Molecular and cellular mechanisms of teneurin signaling in synaptic partner matching.

In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionarily conserved teneurins are transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurins' functions is unclear. Here, we use in situ proximity labeling to obtain the intracellular interactome of a teneurin (Ten-m) in the Drosophila brain. Genetic interaction studies using quantitative partner matching assays in both olfactory receptor neurons (ORNs) and projection neurons (PNs) reveal a common pathway: Ten-m binds to and negatively regulates a RhoGAP, thus activating the Rac1 small GTPases to promote synaptic partner matching. Developmental analyses with single-axon resolution identify the cellular mechanism of synaptic partner matching: Ten-m signaling promotes local F-actin levels and stabilizes ORN axon branches that contact partner PN dendrites. Combining spatial proteomics and high-resolution phenotypic analyses, this study advanced our understanding of both cellular and molecular mechanisms of synaptic partner matching.

Programmed Secretion Arrest and Receptor-Triggered Toxin Export during Antibacterial Contact-Dependent Growth Inhibition.

Contact-dependent growth inhibition (CDI) entails receptor-mediated delivery of CdiA-derived toxins into Gram-negative target bacteria. Using electron cryotomography, we show that each CdiA effector protein forms a filament extending ∼33 nm from the cell surface. Remarkably, the extracellular filament represents only the N-terminal half of the effector. A programmed secretion arrest sequesters the C-terminal half of CdiA, including the toxin domain, in the periplasm prior to target-cell recognition. Upon binding receptor, CdiA secretion resumes, and the periplasmic FHA-2 domain is transferred to the target-cell outer membrane. The C-terminal toxin region of CdiA then penetrates into the target-cell periplasm, where it is cleaved for subsequent translocation into the cytoplasm. Our findings suggest that the FHA-2 domain assembles into a transmembrane conduit for toxin transport into the periplasm of target bacteria. We propose that receptor-triggered secretion ensures that FHA-2 export is closely coordinated with integration into the target-cell outer membrane. VIDEO ABSTRACT.

Structural basis of microRNA biogenesis by Dicer-1 and its partner protein Loqs-PB.

In animals and plants, Dicer enzymes collaborate with double-stranded RNA-binding domain (dsRBD) proteins to convert precursor-microRNAs (pre-miRNAs) into miRNA duplexes. We report six cryo-EM structures of Drosophila Dicer-1 that show how Dicer-1 and its partner Loqs­PB cooperate (1) before binding pre-miRNA, (2) after binding and in a catalytically competent state, (3) after nicking one arm of the pre-miRNA, and (4) following complete dicing and initial product release. Our reconstructions suggest that pre-miRNA binds a rare, open conformation of the Dicer­1⋅Loqs­PB heterodimer. The Dicer-1 dsRBD and three Loqs­PB dsRBDs form a tight belt around the pre-miRNA, distorting the RNA helix to place the scissile phosphodiester bonds in the RNase III active sites. Pre-miRNA cleavage shifts the dsRBDs and partially closes Dicer-1, which may promote product release. Our data suggest a model for how the Dicer­1⋅Loqs­PB complex affects a complete cycle of pre-miRNA recognition, stepwise endonuclease cleavage, and product release.

The RsfSR two-component system regulates SigF function by monitoring the state of the respiratory electron transport chain in Mycobacterium smegmatis.

In Mycobacterium smegmatis, the transcriptional activity of the alternative sigma factor SigF is posttranslationally regulated by the partner switching system consisting of SigF, the anti-SigF RsbW1, and three anti-SigF antagonists (RsfA, RsfB, and RsbW3). We previously demonstrated that expression of the SigF regulon is strongly induced in the Δaa3 mutant of M. smegmatis lacking the aa3 cytochrome c oxidase, the major terminal oxidase in the respiratory electron transport chain. Here, we identified and characterized the RsfSR two-component system involved in regulating the phosphorylation state of the major anti-SigF antagonist RsfB. RsfS (MSMEG_6130) is a histidine kinase with the cyclase/histidine kinase-associated sensing extracellular 3 domain at its N terminus, and RsfR (MSMEG_6131) is a receiver domain-containing protein phosphatase 2C-type phosphatase that can dephosphorylate phosphorylated RsfB. We demonstrated that phosphorylation of RsfR on Asp74 by RsfS reduces the phosphatase activity of RsfR toward phosphorylated RsfB and that the cellular abundance of the active unphosphorylated RsfB is increased in the Δaa3 mutant relative to the WT strain. We also demonstrated that the RsfSR two-component system is required for induction of the SigF regulon under respiration-inhibitory conditions such as inactivation of the cytochrome bcc1 complex and aa3 cytochrome c oxidase, as well as hypoxia, electron donor-limiting, high ionic strength, and low pH conditions. Collectively, our results reveal a key regulatory element involved in regulating the SigF signaling system by monitoring the state of the respiratory electron transport chain.

Screening membraneless organelle participants with machine-learning models that integrate multimodal features.

Protein self-assembly is one of the formation mechanisms of biomolecular condensates. However, most phase-separating systems (PS) demand multiple partners in biological conditions. In this study, we divided PS proteins into two groups according to the mechanism by which they undergo PS: PS-Self proteins can self-assemble spontaneously to form droplets, while PS-Part proteins interact with partners to undergo PS. Analysis of the amino acid composition revealed differences in the sequence pattern between the two protein groups. Existing PS predictors, when evaluated on two test protein sets, preferentially predicted self-assembling proteins. Thus, a comprehensive predictor is required. Herein, we propose that properties other than sequence composition can provide crucial information in screening PS proteins. By incorporating phosphorylation frequencies and immunofluorescence image-based droplet-forming propensity with other PS-related features, we built two independent machine-learning models to separately predict the two protein categories. Results of independent testing suggested the superiority of integrating multimodal features. We performed experimental verification on the top-scored proteins DHX9, Ki-67, and NIFK. Their PS behavior in vitro revealed the effectiveness of our models in PS prediction. Further validation on the proteome of membraneless organelles confirmed the ability of our models to identify PS-Part proteins. We implemented a web server named PhaSePred (http://predict.phasep.pro/) that incorporates our two models together with representative PS predictors. PhaSePred displays proteome-level quantiles of different features, thus profiling PS propensity and providing crucial information for identification of candidate proteins.

Religious leaders can motivate men to cede power and reduce intimate partner violence: Experimental evidence from Uganda.

Violence committed by men against women in intimate relationships is a pervasive problem around the world. Patriarchal norms that place men as the head of household are often to blame. Previous research suggests that trusted authorities can shift perceptions of norms and create behavior change. In many settings, a compelling authority on behavior in relationships is religious leaders, who are influential sources of information about proper conduct in relationships and gatekeepers of marriage, but may also uphold traditional gender roles. One way leaders exert their influence is through premarital or couples counseling courses. In this study, we test whether, if given an opportunity to offer a more progressive religious interpretation of gender roles during these courses, religious leaders could motivate men to share power and thereby reduce violence. Building on existing faith networks of Christian religious leaders in western Uganda, we conducted a large pair-matched, randomized controlled trial among 1,680 heterosexual couples in which participants were randomized to attend a 12-session group counseling course or wait-listed. We find that the program shifted power from men to women and reduced intimate partner violence by five percentage points, comparable with more intensive secular programs. These improvements were largest among couples counseled by religious leaders who held the most progressive views at baseline and who critically engaged with the material. Our findings suggest that religious leaders can be effective agents of change for reducing violence.

CDC-Funded HIV Testing Services Outcomes in Ending the HIV Epidemic in the U.S. (EHE) and Non-EHE Jurisdictions, 2021.

BACKGROUND: Ending the HIV Epidemic in the U.S. (EHE) aims to end the HIV epidemic by focusing on 57 jurisdictions most impacted by HIV. METHODS: Using 2021 data from the National HIV Prevention Program Monitoring and Evaluation system, we calculated distributions of CDC-funded HIV tests and HIV testing services outcomes in EHE and non-EHE jurisdictions. We conducted chi-square tests and robust Poisson regression to compare differences in outcomes. RESULTS: Of the 1,753,873 tests conducted, a greater proportion were conducted in EHE (65.7%) versus non-EHE (34.3%) jurisdictions (p<0.001). Greater number of persons newly diagnosed were identified in EHE (n=5,861) versus non-EHE (n=2,329) jurisdictions; newly diagnosed positivity was higher in EHE (0.5%) versus non-EHE (0.4%; PR=1.31, 95% CI: 1.25-1.38) jurisdictions. Among persons newly diagnosed, there were no differences in proportion of linkage to care within 30 days in EHE jurisdictions (77.9%) versus non-EHE jurisdictions (77.1%; PR=1.01, 95% CI: 0.95-1.07). Proportion of persons newly diagnosed interviewed for partner services was lower in EHE (69.0%) versus non-EHE (84.8%; PR=0.81, 95% CI: 0.76-0.87) jurisdictions. CONCLUSION: CDC-funded HIV testing services in EHE jurisdictions conducted more HIV testing and diagnosed more persons. Jurisdictions can further expand HIV testing and related services to continue striving toward EHE goals.

Allosteric modulation of cytochrome P450 enzymes by the NADPH cytochrome P450 reductase FMN-containing domain.

NADPH-cytochrome P450 reductase delivers electrons required by heme oxygenase, squalene monooxygenase, fatty acid desaturase, and 48 human cytochrome P450 enzymes. While conformational changes supporting reductase intramolecular electron transfer are well defined, intermolecular interactions with these targets are poorly understood, in part because of their transient association. Herein the reductase FMN domain responsible for interacting with targets was fused to the N-terminus of three drug-metabolizing and two steroidogenic cytochrome P450 enzymes to increase the probability of interaction. These artificial fusion enzymes were profiled for their ability to bind their respective substrates and inhibitors and to perform catalysis supported by cumene hydroperoxide. Comparisons with the isolated P450 enzymes revealed that even the oxidized FMN domain causes substantial and diverse effects on P450 function. The FMN domain could increase, decrease, or not affect total ligand binding and/or dissociation constants depending on both P450 enzyme and ligand. As examples, FMN domain fusion has no effect on inhibitor ketoconazole binding to CYP17A1 but substantially altered CYP21A2 binding of the same compound. FMN domain fusion to CYP21A2 resulted in differential effects dependent on whether the ligand was 17α-hydroxyprogesterone versus ketoconazole. Similar enzyme-specific effects were observed on steady-state kinetics. These observations are most consistent with FMN domain interacting with the proximal P450 surface to allosterically impact P450 ligand binding and metabolism separate from electron delivery. The variety of effects on different P450 enzymes and on the same P450 with different ligands suggests intricate and differential allosteric communication between the P450 active site and its proximal reductase-binding surface.

Patients with ASPSCR1-TFE3 fusion achieve better response to ICI based combination therapy among TFE3-rearranged renal cell carcinoma.

BACKGROUND: TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare but highly heterogeneous renal cell carcinoma (RCC) entity, of which the clinical treatment landscape is largely undefined. This study aims to evaluate and compare the efficacy of different systemic treatments and further explore the molecular correlates. METHODS: Thirty-eight patients with metastatic TFE3-rRCC were enrolled. Main outcomes included progression-free survival (PFS), overall survival, objective response rate (ORR) and disease control rate. RNA sequencing was performed on 32 tumors. RESULTS: Patients receiving first-line immune checkpoint inhibitor (ICI) based combination therapy achieved longer PFS than those treated without ICI (median PFS: 11.5 vs. 5.1 months, P = 0.098). After stratification of fusion partners, the superior efficacy of first-line ICI based combination therapy was predominantly observed in ASPSCR1-TFE3 rRCC (median PFS: not reached vs. 6.5 months, P = 0.01; ORR: 67.5% vs. 10.0%, P = 0.019), but almost not in non-ASPSCR1-TFE3 rRCC. Transcriptomic data revealed enrichment of ECM and collagen-related signaling in ASPSCR1-TFE3 rRCC, which might interfere with the potential efficacy of anti-angiogenic monotherapy. Whereas angiogenesis and immune activities were exclusively enriched in ASPSCR1-TFE3 rRCC and promised the better clinical outcomes with ICI plus tyrosine kinase inhibitor combination therapy. CONCLUSIONS: The current study represents the largest cohort comparing treatment outcomes and investigating molecular correlates of metastatic TFE3-rRCC based on fusion partner stratification. ICI based combination therapy could serve as an effective first-line treatment option for metastatic ASPSCR1-TFE3 rRCC patients. Regarding with other fusion subtypes, further investigations should be performed to explore the molecular mechanisms to propose pointed therapeutic strategy accordingly.

Climate and Gender: Association Between Droughts and Intimate Partner Violence in India.

Extreme climate events are related to women's exposure to different forms of violence. We examined the relationship between droughts and physical, sexual, and emotional intimate partner violence (IPV) in India by using 2 different definitions of drought: precipitation-based drought and socioeconomic drought. We analyzed data from 2 rounds of a nationally representative survey, the National Family Health Survey, where married women were asked about their experiences of IPV in the previous year (2015-2016 and 2019-2021; n = 122,696). Precipitation-based drought was estimated using remote sensing data and geographic information system (GIS) mapping, while socioeconomic drought status was collected from government records. Logistic regression models showed precipitation-based drought to increase the risk of experiencing physical IPV and emotional IPV. Similar findings were observed for socioeconomic drought; women residing in areas classified as drought-impacted by the government were more likely to report physical IPV, sexual IPV, and emotional IPV. These findings support the growing body of evidence regarding the relationship between climate change and women's vulnerability, and highlight the need for gender responsive strategies for disaster management and preparedness.

Mediating effects of inequitable gender norms on intimate partner violence and contraceptive use in a cluster randomized control trial in Niger.

Previous research has demonstrated that the Reaching Married Adolescents intervention (RMA) was associated with changes in inequitable gender norms, intimate partner violence (IPV), and modern contraceptive use. This study seeks to understand if changes in inequitable gender norms mediate the RMA intervention's effects on contraceptive use and intimate partner violence (IPV). A four-arm cluster randomized control trial was conducted to evaluate effects of the RMA intervention (household visits, small groups, combination, control) on married adolescent girls and their husbands in Dosso, Niger (baseline: 1042 dyads; 24m follow-up: 737 dyads; 2016-2019). Mediation was assessed using inverse odds ratio weighting. In the small group intervention, of the total effect on IPV prevalence (8% reduction), indirect effects via inequitable gender norms is associated with a 2% decrease (95% CI: -0.07, 0.12) and direct effects with a 6% decrease (95% CI: -0.20, -0.02). For household visits, of the total effect on contraceptive use (20% increase), the indirect effect accounts for an 11% decrease (95% CI: -0.18, -0.01) and direct effect, a 32% increase (95% CI: 0.13, 0.44); similar to findings for the combination arm. This experimental evidence informs the value of changing underlying social norms to reduce IPV and increase contraception use.

Personality heterophily and friendship as drivers for successful cooperation.

Cooperation is widespread and arguably a pivotal evolutionary force in maintaining animal societies. Yet, proximately, what underlying motivators drive individuals to cooperate remains relatively unclear. Since 'free-riders' can exploit the benefits by cheating, selecting the right partner is paramount. Such decision rules need not be based on complex calculations and can be driven by cognitively less-demanding mechanisms, like social relationships (e.g. kinship, non-kin friendships, dyadic tolerance), social status (e.g. dominance hierarchies) and personalities (social and non-social traits); however, holistic evidence related to those mechanisms is scarce. Using the classical 'loose-string paradigm', we tested cooperative tendencies of a hierarchical primate, the long-tailed macaque (Macaca fascicularis). We studied three groups (n = 21) in their social settings, allowing partner choice. We supplemented cooperation with observational and experimental data on social relationships, dominance hierarchies and personality. Friendship and dissimilarities in non-social 'exploration' and 'activity-sociability' personality traits predicted the likelihood of cooperative dyad formation. Furthermore, the magnitude of cooperative success was positively associated with friendship, low rank-distance and dissimilarity in the activity-sociability trait. Kinship did not affect cooperation. While some findings align with prior studies, the evidence of (non-social) personality heterophily promoting cooperation may deepen our understanding of the proximate mechanisms and, broadly, the evolution of cooperation.

Violence Against Women as a Global Public Health Issue.

Violence against women, especially intimate partner violence, is recognized as a global public health issue due to its prevalence and global reach. This article outlines the scope of the issue, with respect to its prevalence, health outcomes, and risk factors, and identifies key milestones that led to its global recognition: methodological and data advances, acknowledgment as a criminal justice and health issue, support by the global women's movement, and the robust evidence demonstrating that intimate partner violence is preventable. Key issues for the future include recognition and consideration of intersectionality in research, improvements in the measurement of other forms of violence against women, and the need to scale up prevention efforts that have documented success. Violence against women is an urgent priority as it affects individuals, their families and surroundings, and the entire global health community.

Livebirth rates are influenced by an interaction between male and female partners' age: analysis of 59 951 fresh IVF/ICSI cycles with and without male infertility.

STUDY QUESTION: Does advanced male partner's age impact live birth rates (LBRs) in IVF treatment when female partner's age is factored in? SUMMARY ANSWER: In fresh IVF cycles LBRs decline with male partner's age ≥40 years when the female partner is aged 35-39 years, irrespective of the presence or absence of male factor; but not when the female partner is <35 years or ≥40 years of age; this decline is not observed in ICSI cycles. WHAT IS KNOWN ALREADY: Advanced paternal age is associated with declining sperm parameters, impaired embryo development, compromised pregnancy outcomes, and abnormalities in the offspring in IVF/ICSI cycles. However, data on the interaction between maternal and paternal age on IVF outcomes are very limited and inconsistent. No significant effect of male partner's age on pregnancy outcomes has been noted in donor oocyte cycles. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of all eligible autologous IVF/ICSI cycles with oocyte retrieval and intended fresh embryo transfer (ET) from the UK's national anonymized registry, published online by the Human Fertilisation and Embryology Authority (HFEA). There were 59 951 cycles that qualified the inclusion criteria in the study period: 1 January 2017 to 31 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples underwent IVF (n = 27 226) or ICSI (n = 32 725) treatment with partner's sperm followed by fresh ET due to unexplained (n = 31 846), tubal (n = 6605), or male infertility (n = 22 905). Treatment cycles with endometriosis (n = 5563), ovulatory disorders (n = 9970), female partner aged >44 years (n = 636), and PGT (n = 280) were excluded. Women were stratified by age in the following groups: <35, 35-39, 40-42, and 43-44 years; male partner's age as <35 (reference group), 35-37, 38-39, 40-42, 43-44, 45-50, 51-55, 55-60, and >55 years as presented by the HFEA. Some age-groups were merged in the analysis to increase the population size. Chi-square test was used to compare binominal data; and multiple logistic regression to find any association between male and female age-groups on live birth adjusting for other confounders that had a significant effect on this outcome. MAIN RESULTS AND THE ROLE OF CHANCE: LBRs per oocyte retrieval as well as per ET were no different across the male partners' age-groups when the female partners were aged <35 years or in 40- to 44-year age-group, whether male-factor infertility was included or excluded and whether it was IVF or ICSI cycle. However, when IVF was the method of insemination in the female partner's age-group of 35-39 years, LBRs per oocyte retrieval dropped significantly from 27.0% in the male age-group of <35 years (reference group) to 22.9% (P = 0.002), 22.0% (P = 0.006), and 18.8% (P = 0.004) in 40-44, 45-50, and >50 years age-group, respectively in population that included male-factor infertility. Likewise, LBR per retrieval declined from 27.6% in 35 years age-group to 23.5% (P = 0.002) and 22.2% (P = 002) in 40-44 years and older groups, respectively in cycles without male infertility. However, there was no impact of male age on LBR in any female partner's age-group when ICSI was performed in either the presence or the absence of male infertility. A similar decline in the LBR per retrieval and per ET was observed in female age-group of 35-39 years in the analyses with IVF and ICSI cycles combined. The inference remained unchanged when only the first treatment cycle was included (per patient analysis) or when single blastocyst transfer cycles were analysed, eliminating the impact of the number and stage of embryo transferred. After adjusting for confounders including male age, female age, number of previous treatment cycles, previous live birth, insemination method (IVF or ICSI), number of embryos transferred, and day (stage) of ET, male partner's age remained significantly associated with LBR in the female age-group of 35-39 years, but not when women were in <35 years or 40- to 44-year age-group, in population including as well as excluding male infertility. Miscarriage rates per single ET trended to rise (non-significantly) in IVF as well as ICSI cycle only when men were over 55 years and female partners aged <40 years, particularly when male infertility was excluded. LIMITATIONS, REASONS FOR CAUTION: Information on ovarian reserve and stimulation protocols was not available. This probably would have had little impact, given the large size of the population studied. The ages of female and male partners were given in groups necessitating taking them as ordinal variable in the regression analysis. Cumulative LBRs could not be determined as the information on subsequent frozen-thawed ET cycles could not be traced and the severity or cause of abnormal semen parameters were not present in the HFEA database. Some age-groups with small number of patients were merged to obtain a reliable result. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest clinical data to support the laboratory evidence of the ability of oocytes from young women to reverse the age-related deterioration of sperm quality. As the ageing oocytes lose this reparatory mechanism, the ageing sperm exert a detrimental effect on the LBR. The message of this study is important in counselling of patients and planning out treatment. Further research on interaction between male and female age will increase our understanding of this matter and help to establish whether ICSI procedure is more appropriate for older male partners even when there is no apparent semen abnormality. STUDY FUNDING/COMPETING INTEREST(S): No funding was required. There is no competing interest. TRIAL REGISTRATION NUMBER: N/A (retrospective analysis).

Implementation preferences for the management of sexually transmitted infections in the South African health system: a discrete choice experiment.

OBJECTIVES: Despite strengthening HIV prevention with the introduction of pre-exposure prophylaxis (PrEP), STI services have remained relatively unchanged and the standard of care remains syndromic management. We used a discrete choice experiment to investigate service users' preferences for the diagnosis and treatment of STIs in South Africa. METHODS: Between 1 March 2021 and 20 April 2021, a cross-sectional online questionnaire hosted on REDCap was administered through access links sent to WhatsApp support groups for HIV PrEP users and attendees of two primary healthcare clinics and two mobile facilities in the Eastern Cape and Gauteng provinces aged between 18 and 49 years. Participants either self-completed the questionnaire or received support from a research assistant. We used a conditional logit model for the initial analysis and latent class model (LCM) to establish class memberships, with results displayed as ORs and probabilities. RESULTS: We enrolled 496 individuals; the majority were female (69%) and <30 years (74%). The LCM showed two distinct groups. The first group, comprising 68% of the participants, showed a strong preference for self-sampling compared with no sampling (OR 2.16, 95% CI 1.62 to 2.88). A clinic follow-up appointment for treatment was less preferable to same-day treatment (OR 0.78, 95% CI 0.63 to 0.95). Contact slip from index patient (OR 0.86, 95% CI 0.76 to 0.96) and healthcare professional (HCP)-initiated partner notification (OR 0.63, 95% CI 0.55 to 0.73) were both less preferable than expedited partner treatment (EPT). The second group included 32% of participants with a lower preference for self-sampling compared with no sampling (OR 0.65, 95% CI 0.41 to 1.04). There was no treatment option that was significantly different from the others; however, there was a strong preference for HCP-initiated partner notification to EPT (OR 1.53, 95% CI 1.10 to 2.12). CONCLUSIONS: Our results suggest that service users preferred STI testing prior to treatment, with the majority preferring self-taken samples and receiving aetiology-based treatment on the same day.

The effectiveness of couple-based interventions on the marital outcomes of women with genital and breast cancer and their partners: a systematic review and meta-analysis.

BACKGROUND: Breast cancer and genital cancer are known as cancers that affect people's relationships with their partners. Women with such cancers are emotionally vulnerable and need more support from their partners. The present systematic review and meta-analysis evaluated the effectiveness of couple-based interventions on the marital outcomes of patients with these cancers and their intimate partners. METHODS: To perform this systematic review, Google Scholar and databases such as PubMed, Web of Science, Cochrane, Scopus, SID (Scientific Information Database), and Magiran were searched systematically. The reviewed studies included randomized controlled trials and quasiexperimental studies in which the intervention group, couple-based interventions, and the control group received routine care, general education or no intervention for cancer treatment. In this study, the included participants were patients with breast cancer or genital cancer and their intimate partners. The primary outcomes considered in this study included patients' marital adjustment, patients' marital satisfaction, patients' marital intimacy, and patients' marital relationships. The secondary outcomes were partners' marital adjustment, partners' marital satisfaction, partners' marital intimacy, and partners' marital relationships. A meta-analysis was performed with Review Manager v. 5.3 software (The Nordic Cochrane Centre, Cochrane Collaboration, 2014; Copenhagen, Denmark). The intervention impacts on continuous outcomes were measured using standardized mean differences (SMDs) with 95% confidence interval because of the use of various scales to evaluate the outcomes. The quality of evidence presented in the included studies was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. In the subgroup analysis, the studied outcomes were divided into two parts (theory-based and non-theory-based) in terms of the theoretical context of couple-based interventions. RESULTS: From a total of 138 retrieved studies, 14 trials were eligible for inclusion in the study. The results of the meta-analysis showed that the patient's marital satisfaction increased significantly with couple-based interventions (SMD 0.46, 95% confidence interval 0.07 to 0.85; 7 trials, 341 patients, very low certainty) compared to the control group, but the evidence was uncertain. However, there were no significant differences between the groups in the partner's marital satisfaction, the patient's and partner's marital adjustment, and the patient's and partner's marital intimacy. Additionally, the results of the subgroup analysis showed that the couple-based interventions significantly increased the patient's marital adjustment (SMD 1.96, 95% CI 0.87 to 3.06; 4 trials, 355 patients, very low certainty), the partner's marital adjustment (SMD 0.53, 95% CI 0.20 to 0.86; 4 trials, 347 partners, very low certainty), the patient's marital satisfaction (SMD 0.89, 95% CI 0.35 to 1.43; 2 trials, 123 patients, very low certainty), and the partner's marital satisfaction (SMD 0.57, 95% CI 0.20 to 0.94; 2 trials, 123 partners, very low certainty) compared to the control group in theory-based studies. In. However, in non-theory-based studies, the results of the meta-analysis revealed no significant differences between the intervention and control groups. CONCLUSIONS: The results of this study demonstrated the impact of couple-based interventions on the marital outcomes of patients with breast and genital cancers. Because of the very low confidence in the evidence, high-quality randomized trials with a sufficient sample size should be conducted considering the proper theoretical context.

A tale of two marital stressors: Comparing proinflammatory responses to partner distress and marital conflict.

Marital quality shares ties to inflammatory conditions like cardiovascular disease and diabetes. For decades, research has focused on marital conflict as a primary mechanism given its potential to trigger inflammatory responses. However, longitudinal evidence suggests that marital conflict declines over time, and little attention has been paid to the inflammatory aftermath of other types of marital exchanges. A spouse's emotional distress is an important but overlooked marital context, as partners are exposed to each other's upsetting emotions throughout adulthood. To directly compare reactivity in proinflammatory gene expression to these two marital stressors and to examine differences by age and marital satisfaction, 203 community adults ages 25-90 (N = 102 couples) provided blood samples and rated their negative mood before and after they 1) watched their partner relive an upsetting personal memory and, in a separate visit 1-2 weeks later, 2) discussed a conflictual topic in their relationship. Controlling for age, sex, race/ethnicity, BMI, alcohol use, smoking, and comorbidities, increases in proinflammatory gene expression were significantly larger after the partner's upsetting disclosure than after marital conflict (B = 0.073, SE = 0.031, p = .018). This pattern paralleled emotional reactivity to the tasks, wherein negative mood rose more in response to the partner's disclosure than to marital conflict (B = 4.305, SE = 1.468, p = .004). In sum, proinflammatory and mood reactivity to spousal distress exceeded reactivity to marital conflict, a well-established marital stressor. Findings reveal spousal distress as a novel mechanism that may link marriage to inflammation-related diseases, and even pose risks for both happy and unhappy couples across adulthood.

How to Involve Patients in GRAPPA Research as Partners.

Patient research partners (PRPs) have been actively participating in the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meetings, working groups, and research activities since 2013. As they have evolved, the PRPs operate as a cohesive group supported by their GRAPPA-approved handbook and policy documents. The number of involved PRPs has increased, allowing more opportunity for the incorporation of the patient voice and experience in GRAPPA activities. In the GRAPPA proceedings, PRPs regularly report on their involvement in the meetings and research projects. During a 30-minute plenary session at the GRAPPA 2023 annual meeting, attendees were informed about the evolving roles of PRPs in GRAPPA and beyond and were asked to provide feedback on their experience and opinions regarding PRP involvement in psoriatic disease research. Here we report the key messages of the session, including polling results, examples of PRP involvement, and ongoing challenges.

Modeling US blood donor deferrals under a policy of individual risk assessment for HIV risk sexual behavior.

BACKGROUND: In May 2023, the Food and Drug Administration (FDA) released final guidance for blood donor eligibility that recommended the elimination of 3-month deferral for men who have sex with men (MSM) and the related deferral for women who have sex with MSM. In its place, FDA introduced an individual risk assessment policy of asking all presenting blood donors, regardless of sex or gender, if they have had a new partner or more than one sexual partner in the last 3 months and deferring those who also report anal sex (penile-anal intercourse) during this period. We modeled the possible impact of this policy on the US blood donor base. STUDY DESIGN AND METHODS: We developed a computational model to estimate the percentage of blood donors who would be deferred under a policy of individual HIV risk assessment. The model incorporated demographic information about donors and national survey data on HIV risk behaviors and included age and sex distributions and dependencies. RESULTS: Our model estimates that approximately 1.2% of US blood donors would be deferred under the individual HIV risk assessment paradigm. DISCUSSION: The model predicts a relatively minor effect of replacing the time-based deferral for MSM with individual risk-based deferral for sexual behavior. As US blood centers implement this new policy, the effect may be mitigated by donor gains, which warrant further study. The new policy is unlikely to adversely affect the availability of blood and blood components.

Longitudinal changes in sexual desire and attraction among women who started using the Natural Cycles app.

Many women experience sexual side effects, such as decreased libido, when taking hormonal contraceptives (HCs). However, little is known about the extent to which libido recovers after discontinuing HCs, nor about the timeframe in which recovery is expected to occur. Given that HCs suppress the activities of multiple endogenous hormones that regulate both the ovulatory cycle and women's sexual function, resumption of cycles should predict libido recovery. Here, using a combination of repeated and retrospective measures, we examined changes in sexual desire and partner attraction (among partnered women) across a three-month period in a sample of Natural Cycles users (Survey 1: n = 1596; Survey 2: n = 550) who recently discontinued HCs. We also tested whether changes in these outcomes coincided with resumption of the ovulatory cycle and whether they were associated with additional factors related to HC use (e.g., duration of HC use) or relationship characteristics (e.g., relationship length). Results revealed that both sexual desire and partner attraction, on average, increased across three months after beginning to use Natural Cycles. While the prediction that changes in sexual desire would co-occur with cycle resumption was supported, there was also evidence that libido continued to increase even after cycles resumed. Together, these results offer new insights into relationships between HC discontinuation and women's sexual psychology and lay the groundwork for future research exploring the mechanisms underlying these effects.