates a participation of ERbeta on germ cell death.</p

High "Normal" blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the PATH through Life Study

Context:Type 2 diabetes is associated with cerebral atrophy, cognitive impairment and dementia. We recently showed higher glucose levels in the normal range not to be free of adverse effects and to be associated with greater hippocampal and amygdalar atrophy in older community-dwelling individuals free of diabetes.Objective:This study aimed to determine whether blood glucose levels in the normal range

Is the process of delivery of an individually tailored lifestyle intervention associated with improvements in LDL cholesterol and multiple lifestyle behaviours in people with Familial Hypercholesterolemia?

<p>Abstract</p> <p>Background</p> <p>More insight in the association between reach, dose and fidelity of intervention components and effects is needed. In the current study, we aimed to evaluate reach, dose and fidelity of an individually tailored lifestyle intervention in people with Familial Hypercholesterolemia (FH) and the association between intervention dose and changes in LDL-Cholesterol (LDL-C), and multiple lifestyle behaviours at 12-months follow-up.</p> <p>Methods</p> <p>Participants (n = 181) randomly allocated to the intervention group received the PRO-FIT intervention consisting of computer-tailored lifestyle advice (<it>PRO-FIT*advice</it>) and counselling (face-to-face and telephone booster calls) using Motivational Interviewing (MI). According to a process evaluation plan, intervention reach, dose delivered and received, and MI fidelity were assessed using the recruitment database, website/counselling logs and the Motivational Interviewing Treatment Integrity (MITI 3.1.1.) code. Regression analyses were conducted to explore differences between participant and non-participant characteristics, and the association between intervention dose and change in LDL-C, and multiple lifestyle behaviours.</p> <p>Results</p> <p>A 34% (n = 181) representative proportion of the intended intervention group was reached during the recruitment phase; participants did not differ from non-participants (n = 623) on age, gender and LDL-C levels. Of the participants, 95% received a <it>PRO-FIT*advice</it> log on account, of which 49% actually logged on and completed at least one advice module. Nearly all participants received a face-to-face counselling session and on average, 4.2 telephone booster calls were delivered. None of the face-to-face sessions were implemented according to MI guidelines. Overall, weak non-significant positive associations were found between intervention dose and LDL-C and lifestyle behaviours.</p> <p>Conclusions</p> <p>Implementation of the PRO-FIT intervention in practice appears feasible, particularly <it>PRO-FIT*advice</it>, since it can be relative easily implemented with a high dose delivered. However, only less than half of the intervention group received the complete intervention-package as intended. Strategies to let participants optimally engage in using web-based computer-tailored interventions like <it>PRO-FIT*advice</it> are needed. Further, more emphasis should be put on more extensive MI training and monitoring/supervision.</p> <p>Trial registration</p> <p>NTR1899 at ww.trialregister.nl.</p

Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution

The cancer immunoediting hypothesis assumes the immune system sculpts the cancer genome. Here the authors show, in a mouse model, that neutral evolution outweighs the effects of immunoselection and that immune checkpoint blockade potentiates the immunoediting, switching the system to non-neutral evolution

Spatio-Temporal Progression of Grey and White Matter Damage Following Contusion Injury in Rat Spinal Cord

Cellular mechanisms of secondary damage progression following spinal cord injury remain unclear. We have studied the extent of tissue damage from 15 min to 10 weeks after injury using morphological and biochemical estimates of lesion volume and surviving grey and white matter. This has been achieved by semi-quantitative immunocytochemical methods for a range of cellular markers, quantitative counts of white matter axonal profiles in semi-thin sections and semi-quantitative Western blot analysis, together with behavioural tests (BBB scores, ledged beam, random rung horizontal ladder and DigiGait™ analysis). We have developed a new computer-controlled electronic impactor based on a linear motor that allows specification of the precise nature, extent and timing of the impact. Initial (15 min) lesion volumes showed very low variance (1.92±0.23 mm3, mean±SD, n = 5). Although substantial tissue clearance continued for weeks after injury, loss of grey matter was rapid and complete by 24 hours, whereas loss of white matter extended up to one week. No change was found between one and 10 weeks after injury for almost all morphological and biochemical estimates of lesion size or behavioural methods. These results suggest that previously reported apparent ongoing injury progression is likely to be due, to a large extent, to clearance of tissue damaged by the primary impact rather than continuing cell death. The low variance of the impactor and the comprehensive assessment methods described in this paper provide an improved basis on which the effects of potential treatment regimes for spinal cord injury can be assessed

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks in proton-proton collisions at root s=13TeV

A search for dark matter produced in association with a Higgs boson decaying to a pair of bottom quarks is performed in proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the LHC. The analyzed data sample corresponds to an integrated luminosity of 35.9 fb(-1). The signal is characterized by a large missing transverse momentum recoiling against a bottom quark-antiquark system that has a large Lorentz boost. The number of events observed in the data is consistent with the standard model background prediction. Results are interpreted in terms of limits both on parameters of the type-2 two-Higgs doublet model extended by an additional light pseudoscalar boson a (2HDM+a) and on parameters of a baryonic Z simplified model. The 2HDM+a model is tested experimentally for the first time. For the baryonic Z model, the presented results constitute the most stringent constraints to date.Peer reviewe