Circadian Influences on Myocardial Ischemia-Reperfusion Injury and Heart Failure.

The impact of circadian rhythms on cardiovascular function and disease development is well established, with numerous studies in genetically modified animals emphasizing the circadian molecular clock's significance in the pathogenesis and pathophysiology of myocardial ischemia and heart failure progression. However, translational preclinical studies targeting the heart's circadian biology are just now emerging and are leading to the development of a novel field of medicine termed circadian medicine. In this review, we explore circadian molecular mechanisms and novel therapies, including (1) intense light, (2) small molecules modulating the circadian mechanism, and (3) chronotherapies such as cardiovascular drugs and meal timings. These promise significant clinical translation in circadian medicine for cardiovascular disease. (4) Additionally, we address the differential functioning of the circadian mechanism in males versus females, emphasizing the consideration of biological sex, gender, and aging in circadian therapies for cardiovascular disease.

Effects of stress management interventions on heart rate variability in adults with cardiovascular disease: a systematic review and meta-analysis.

Meta-analysis was used to investigate the potential benefits of stress management interventions (SMIs) on vagally-mediated heart rate variability (HRV) in adults with cardiovascular disease. Electronic bibliographic databases were searched through August 2022. Randomized controlled trials and quasi-experimental studies assessing effects of SMIs on HRV were included. Methodological quality was assessed with a standardized checklist. A pooled effect size was calculated for vagally-mediated HRV indices (standard deviation of normal-to-normal intervals, root mean square of the successive differences, and high frequency power) using random effects models. Fourteen studies (1202 participants, Mage: 59 ± 6.25 years; 25% ± 16% women; 61% ± 22% White) were included. Ten studies (11 effects) reported short-term HRV assessment; a small between-group difference emerged for vagally-mediated HRV (d+ = .27, 95% confidence interval [CI] 0.01-0.52, k = 11). Most interventions examined biofeedback; these studies yielded a small between-group difference on vagally-mediated HRV (d+ = 0.31, 95% CI 0.09-0.53, k = 7, Q [6] = 3.82, p = .70, I2 = 11%). This is the first systematic examination of the effect of SMIs on HRV in adults with CVD. Findings suggest a small effect of SMIs on vagally-mediated HRV, with biofeedback likely driving the effect. More research is required to fully understand whether this benefit on vagally-mediated HRV applies to other SMIs.

A randomized comparison of online mindfulness-based group sex therapy vs supportive group sex education to address sexual dysfunction in breast cancer survivors.

BACKGROUND: Sexual difficulties and vaginal pain are common following treatment for breast cancer. AIM: The goal of this study was to evaluate an online mindfulness-based group sex therapy vs an online supportive sex education group therapy to address these sexual difficulties. METHODS: Breast cancer survivors (n = 118) were randomized to 1 of the 2 arms; 116 provided informed consent and completed the time 1 assessment. Treatment included 8 weekly 2-hour online group sessions. Those randomized to the mindfulness group completed daily mindfulness exercises, and those in the comparison arm read and completed exercises pertaining to sex education. OUTCOMES: Assessments were repeated at posttreatment and 6 months after the completion of the group. RESULTS: There was a main effect of treatment on primary endpoints of sexual desire, sexual distress, and vaginal pain, with all outcomes showing significant improvements, with no differential impact by treatment arm. Secondary endpoints of interoceptive awareness, mindfulness, and rumination about sex also significantly improved with both treatments, with no group-by-time interaction. CONCLUSION: Both mindfulness-based sex therapy and supportive sex education delivered in group format online are effective for improving many facets of sexual function, vaginal pain, rumination, mindfulness, and interoceptive awareness in breast cancer survivors. STRENGTHS AND LIMITATIONS: We used a randomized methodology. Future studies should seek to diversify participants. CLINICAL IMPLICATIONS: These findings highlight the need to offer similar treatments to more breast cancer survivors immediately after and in the years following cancer treatment as a means of improving survivorship quality of life.

Effects of Group Mindfulness-Based Cognitive Therapy versus Supportive Sex Education on Sexual Concordance and Sexual Response Among Women with Sexual Interest/Arousal Disorder.

Low interest in sexual activity and impaired sexual response are among women's most frequent sexual concerns. Mindfulness-based treatments improve low sexual desire and arousal and associated distress. One theorized mechanism of change is the cultivation of increased mind-body awareness via greater concordance between psychological and physiological components of sexual response. We examined sexual psychophysiology data from 148 cisgender women randomized to receive mindfulness-based cognitive therapy (MCBT: n = 70) or supportive sex education (STEP: n = 78) over eight weekly group sessions. Women completed in-lab assessments of subjective, affective, and genital sexual responses to an erotic film pre- and post-treatment, and at 6- and 12-month follow-ups. Both groups showed positive changes in sexual and affective responses, but these were generally more pronounced for MBCT. MCBT increased sexual concordance to a greater degree, and gains in sexual concordance predicted improvements in sexual distress throughout treatment.

A Systems Approach for Assessing Low Back Pain Care Quality in Veterans Health Administration Chiropractic Visits: A Cross-Sectional Analysis.

OBJECTIVE: The purpose of this study was to explore a systemwide process for assessing components of low back pain (LBP) care quality in Veterans Health Administration (VHA) chiropractic visits using electronic health record (EHR) data. METHODS: We performed a cross-sectional quality improvement project. We randomly sampled 1000 on-station VHA chiropractic initial visits occurring from October 1, 2017, to September 30, 2018, for patients with no such visits within the prior 12 months. Characteristics of LBP visits were extracted from VHA national EHR data via structured data queries and manual chart review. We developed quality indicators for history and/or examination and treatment procedures using previously published literature and calculated frequencies of visits meeting these indicators. Visits meeting our history and/or examination and treatment indicators were classified as "high-quality" visits. We performed a regression analysis to assess associations between demographic/clinical characteristics and visits meeting our quality criteria. RESULTS: There were 592 LBP visits identified. Medical history, physical examination, and neurologic examination were documented in 76%, 77%, and 63% of all LBP visits, respectively. Recommended treatments, such as any manipulation, disease-specific education/advice, and therapeutic exercise, occurred in 75%, 69%, and 40% of chronic visits (n = 383), respectively. In acute/subacute visits (n = 37), any manipulation (92%), manual soft tissue therapy (57%), and disease-specific advice/education (54%) occurred most frequently. Female patients and those with a neck pain comorbid diagnosis were significantly less likely to have a "high-quality" visit, while other regression associations were non-significant. CONCLUSION: This study explored a systemwide process for assessing components of care quality in VHA chiropractic visits for LBP. These results produced a potential framework for uniform assessment of care quality in VHA chiropractic visits for LBP and highlight potential areas for improvements in LBP care quality assessments.

Benefits and Harms of Standard Versus Reduced-Dose Direct Oral Anticoagulant Therapy for Older Adults With Multiple Morbidities and Atrial Fibrillation.

Background Dose reduction of direct oral anticoagulant (DOAC) medications is inconsistently applied to older adults with multiple morbidities, potentially due to perceived harms and unknown benefits of standard dosing. Methods and Results Using 2013 to 2017 US Medicare claims linked to Minimum Data Set records, we conducted a retrospective cohort study. We identified DOAC initiators (apixaban, dabigatran, rivaroxaban) aged ≥65 years with nonvalvular atrial fibrillation residing in a nursing home. We estimated inverse-probability of treatment weights for DOAC dose using propensity scores. We examined safety (hospitalization for major bleeding) and effectiveness outcomes (all-cause mortality, thrombosis [myocardial infarction, stroke, systemic embolism, venous thromboembolism]). We estimated hazard ratios (HRs) and 95% CIs using cause-specific hazard-regression models. Of 21 878 DOAC initiators, 48% received reduced dosing. The mean age of residents was 82.0 years, 66% were female, and 31% had moderate/severe cognitive impairment. After estimating inverse-probability of treatment weights, standard dosing was associated with a higher rate of bleeding (HR, 1.18 [95% CI, 1.03-1.37]; 9.4 versus 8.0 events per 100 person-years). Standard-dose therapy was associated with the highest rates of bleeding among those aged >80 years (9.1 versus 6.7 events per 100 person-years) and with a body mass index <30 kg/m2 (9.4 versus 7.4 events per 100 person-years). There was no association of dosing with mortality (HR, 0.99 [95% CI, 0.96-1.06]) or thrombotic events (HR, 1.16 [95% CI, 0.96-1.41]). Conclusions In this nationwide study of nursing home residents with nonvalvular atrial fibrillation, we found a higher rate of bleeding and little difference in effectiveness of standard versus reduced-dose DOAC treatment. Our results support the use of reduced-dose DOACs for many older adults with multiple morbidities.

Differing Experiences of Nutrition Care During Treatment Among Oncology Nurses, Providers, and Patients.

BACKGROUND: Provision of nutrition care for patients with cancer represents a key component of holistic oncology care. However, information is limited about the use and perceptions of registered dietitian-led nutrition care in the oncology setting. OBJECTIVES: This study aimed to better understand the experiences and expectations of patients and healthcare workers regarding nutrition care during outpatient cancer treatment. METHODS: Oncology care team members (N = 55) and patients (N = 90) completed a survey about their knowledge of and interest in nutrition care. A subset of participants completed semistructured interviews to capture experiences with and perspectives on nutrition care practices. FINDINGS: The majority of patients (n = 73) reported experiencing at least one nutrition impact symptom, but only 14 indicated that they frequently discussed nutrition during provider visits. In addition, 40 oncology care team members indicated frequently discussing nutrition at visits, although 13 were unaware of local nutrition resources.

History of Sexual Assault as a Predictor of Response to a Self-Guided Online Program for Sexual Desire and Arousal Difficulties in Women.

Sexual Interest/Arousal Disorder (distressing, long-lasting impairments in sexual desire and/or arousal) is common in women, but few have access to efficacious psychotherapies, including cognitive-behavioral therapy (CBT) and mindfulness-based therapy (MBT). eSense, an online program meant to maximize treatment access, has been shown to be a feasible, satisfactory, and potentially efficacious intervention. However, subpopulations such as sexual assault survivors may find the program less usable or efficacious. The current study compared women with and without a history of sexual assault (SA) regarding their ability to use and benefit from eSense. Forty-four women (22 with a history of SA; M age = 34.20 years) used eSense (CBT or MBT) and completed validated self-report scales of sexual function, sexual distress, treatment satisfaction, and homework compliance. A history of SA did not predict differences in attrition or changes in clinical outcomes. Exploratory analyses suggested that women with a history of SA reported slightly higher difficulty completing homework assignments, but also slightly higher treatment satisfaction. These preliminary results suggest that eSense may be usable and helpful for women with a history of SA. We discuss ways to maximize the acceptability and efficacy of online programs for women with a history of SA.

Enhancing circadian rhythms-the circadian MEGA bundle as novel approach to treat critical illness.

Circadian rhythms are essential to physiological homeostasis, but often disrupted in the intensive care unit (ICU) due to the absence of natural zeitgebers and exposure to treatments which affect circadian regulators. This is increasingly recognized as a contributor to morbidity and mortality across a variety of medical conditions including critical illness. Maintenance of circadian rhythms is particularly relevant to critically ill patients, who are restricted not only to the ICU environment but often bed bound. Circadian rhythms have been evaluated in several ICU studies, but effective therapies to maintain, restore, or amplify circadian rhythms have not been fully established yet. Circadian entrainment and circadian amplitude enhancement are integral to patients' overall health and well-being, and likely even more important during response to and recovery from critical illness. In fact, studies have shown that enhancing the amplitude of circadian cycles has significant beneficial effects on health and wellbeing. In this review, we discuss up-to-date literature on novel circadian mechanism that could not only restore but enhance circadian rhythms in critical illness by using a MEGA bundle consisting of intense light therapy each morning, cyclic nutrition support, timed physical therapy, nighttime melatonin administration, morning administration of circadian rhythm amplitude enhancers, cyclic temperature control and a nocturnal sleep hygiene bundle.

A virtual, group-based mindfulness intervention for midlife and older women with low libido lowers sexual distress in a randomized controlled pilot study.

BACKGROUND: Distressing low libido is common among women and has significant negative impacts; mindfulness has shown promise to increase sexual desire in women with low libido, but existing interventions are not tailored to midlife and older women. AIM: We adapted a mindfulness intervention to meet the needs of this population and conducted a pilot randomized controlled trial to assess feasibility and acceptability. METHODS: Women aged ≥45 years with low libido were randomized to the mindfulness intervention or an education group that met over videoconferencing. The intervention included mindfulness instruction and practice, group discussion, and education on sexuality and aging. The education group included general information on menopause and health. OUTCOMES: We defined feasibility by the number of screened women who enrolled and completed their group. We defined acceptability as satisfaction with the group and likelihood of recommending it to another woman with low libido. We assessed sexual function (Female Sexual Function Index) and sexual distress (Female Sexual Distress Scale-Revised) at 6 weeks postconclusion. RESULTS: Of 81 women screened, 31 were randomized to mindfulness and 30 to education. Eighteen women in the intervention group and 23 in the control group attended at least 1 session. Time conflict was the main reason for nonattendance. Of the 41 women who started attending groups, 37 (90%) attended at least 5 sessions. In the mindfulness group, 73% of women were very or extremely satisfied. Women in the mindfulness group were more likely to recommend it to another person with low libido as compared with those in the education group (P = .031); 67% said that they would probably or definitely recommend it. There were no significant changes in sexual function in either group (mean Female Sexual Function Index score, 22.6 to 18.6 [P = .101] with mindfulness and 21.2 to 19.7 [P = .537] with education). Women in the mindfulness group had significant improvements in sexual distress (mean Female Sexual Distress Scale-Revised score, 27.1 to 19.7; P = .021) while women in the education group did not (19.0 to 15.8; P = .062). CLINICAL IMPLICATIONS: Mindfulness may reduce sexual distress in older women with low libido. STRENGTHS AND LIMITATIONS: This is the first trial testing mindfulness for midlife and older women with low libido. CONCLUSION: A virtual mindfulness intervention for midlife and older women with low libido is feasible and acceptable and appears to improve sexual distress as compared with an education control; these findings provide data that can be used to design a larger clinical trial.

"Don't Turn a Blind Eye": An Instruction for Supporting Meaningful Conversations About Gender-Based Violence During Perinatal Care.

BACKGROUND AND PURPOSE: Evidence suggests that Gender-based violence (GBV) is prevalent throughout the perinatal period. Women during this time have frequent contact with healthcare providers (HCPs), and there are many opportunities that HCPs can identify GBV and support women by early intervention during routine prenatal care. However, evidence shows that HCPs are still hesitant to address this issue. This study was conducted to explore the experiences of Survivors and HCPs on how to manage a meaningful conversation about GBV with survivors during perinatal care. METHODS: A thematic approach has been used in this qualitative study. RESULTS: Twenty-eight semi-structured interviews were conducted with survivors and HCPs. Three main themes emerged from the data analysis, including: "Knock gently on the door to enter the client's private world", "Show interest in clients' stories that are beyond their physical problems" and "Gradually and cautiously cross the hidden borders." CONCLUSION: HCPs play a pivotal role in identifying GBV and providing support for survivors, particularly during their perinatal period. However, initiating a conversation around this sensitive topic needs time, skill, and enough knowledge. Validating survivors' experiences, providing a private and safe atmosphere without judgment, and creating empathy could lead to more disclosure of GBV. To have a meaningful conversation, HCPs need to have a holistic approach toward care, show interest in clients' stories beyond their physical problems, and support clients who have shared sensitive information.

Psychological Treatment of Persistent Genital Arousal Disorder/Genitopelvic Dysesthesia Using an Integrative Approach.

Persistent genital arousal disorder/genitopelvic dysesthesia (PGAD/GPD) is characterized by persistent, unwanted physiological genital arousal (i.e., sensitivity, fullness, and/or swelling) in the absence of sexual excitement or desire which can persist for hours to days and causes significant impairment in psychosocial well-being (e.g., distress) and daily functioning. The etiology and course of PGAD/GPD is still relatively unknown and, unsurprisingly, there are not yet clear evidence-based treatment recommendations for those suffering from PGAD/GPD. We present the case of a 58-year-old woman with acquired persistent genital arousal disorder, which began in March 2020; she believed she developed PGAD/GPD due to a period of significant distress and anxiety related to the COVID-19 pandemic. After seeking medical diagnosis and treatment from multiple healthcare providers and trying a combination of pharmacological and medical treatment modalities, she presented for psychological treatment. An integrative therapy approach (3 assessment sessions, 11 treatment sessions), which included cognitive behavior therapy, distress tolerance and emotion regulation skills from dialectical behavior therapy, and mindfulness practice, was utilized. The patient reported improvements anecdotally (e.g., decreased impact on occupational and social functioning, greater self-compassion, less frequent and shorter duration of PGAD/GPD flare-ups, improved ability to cope with PGAD/GPD symptoms, and decreased need for sleeping medication) and on self-report measures (e.g., lower PGAD/GPD catastrophizing, lower anxiety and depression, and greater overall quality of life).We report the use of an integrative (i.e., psychoeducational, cognitive behavioral, dialectical behavioral, and mindfulness-based) intervention, which may be an effective psychological treatment for PGAD/GPD.

A randomized comparison of group mindfulness and group cognitive behavioral therapy vs control for couples after prostate cancer with sexual dysfunction.

BACKGROUND: Sexual dysfunction is the most common and most distressing consequence of prostate cancer (PCa) treatment and has been shown to directly affect the sexual function and quality of life of survivors' partners. There are currently no established therapies to treat the emotional and psychological burden that sexual issues impose on the couple after PCa. AIM: Our study examined the impact of 2 therapies-cognitive behavioral therapy (CBT) and mindfulness therapy-on sexual, relational, and psychological outcomes of PCa survivor and partner couples. METHODS: PCa survivors (n = 68) who self-reported current sexual problems after PCa treatments and their partners were randomized to 4 consecutive weeks of couples' mindfulness therapy, couples' CBT, or no treatment (control). OUTCOMES: Couples' sexual distress, survivors' sexual satisfaction, and couples' relationship satisfaction, quality of life, psychological symptoms (anxiety and depression), and trait mindfulness were measured at baseline, 6 weeks after treatment, and 6 months after treatment. RESULTS: Sexual distress and sexual satisfaction were significantly improved 6 weeks after the CBT and mindfulness interventions as compared with the control group, but only sexual distress remained significantly improved at 6 months. Relationship satisfaction decreased and more so for partners than survivors. There were increases in domains of quality of life for survivors vs their partners 6 months after treatments and an overall increase in general quality of life for couples 6 weeks after mindfulness. There were no significant changes in psychological symptoms and trait mindfulness. Qualitative analysis showed that the mindfulness intervention led to greater personal impact on couple intimacy after the study had ended. CLINICAL IMPLICATIONS: CBT and mindfulness can be effective treatments for helping couples adapt to and cope with changes to their sexual function after PCa treatments and could help improve the most common concern for PCa survivors-that is, couples' sexual intimacy-after cancer, if added to routine clinical care. STRENGTHS AND LIMITATIONS: We used established standardized treatment manuals and highly sensitive statistical methodology and accounted for covariable factors and moderators of primary outcomes. Due to difficulty in recruitment, we had a smaller control group than treatment, reducing our power to detect between-group differences. Our sample was mostly White, heterosexual, and affluent, thereby limiting the generalizability. CONCLUSION: This is the first randomized clinical trial to test and demonstrate benefits among PCa survivors and partners' sexual outcomes after CBT and mindfulness as compared with a nontreatment control group.

Feasibility and Acceptability of a Group-Based Mindfulness Intervention for Sexual Interest/Arousal Disorder Following Breast Cancer Treatment.

This study aimed to assess feasibility and preliminary efficacy of an 8-week Mindfulness-Based Cognitive Therapy (MBCT) group program to treat Sexual Interest/Arousal Disorder (SIAD) in women following breast cancer (BrCa) treatment. Thirty women participated, of whom 67% (n = 20) attended at least 6 of 8 group sessions. Feedback indicated the program was relevant and valuable; minor modifications were suggested to further address survivorship concerns. Results of pre-post questionnaires demonstrated significant improvements in sexual distress and sexual interest/desire, with large effect sizes. Results support the feasibility and preliminary efficacy of an 8-week MBCT program among women following breast cancer treatment.

Mindfulness and Sex Education for Sexual Interest/Arousal Disorder: Mediators and Moderators of Treatment Outcome.

Sexual Interest/Arousal Disorder (SIAD) is a common sexual dysfunction in women. Both mindfulness-based cognitive therapy (MBCT) plus psychoeducation and sex therapy, education, and support (STEP; which contains the same educational information as in the MBCT arm but also integrates supportive-expressive therapy), are effective. We tested mediators and moderators of improvements. Each treatment arm consisted of eight sessions delivered weekly, and participants completed measures online pre-treatment, immediately post-treatment, and at 6- and 12-month post-treatment. Depression, self-reported interoceptive awareness, self-compassion, self-criticism, and mindfulness were examined as mediators, and expectations for improvement as a moderator. Of 148 cisgender women who consented, 70 were randomized to the MBCT plus psychoeducation group (mean age 39.3 ± 13.2 yrs) and 78 to the STEP group (mean age 37.9 ± 12.2 yrs). Decreases in depression mediated decreases in sexual distress in the MBCT plus psychoeducation group only. Improvements in interoceptive awareness mediated changes in both sexual desire and arousal, and sexual distress, and to a greater degree after MBCT plus psychoeducation. Changes in self-compassion mediated changes in sexual desire and arousal only for the MBCT plus psychoeducation group and mediated changes in sexual distress in both groups. Reductions in self-criticism mediated improvements in sexual distress to a greater extent after MBCT plus psychoeducation. Changes in mindfulness predicted changes in desire and arousal, and distress only in the MBCT plus psychoeducation group. Expectations for improvement did not moderate any outcomes. The findings have implications for understanding common and potentially distinct pathways by which MBCT plus psychoeducation and supportive sex education improve symptoms of SIAD.

Incorporating Nutrition-Based Strategies into IBD Treatment.

PURPOSE OF REVIEW: Diet and nutrition have emerged as key factors in the development and course of inflammatory bowel disease (IBD), including the approach to therapy. We present an overview of evidence-based recommendations and recent research in dietary therapy and nutrition management for patients with IBD. RECENT FINDINGS: Patients with IBD should undergo a comprehensive nutrition assessment with the assistance of a registered dietitian (RD), including screening for micronutrient deficiencies. Multiple specialized whole foods and liquid formula diets have been evaluated as part of induction and maintenance therapy for IBD. Nutritional status should ideally be optimized in the perioperative setting as well. Nutritional issues are prevalent among IBD patients and should be addressed by a multidisciplinary team, tailored to each patient's disease type, severity and course, including response to medical therapy and need for surgical management, as well as relevant psychosocial considerations.

Clinical effects of proprioceptive thumb exercise for individuals with carpometacarpal joint osteoarthritis: A randomized controlled trial.

STUDY DESIGN: Randomized Control Trial. INTRODUCTION: Thumb CMC joint OA is a common diagnosis. Currently there is no evidence available to under if proprioceptive neuromuscular training is an effective intervention for this population. PURPOSE OF THE STUDY: To establish the effectiveness of a proprioceptive training program as a complementary therapy for patients with thumb CMC joint OA. METHODS: Standard conservative thumb CMC joint OA treatments were received by both the control (n = 26) and experimental groups (n = 26) for a period of 12 weeks. The experimental group received a proprioceptive training program during the same intervention period. Outcome measures included severity of pain with activity according to the numerical rating scale (NRS), QuickDASH, Canadian Occupational Performance Measure (COPM), and proprioception via joint position sense (JPS). RESULTS: Fifty-two females participated in the study. Both the experimental and control group made both clinically and statistically significant changes in the mean VAS and COPM scores over time. Only the experimental group achieved a statistically and clinically significant change in JPS error score over time. DISCUSSION: Experimental group achieved a statistically significant change in JPS over time in concordance with previous investigations. Changes in pain scores differed from prior investigations and the between-group comparison was not statistically significant. Changes in the Quick DASH was similar to previous findings. CONCLUSION: Proprioceptive training in addition to a traditional rehabilitation program decreased error scores on the joint position sense test.

PACAP-PAC1R modulates fear extinction via the ventromedial hypothalamus.

Exposure to traumatic stress can lead to fear dysregulation, which has been associated with posttraumatic stress disorder (PTSD). Previous work showed that a polymorphism in the PACAP-PAC1R (pituitary adenylate cyclase-activating polypeptide) system is associated with PTSD risk in women, and PACAP (ADCYAP1)-PAC1R (ADCYAP1R1) are highly expressed in the hypothalamus. Here, we show that female mice subjected to acute stress immobilization (IMO) have fear extinction impairments related to Adcyap1 and Adcyap1r1 mRNA upregulation in the hypothalamus, PACAP-c-Fos downregulation in the Medial Amygdala (MeA), and PACAP-FosB/ΔFosB upregulation in the Ventromedial Hypothalamus dorsomedial part (VMHdm). DREADD-mediated inhibition of MeA neurons projecting to the VMHdm during IMO rescues both PACAP upregulation in VMHdm and the fear extinction impairment. We also found that women with the risk genotype of ADCYAP1R1 rs2267735 polymorphism have impaired fear extinction.

Both G protein-coupled and immunoreceptor tyrosine-based activation motif receptors mediate venous thrombosis in mice.

Platelets are critical in hemostasis and a major contributor to arterial thrombosis (AT). (Pre)clinical studies suggest platelets also contribute to venous thrombosis (VT), but the mechanisms are largely unknown. We hypothesized that in VT, platelets use signaling machinery distinct from AT. Here we aimed to characterize the contributions of platelet G protein-coupled (GPCR) and immunoreceptor tyrosine-based activation motif (ITAM) receptor signaling to VT. Wild-type (WT) and transgenic mice were treated with inhibitors to selectively inhibit platelet-signaling pathways: ITAM-CLEC2 (Clec2mKO), glycoprotein VI (JAQ1 antibody), and Bruton's tyrosine kinase (ibrutinib); GPCR-cyclooxygenase 1 (aspirin); and P2Y12 (clopidogrel). VT was induced by inferior vena cava stenosis. Thrombin generation in platelet-rich plasma and whole-blood clot formation were studied ex vivo. Intravital microscopy was used to study platelet-leukocyte interactions after flow restriction. Thrombus weights were reduced in WT mice treated with high-dose aspirin + clopidogrel (dual antiplatelet therapy [DAPT]) but not in mice treated with either inhibitor alone or low-dose DAPT. Similarly, thrombus weights were reduced in mice with impaired ITAM signaling (Clec2mKO + JAQ1; WT + ibrutinib) but not in Clec2mKO or WT + JAQ1 mice. Both aspirin and clopidogrel, but not ibrutinib, protected mice from FeCl3-induced AT. Thrombin generation and clot formation were normal in blood from high-dose DAPT- or ibrutinib-treated mice; however, platelet adhesion and platelet-neutrophil aggregate formation at the vein wall were reduced in mice treated with high-dose DAPT or ibrutinib. In summary, VT initiation requires platelet activation via GPCRs and ITAM receptors. Strong inhibition of either signaling pathway reduces VT in mice.

Feasibility of an Online Mindfulness-Based Intervention for Women with Sexual Interest/Arousal Disorder.

Objectives: Difficulties with sexual desire impact up to a third of women and most do not seek or receive appropriate care for these complaints, in part due to stigma, embarrassment, and limited availability of treatment. In-person mindfulness-based interventions have lasting benefits to sexual desire and sex-related distress in controlled clinical trials but are difficult to access. Online cognitive-behavioral interventions for sexual concerns have shown promising findings, but online mindfulness interventions have received little testing. The current study assessed the feasibility of an online program (called eSense-Mindfulness) adapted from an effective face-to-face intervention for women with Sexual Interest/Arousal Disorder. Methods: Thirty cisgender women (M age = 35.3) with Sexual Interest/Arousal Disorder consented and completed at least one of the eight modules of eSense-Mindfulness while providing weekly feedback regarding their experience. Feasibility was assessed via attrition rates and participant self-report regarding challenges of using the program. Limited efficacy testing was based on effect sizes for changes in sexual response and sex-related distress. Results: Participants (n = 25 who completed all testing) reported high levels of usability and ease of understanding content and reported the mindfulness exercises as well as the information on partner communication to be the most relevant. Limited efficacy testing showed large effect sizes for reductions in sex-related distress, and improvements in sexual desire, arousal, and satisfaction whereas there were smaller effect sizes for improvements in lubrication, orgasm, and vaginal pain. Conclusions: The findings suggest that efficacious face-to-face mindfulness interventions for sexual dysfunction in women show excellent evidence of feasibility when delivered online without personalized guidance.