Pan AMPK Activation Protects Tubules in Rat Ischemic Acute Kidney Injury.

Acute Kidney Injury (AKI) is characterized by an abrupt decline in kidney function and has been associated with excess risks of death, kidney disease progression, and cardiovascular events. The kidney has a high energetic demand with mitochondrial health being essential to renal function and damaged mitochondria has been reported across AKI subtypes. 5' adenosine monophosphate-activated protein kinase (AMPK) activation preserves cellular energetics through improvement of mitochondrial function and biogenesis when ATP levels are low such as under ischemia-induced AKI. We developed a selective potent small molecule pan AMPK activator, compound 1, and tested its ability to increase AMPK activity and preserve kidney function during ischemia/reperfusion injury in rats. A single administration of 1 caused sustained activation of AMPK for at least 24 hours, protected against acute tubular necrosis, and reduced clinical markers of tubular injury such as NephroCheck and Fractional Excretion of Sodium (FENa). Reduction in plasma creatinine and increased Glomerular Filtration Rate (GFR) indicated preservation of kidney function. Surprisingly, we observed a strong diuretic effect of AMPK activation associated with natriuresis both with and without AKI. Our findings demonstrate that activation of AMPK leads to protection of tubular function under hypoxic/ischemic conditions which holds promise as a potential novel therapeutic approach for AKI. Significance Statement No approved pharmacological therapies currently exist for acute kidney injury. We developed Compound 1 which dose-dependently activated AMPK in the kidney and protected kidney function and tubules after ischemic renal injury in the rat. This was accompanied by natriuresis in injured as well as uninjured rats.

Validation of the Short Version (TLS-15) of the Triangular Love Scale (TLS-45) across 37 Languages.

Love is a phenomenon that occurs across the world and affects many aspects of human life, including the choice of, and process of bonding with, a romantic partner. Thus, developing a reliable and valid measure of love experiences is crucial. One of the most popular tools to quantify love is Sternberg's 45-item Triangular Love Scale (TLS-45), which measures three love components: intimacy, passion, and commitment. However, our literature review reveals that most studies (64%) use a broad variety of shortened versions of the TLS-45. Here, aiming to achieve scientific consensus and improve the reliability, comparability, and generalizability of results across studies, we developed a short version of the scale-the TLS-15-comprised of 15 items with 5-point, rather than 9-point, response scales. In Study 1 (N = 7,332), we re-analyzed secondary data from a large-scale multinational study that validated the original TLS-45 to establish whether the scale could be truncated. In Study 2 (N = 307), we provided evidence for the three-factor structure of the TLS-15 and its reliability. Study 3 (N = 413) confirmed convergent validity and test-retest stability of the TLS-15. Study 4 (N = 60,311) presented a large-scale validation across 37 linguistic versions of the TLS-15 on a cross-cultural sample spanning every continent of the globe. The overall results provide support for the reliability, validity, and cross-cultural invariance of the TLS-15, which can be used as a measure of love components-either separately or jointly as a three-factor measure.

Exploring Attitudes Toward "Sugar Relationships" Across 87 Countries: A Global Perspective on Exchanges of Resources for Sex and Companionship.

The current study investigates attitudes toward one form of sex for resources: the so-called sugar relationships, which often involve exchanges of resources for sex and/or companionship. The present study examined associations among attitudes toward sugar relationships and relevant variables (e.g., sex, sociosexuality, gender inequality, parasitic exposure) in 69,924 participants across 87 countries. Two self-report measures of Acceptance of Sugar Relationships (ASR) developed for younger companion providers (ASR-YWMS) and older resource providers (ASR-OMWS) were translated into 37 languages. We tested cross-sex and cross-linguistic construct equivalence, cross-cultural invariance in sex differences, and the importance of the hypothetical predictors of ASR. Both measures showed adequate psychometric properties in all languages (except the Persian version of ASR-YWMS). Results partially supported our hypotheses and were consistent with previous theoretical considerations and empirical evidence on human mating. For example, at the individual level, sociosexual orientation, traditional gender roles, and pathogen prevalence were significant predictors of both ASR-YWMS and ASR-OMWS. At the country level, gender inequality and parasite stress positively predicted the ASR-YWMS. However, being a woman negatively predicted the ASR-OMWS, but positively predicted the ASR-YWMS. At country-level, ingroup favoritism and parasite stress positively predicted the ASR-OMWS. Furthermore, significant cross-subregional differences were found in the openness to sugar relationships (both ASR-YWMS and ASR-OMWS scores) across subregions. Finally, significant differences were found between ASR-YWMS and ASR-OMWS when compared in each subregion. The ASR-YWMS was significantly higher than the ASR-OMWS in all subregions, except for Northern Africa and Western Asia.

N-acylphosphatidylethanolamine, a gut- derived circulating factor induced by fat ingestion, inhibits food intake.

N-acylphosphatidylethanolamines (NAPEs) are a relatively abundant group of plasma lipids of unknown physiological significance. Here, we show that NAPEs are secreted into circulation from the small intestine in response to ingested fat and that systemic administration of the most abundant circulating NAPE, at physiologic doses, decreases food intake in rats without causing conditioned taste aversion. Furthermore, (14)C-radiolabeled NAPE enters the brain and is particularly concentrated in the hypothalamus, and intracerebroventricular infusions of nanomolar amounts of NAPE reduce food intake, collectively suggesting that its effects may be mediated through direct interactions with the central nervous system. Finally, chronic NAPE infusion results in a reduction of both food intake and body weight, suggesting that NAPE and long-acting NAPE analogs may be novel therapeutic targets for the treatment of obesity.

A Slim Majority: The Influence of Sex Ratio on Women's Body Dissatisfaction and Weight Loss Motivations.

The current investigation examined whether women's perceptions of the sex ratio (ratio of women to men) in the local population influence their body dissatisfaction and weight loss motivations. A higher ratio of women to men in a given population signifies a relative abundance of same-sex mating competitors, intensifying female intrasexual competition. Five studies (N = 1,776) tested the hypotheses that women's perceptions of a female-skewed sex ratio would correspond to increased feelings of intrasexual competitiveness and perceptions of unfavorable mating prospects, which would, in turn, be associated with heightened body dissatisfaction and weight loss motivations. Among university and community women (Studies 1and 2), perceptions of a female-skewed sex ratio corresponded to greater intrasexual competitiveness, increased body dissatisfaction, and increased dieting inclinations. Among single women, assessments of a female-skewed sex ratio corresponded to perceptions of unfavorable mating prospects, increased romantic pressure to alter their appearance, and higher body dissatisfaction (Study 3). Studies 4 and 5 experimentally manipulated perceived sex ratio. Women in the female-skewed condition felt less satisfied with their weights and shapes, but only if they believed the manipulation (Study 4). In Study 5, using a within-subjects design, women who evaluated a male-skewed (vs. female-skewed) dating profile array subsequently desired to lose less weight. Findings suggest women's perceptions of their social environments may contribute to body image and dieting motivations.

Debunking Lesbian Bed Death: Using Coarsened Exact Matching to Compare Sexual Practices and Satisfaction of Lesbian and Heterosexual Women.

The current study examined the prevalence and correlates of over 50 sexual practices in a national survey of heterosexual and lesbian women in relationships. Coarsened exact matching was used to create comparable samples of heterosexual (n = 2510) and lesbian (n = 283) women on six demographic factors, including relationship length. Heterosexual and lesbian women were equally likely to be sexually satisfied (66% heterosexual women vs. 68% lesbian women). Compared to heterosexuals, lesbians were more likely to report having sex 0-1 times per month (11% vs. 23%) and were less likely to report having sex greater than once per month (89% vs. 77%). Among women who had been in relationships for longer than 5 years, heterosexual women were less likely than lesbian women to report having sex 0-1 times per month (15%; 42%). This steeper drop in sexual frequency among lesbian women than heterosexual women has pejoratively been labeled lesbian bed death. Rather than accept the label "lesbian bed death" as characterizing these sexual relationships, we turn our attention to what we call lesbian bed intimacies: the myriad ways that lesbian women incorporate behaviors promoting emotional connection, romance, and mood setting, as well as relying on a wide variety of specific sexual acts (e.g., use of sex toys) and sexual communication. Compared to heterosexual women, lesbian women were more likely to usually to always receive oral sex during sex in the past month (28%; 47%) and to use sex toys in the past year (40%; 62%). In their last sexual encounter, lesbian women were more likely to say "I love you" (67%; 80%), have sex longer than 30 min (48%; 72%), and engage in gentle kissing (80%; 92%). These intimacies likely help explain why sexual satisfaction was similar in these groups despite notable differences in sexual frequency.

Comparing internalization of appearance ideals and appearance-related pressures among women from the United States, Italy, England, and Australia.

Researchers have observed variation in levels of body image disturbance and eating pathology among women from different Western countries. Examination of cross-cultural differences in the established risk factors (i.e., thin-ideal internalization, muscular-ideal internalization, and appearance pressures from family, peers, and media) for negative outcomes may help to elucidate the prominence of specific risk factors within a given Western society and guide associated interventions. Women from the United States (US), Italy, England, and Australia completed the Sociocultural Attitudes Towards Appearance Questionnaire-4 (SATAQ-4). Analysis of covariance controlling for age and BMI indicated significant cross-country differences for all SATAQ-4 subscales. Results typically indicated higher levels of appearance-ideal internalization and appearance pressures in the US and lower levels in Italy; however, associated effect sizes were generally small. A medium effect of country was observed for peer-appearance pressures, which were highest in the US compared with all other countries. Repeated-measures analysis of variance and paired samples t tests conducted within each country identified thin-ideal internalization and media appearance pressures as the predominant risk factors for all four countries. Overall, findings suggest more cross-country similarities than differences, and highlight the importance of delivering interventions to address thin-ideal internalization and media appearance pressures among women from Western backgrounds.Level of evidence Descriptive study, Level V.

Identifying a male clinical cutoff on the Eating Disorder Examination-Questionnaire (EDE-Q).

OBJECTIVE: Evidence suggests that eating disorders (EDs) may be under-detected in males. Commonly used measures of EDs such as the Eating Disorder Examination-Questionnaire (EDE-Q) were initially developed within female samples, raising concern regarding the extent to which these instruments may be appropriate for detecting EDs in males. The current study used receiver operating characteristic curve analysis to (a) examine the accuracy of the EDE-Q global score in correctly classifying males with and without clinically significant ED pathology, and (b) establish the optimal EDE-Q global clinical cutoff for males. METHOD: Participants were a clinical sample of 245 male ED patients and a control sample of 205 male undergraduates. RESULTS: Eating Disorder Examination-Questionnaire global scores demonstrated moderate-high accuracy in predicting ED status (area under the curve = 0.85, 95% CI: 0.82-0.89). The optimal cutoff of 1.68 yielded a sensitivity of 0.77 and specificity of 0.77. DISCUSSION: Overall, results provide preliminary support for the discriminant validity of EDE-Q scores among males. However, concerns remain regarding the measure's ability to comprehensively assess domains of disordered eating most relevant to males. Therefore, careful attention to the possibility for measurement bias and continued evaluation of the scale in males is encouraged.

Differences in Orgasm Frequency Among Gay, Lesbian, Bisexual, and Heterosexual Men and Women in a U.S. National Sample.

There is a notable gap between heterosexual men and women in frequency of orgasm during sex. Little is known, however, about sexual orientation differences in orgasm frequency. We examined how over 30 different traits or behaviors were associated with frequency of orgasm when sexually intimate during the past month. We analyzed a large US sample of adults (N = 52,588) who identified as heterosexual men (n = 26,032), gay men (n = 452), bisexual men (n = 550), lesbian women (n = 340), bisexual women (n = 1112), and heterosexual women (n = 24,102). Heterosexual men were most likely to say they usually-always orgasmed when sexually intimate (95%), followed by gay men (89%), bisexual men (88%), lesbian women (86%), bisexual women (66%), and heterosexual women (65%). Compared to women who orgasmed less frequently, women who orgasmed more frequently were more likely to: receive more oral sex, have longer duration of last sex, be more satisfied with their relationship, ask for what they want in bed, praise their partner for something they did in bed, call/email to tease about doing something sexual, wear sexy lingerie, try new sexual positions, anal stimulation, act out fantasies, incorporate sexy talk, and express love during sex. Women were more likely to orgasm if their last sexual encounter included deep kissing, manual genital stimulation, and/or oral sex in addition to vaginal intercourse. We consider sociocultural and evolutionary explanations for these orgasm gaps. The results suggest a variety of behaviors couples can try to increase orgasm frequency.

Stable isotope labeling by essential nutrients in cell culture (SILEC) for accurate measurement of nicotinamide adenine dinucleotide metabolism.

Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are conserved metabolic cofactors that mediate reduction-oxidation (redox) reactions throughout all domains of life. The diversity of synthetic routes and cellular processes involving the transfer of reducing equivalents to and from these cofactors makes the accurate quantitation and metabolic tracing of NAD(H) and NADP(H) of broad interest. However, current analytical techniques typically rely on standard curves that do not incorporate confounding effects of the sample matrix. We utilized the essential requirement of niacin and tryptophan for NAD synthesis in mammalian cells to devise a stable isotope labeling by essential nutrients in cell culture (SILEC) method for efficient labeling of intracellular NAD(H) and NADP(H) pools. Coupling this approach with detection by liquid chromatography-high resolution mass spectrometry (LC-HRMS), we demonstrate the utility of incorporating a [13C315N1]-nicotinamide moiety into a library of NAD-derived metabolites for use as internal standards in matrixed samples. Using a two-label system incorporating [13C315N1]-nicotinamide and [13C11]-tryptophan, we quantify the relative contribution of salvage and de novo NAD synthesis, respectively, in S. cerevisiae and HepG2 human hepatocellular carcinoma cells under basal conditions. As a further proof-of-principle, we demonstrate an improvement in the linear range for quantification of NAD and apply this method to analysis of NAD(H) in mouse liver. This method demonstrates the generalizability of SILEC, and provides a simple method for generating a library of stable isotope labeled internal standards for quantifying and tracing the metabolism of cellular and tissue NAD(H) and NADP(H).

Imaging Redox State in Mouse Muscles of Different Ages.

Aging is the greatest risk factor for many diseases. Intracellular concentrations of nicotinamide adenine dinucleotide (NAD+) and the NAD+-coupled redox state have been proposed to moderate many aging-related processes, yet the specific mechanisms remain unclear. The concentration of NAD+ falls with age in skeletal muscle, yet there is no consensus on whether aging will increase or decrease the redox potential of NAD+/NADH. Oxidized flavin groups (Fp) (e.g. FAD, i.e., flavin adenine dinucleotide, contained in flavoproteins) and NADH are intrinsic fluorescent indicators of oxidation and reduction status of tissue, respectively. The redox ratio, i.e., the ratio of Fp to NADH, may be a surrogate indicator of the NAD+/NADH redox potential. In this study we used the Chance redox scanner (NADH/Fp fluorescence imaging at low temperature) to investigate the effect of aging on the redox state of mitochondria in skeletal muscles. The results showed that there are borderline significant differences in nominal concentrations of Fp and NADH, but not in the redox ratio s when comparing 3.5-month and 13-month old muscles of mice (n = 6). It may be necessary to increase the number of muscle samples and study mice of more advanced age.

Increasing NAD synthesis in muscle via nicotinamide phosphoribosyltransferase is not sufficient to promote oxidative metabolism.

The NAD biosynthetic precursors nicotinamide mononucleotide and nicotinamide riboside are reported to confer resistance to metabolic defects induced by high fat feeding in part by promoting oxidative metabolism in skeletal muscle. Similar effects are obtained by germ line deletion of major NAD-consuming enzymes, suggesting that the bioavailability of NAD is limiting for maximal oxidative capacity. However, because of their systemic nature, the degree to which these interventions exert cell- or tissue-autonomous effects is unclear. Here, we report a tissue-specific approach to increase NAD biosynthesis only in muscle by overexpressing nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway that converts nicotinamide to NAD (mNAMPT mice). These mice display a ∼50% increase in skeletal muscle NAD levels, comparable with the effects of dietary NAD precursors, exercise regimens, or loss of poly(ADP-ribose) polymerases yet surprisingly do not exhibit changes in muscle mitochondrial biogenesis or mitochondrial function and are equally susceptible to the metabolic consequences of high fat feeding. We further report that chronic elevation of muscle NAD in vivo does not perturb the NAD/NADH redox ratio. These studies reveal for the first time the metabolic effects of tissue-specific increases in NAD synthesis and suggest that critical sites of action for supplemental NAD precursors reside outside of the heart and skeletal muscle.

Upset Over Sexual versus Emotional Infidelity Among Gay, Lesbian, Bisexual, and Heterosexual Adults.

One hypothesis derived from evolutionary perspectives is that men are more upset than women by sexual infidelity and women are more upset than men by emotional infidelity. The proposed explanation is that men, in contrast to women, face the risk of unwittingly investing in genetically unrelated offspring. Most studies, however, have relied on small college or community samples of heterosexual participants. We examined upset over sexual versus emotional jealousy among 63,894 gay, lesbian, bisexual, and heterosexual participants. Participants imagined which would upset them more: their partners having sex with someone else (but not falling in love with them) or their partners falling in love with someone else (but not having sex with them). Consistent with this evolutionary perspective, heterosexual men were more likely than heterosexual women to be upset by sexual infidelity (54 vs. 35 %) and less likely than heterosexual women to be upset by emotional infidelity (46 vs. 65 %). This gender difference emerged across age groups, income levels, history of being cheated on, history of being unfaithful, relationship type, and length. The gender difference, however, was limited to heterosexual participants. Bisexual men and women did not differ significantly from each other in upset over sexual infidelity (30 vs. 27 %), regardless of whether they were currently dating a man (35 vs. 29 %) or woman (28 vs. 20 %). Gay men and lesbian women also did not differ (32 vs. 34 %). The findings present strong evidence that a gender difference exists in a broad sample of U.S. adults, but only among heterosexuals.

Absolute lymphocyte count recovery after allogeneic hematopoietic stem cell transplantation predicts clinical outcome.

Immune reconstitution is critical for clinical outcome after allogeneic hematopoietic stem cell transplantation (HSCT). To determine the impact of absolute lymphocyte count (ALC) recovery on clinical outcomes, we conducted a retrospective study of 1109 adult patients who underwent a first allogeneic HSCT from 2003 through 2009, excluding patients who died or relapsed before day 30. The median age was 51 years (range, 18 to 74) with 52% undergoing reduced-intensity conditioning and 48% undergoing myeloablative conditioning HSCT with T cell-replete peripheral blood stem cells (93.7%) or marrow (6.4%) grafts. The median follow-up time was 6 years. To determine the threshold value of ALC for survival, the entire cohort was randomly split into a training set and a validation set in a 1:1 ratio, and then a restricted cubic spline smoothing method was applied to obtain relative hazard estimates of the relationship between ALC at 1 month and log hazard of progression-free survival (PFS). Based on this approach, ALC was categorized as ≤.2 × 10(9) cells/L (low) or >.2 × 10(9) cells/L. For patients with low ALC at 1, 2, or 3 months after HSCT, the overall survival (OS) (P ≤ .0001) and PFS (P ≤ .0002) were significantly lower and nonrelapse mortality (NRM) (P ≤ .002) was significantly higher compared with patients with ALC > .2 × 10(9) cells/L at each time point. When patients who had low ALC at 1, 2, or 3 months after HSCT were grouped together and compared, their outcomes were inferior to those of patients who had ALC > .2 × 10(9) cells/L at 1, 2, and 3 months after HSCT: the 5-year OS for patients with low ALC was 28% versus 46% for patients with ALC > .2 × 10(9) cells/L, P < .0001; the 5-year PFS was 21% versus 39%, P < .0001, respectively and 5-year NRM was 40% versus 18%, P < .0001, respectively. This result remained consistent when other prognostic factors, including occurrence of grade II to IV acute graft-versus-host disease (GVHD), were adjusted for in multivariable Cox models stratified by conditioning intensity: hazard ratio (HR) for OS: 1.52; P ≤ .0001; for PFS: 1.42; P = .0008; and for NRM: 2.4 P < .0001 for patients with low ALC. Low ALC was not significantly associated with relapse (HR, 1.01; P = .92) in the multivariable model. Low ALC early after HSCT is an independent risk factor for increased NRM and poor survival independent of grade II to IV acute GVHD.

White blood cell recovery after allogeneic hematopoietic cell transplantation predicts clinical outcome.

To determine whether outcome after allogeneic hematopoietic cell transplantation (HCT) could be estimated by using peripheral white blood cell count (WBC) as a metric that integrates several aspects of HCT recovery, we conducted a retrospective study of 1,109 adult patients who underwent first allogeneic HCT from 2003 through 2009. WBC at 1-3 months after HCT was categorized as low (<2), normal (2-10), and high (>10 × 10(9) cells/L). Overall survival (OS) and progression-free survival (PFS) were lower for patients with low or high WBC at 1-3 months after HCT (P < 0.0001). We developed a predictive three-group risk model based on the pattern of WBC recovery early after HCT. Five-year OS was 47, 30, and 15% (P < 0.0001) and 5-year PFS was 39, 22, and 14% for patients in the three different risk groups (P < 0.0001). The pattern of WBC recovery early after HCT provides prognostic information for relapse, nonrelapse mortality, progression-free survival, and overall survival. A scoring system based on the trajectory of the WBC in the first 3 months after HCT can effectively stratify patients into three groups with different PFS and OS. If validated, this system could be useful in the clinical management of patients after HCT, and to stratify patients enrolled on HCT clinical trials.

Women Who Experience More Affectionate Touch Report Better Body Satisfaction and Relationship Outcomes.

Affectionate touch (e.g. hugging, handholding) is an essential component of many intimate relationships and is a primary contributor to overall relationship satisfaction as well as sexual satisfaction. Affectionate touch is understood to be a form of non-verbal communication in which the giver is expressing positive feelings toward the receiver. Here, we propose that affectionate touch also positively impacts receivers' body satisfaction, because affectionate touch is a positive message communicated toward the receiver's body. In a cross-sectional sample of romantically partnered women (N = 1,156), we assessed the association between affectionate touch frequency and body satisfaction. We also investigated whether affectionate touch is associated with relationship/sexual satisfaction in part because touch helps to improve women's evaluations of their own bodies. Our results showed that body satisfaction was a significant, partial mediator and a valid path through which affectionate touch shapes relationship quality. Receiving affectionate touch could bolster relationship satisfaction and self-perceptions among women. Given the prevalence of body dissatisfaction amongst women, these results suggest that the underexplored associations between affectionate touch and body satisfaction may have significant impacts on a wide array of future empirical and applied research trajectories.

Sexual regret: evidence for evolved sex differences.

Regret and anticipated regret enhance decision quality by helping people avoid making and repeating mistakes. Some of people's most intense regrets concern sexual decisions. We hypothesized evolved sex differences in women's and men's experiences of sexual regret. Because of women's higher obligatory costs of reproduction throughout evolutionary history, we hypothesized that sexual actions, particularly those involving casual sex, would be regretted more intensely by women than by men. In contrast, because missed sexual opportunities historically carried higher reproductive fitness costs for men than for women, we hypothesized that poorly chosen sexual inactions would be regretted more by men than by women. Across three studies (Ns = 200, 395, and 24,230), we tested these hypotheses using free responses, written scenarios, detailed checklists, and Internet sampling to achieve participant diversity, including diversity in sexual orientation. Across all data sources, results supported predicted psychological sex differences and these differences were localized in casual sex contexts. These findings are consistent with the notion that the psychology of sexual regret was shaped by recurrent sex differences in selection pressures operating over deep time.