Why Is Impaired Sexual Function Distressing to Men? Consequences of Impaired Male Sexual Function and Their Associations With Sexual Well-Being.

INTRODUCTION: According to theoretical models of sexual dysfunction, the complex association between male sexual function and subjective sexual well-being (ie, sexual satisfaction and distress) may be partially mediated by specific "consequences" of impaired function, but little research has assessed the frequency of specific consequences or their association with well-being. AIM: To pilot a scale assessing consequences of impaired male sexual function, and test whether specific consequences (eg, disruption of sexual activity, negative partner responses) mediated the association between sexual function and well-being. METHODS: 166 men in sexually active heterosexual relationships completed self-report measures. A majority of men self-identified as experiencing impaired sexual function in the past month. MAIN OUTCOME MEASURE: Sexual Satisfaction Scale, International Index of Erectile Function, and Measure of Sexual Consequences. RESULTS: 17 specific consequences were reported with at least moderate frequency and were rated at least somewhat distressing. A factor analysis suggested 3 distinct categories of consequences: barrier to sex and pleasure, negative partner emotional responses, and impaired partner sexual function. These factors and the overall scale exhibited acceptable internal and test-retest reliability and each was significantly associated with multiple facets of sexual function and well-being. Frequency of sexual consequences significantly mediated the association between sexual function and well-being, with the strongest and most consistent indirect effects being found for the barrier to sex and pleasure factor. CLINICAL IMPLICATIONS: Consequences of impaired sexual function on one's sexual experiences may be an important maintaining factor of sexual dysfunction and reduction in these consequences may represent a mechanism of action for psychological treatments. STRENGTH AND LIMITATIONS: Strengths included a relatively large sample with a diverse range of sexual function and well-being, as well as modern statistical analyses to assess factor structure and mediation effects. Limitations included the use of self-report scales with limited independent evidence of validity and reliability for use with male samples, as well as the cross-sectional methods that preclude strong conclusions regarding causal relationships. CONCLUSION: Sexual consequences represent potential maintaining factors of male sexual dysfunction and may represent key targets of cognitive behavioral treatments. Stephenson KR, Truong L, Shimazu L. Why is impaired sexual function distressing to men? Consequences of impaired male sexual function and their associations with sexual well-being. J Sex Med 2018;15:1336-1349.

Rational design of carbamate-based dual binding site and central AChE inhibitors by a "biooxidisable" prodrug approach: Synthesis, in vitro evaluation and docking studies.

Herein, we report a new class of dual binding site AChE inhibitor 4 designed to exert a central cholinergic activation thanks to a redox-activation step of a prodrug precursor 3. Starting from potent pseudo-irreversible quinolinium salts AChE inhibitors 2 previously reported, a new set of diversely substituted quinolinium salts 2a-p was prepared and assayed for their inhibitory activity against AChE. Structure-activity relationship (SAR) analysis of 2a-p coupled with molecular docking studies allowed us to determine which position of the quinolinium scaffold may be considered to anchor the phtalimide fragment presumed to interact with the peripheral anionic site (PAS). In addition, molecular docking provided insight on the linker length required to connect both quinolinium and phatlimide moieties without disrupting the crucial role of quinolinium salt moiety within the catalytic active site (CAS); namely placing the carbamate in the correct position to trigger carbamylation of the active-site serine hydroxyl. Based on this rational design, the putative dual binding site inhibitor 4 and its prodrug 3 were synthesized and subsequently evaluated in vitro against AChE. Pleasingly, whereas compound 4 showed to be a highly potent inhibitor of AChE (IC50 = 6 nM) and binds to AChE-PAS to the same extent as donepezil, its prodrug 3 revealed to be inactive (IC50 > 10 µM). These preliminary results constitute one of the few examples of carbamate-based dual binding site AChE inhibitors.

First total H+/Li+ ion exchange in garnet-type Li5La3Nb2O12 using organic acids and studies on the effect of Li stuffing.

Garnet-type Li(5+x)Ba(x)La(3-x)Nb(2)O(12) (x = 0, 0.5, 1) was prepared using a ceramic method, and H(+)/Li(+) ion exchange was performed at room temperature using organic acids, such as CH(3)COOH and C(6)H(5)COOH, as proton sources. Thermogravimetric analysis showed that H(+)/Li(+) ion exchange was nearly (100%) completed using the x = 0 member with CH(3)COOH, while it proceeded to about 40% for x = 0.5 and 13% for x = 1. In C(6)H(5)COOH, proton exchange proceeded to about 82% for x = 0, ∼40% for x = 0.5, and ∼25% for x = 1. Similar proton-exchange trends were reported in H(2)O, where ion exchange occurs more readily for garnets with lower Li content in Li(5+x)Ba(x)La(3-x)Nb(2)O(12), that is, when excess Li ions preferentially reside in the tetrahedral sites of the garnet structure.

Extraction of alkyl methylphosphonic acids from aqueous samples using a conventional polymeric solid-phase extraction sorbent and a molecularly imprinted polymer.

The analysis of alkyl methylphosphonic acids (AMPAs) constitutes an important subject for verifying the compliance to the Chemical Weapons Convention (CWC). Indeed, alkyl methylphosphonic acids are the degradation products of V and G nerve agents such as VX, sarin or soman. Lowering the limits of detection of analytical methods for complex aqueous matrices implies the introduction of concentration and clean-up steps in the whole analytical process. Therefore a molecular imprinted polymer (MIP) has been previously developed for the selective extraction and the concentration of the alkyl methylphosphonic acids. Unfortunately, the selective retention process on this MIP has involved the development of hydrogen bonds and so does not allow the direct percolation of aqueous samples. A change of solvent is then necessary and can be performed using solid-phase extraction (SPE) with conventional non selective hydrophobic sorbents. Two polymeric sorbents, Oasis HLB and HR-P resins, were selected for their high specific surface area. The extraction recoveries obtained on both sorbents were compared and the Oasis HLB sorbent was further selected and used for the percolation of acidified aqueous samples. An optimised SPE procedure was then applied to concentrate an aqueous soil extract spiked with isobutyl methylphosphonic acid (iBMPA) and cyclopentyl methylphosphonic acid (cPMPA) that was further cleaned-up by passing through the MIP. The resulting LC-MS full scan chromatograms highlight the clean-up effect of the SPE-MIP association by the removal of the matrix substances and the preservation of 95% of the compounds of interest.