High life satisfaction reported among small-scale societies with low incomes.

Global polls have shown that people in high-income countries generally report being more satisfied with their lives than people in low-income countries. The persistence of this correlation, and its similarity to correlations between income and life satisfaction within countries, could lead to the impression that high levels of life satisfaction can only be achieved in wealthy societies. However, global polls have typically overlooked small-scale, nonindustrialized societies, which can provide an alternative test of the consistency of this relationship. Here, we present results from a survey of 2,966 members of Indigenous Peoples and local communities among 19 globally distributed sites. We find that high average levels of life satisfaction, comparable to those of wealthy countries, are reported for numerous populations that have very low monetary incomes. Our results are consistent with the notion that human societies can support very satisfying lives for their members without necessarily requiring high degrees of monetary wealth.

A quantitative framework for identifying the role of individual species in Nature's Contributions to People.

It is widely acknowledged that biodiversity change is affecting human well-being by altering the supply of Nature's Contributions to People (NCP). Nevertheless, the role of individual species in this relationship remains obscure. In this article, we present a framework that combines the cascade model from ecosystem services research with network theory from community ecology. This allows us to quantitatively link NCP demanded by people to the networks of interacting species that underpin them. We show that this "network cascade" framework can reveal the number, identity and importance of the individual species that drive NCP and of the environmental conditions that support them. This information is highly valuable in demonstrating the importance of biodiversity in supporting human well-being and can help inform the management of biodiversity in social-ecological systems.

Pathologist workload, burnout, and wellness: connecting the dots.

No standard tool to measure pathologist workload currently exists. An accurate measure of workload is needed for determining the number of pathologists to be hired, distributing the workload fairly among pathologists, and assessing the overall cost of pathology consults. Initially, simple tools such as counting cases or slides were used to give an estimate of the workload. More recently, multiple workload models, including relative value units (RVUs), the Royal College of Pathologists (RCP) point system, Level 4 Equivalent (L4E), Work2Quality (W2Q), and the University of Washington, Seattle (UW) slide count method, have been developed. There is no "ideal" model that is universally accepted. The main differences among the models come from the weights assigned to different specimen types, differential calculations for organs, and the capture of additional tasks needed for safe and timely patient care. Academic centers tend to see more complex cases that require extensive sampling and additional testing, while community-based and private laboratories deal more with biopsies. Additionally, some systems do not account for teaching, participation in multidisciplinary rounds, quality assurance activities, and medical oversight. A successful workload model needs to be continually updated to reflect the current state of practice.Awareness about physician burnout has gained attention in recent years and has been added to the World Health Organization's International Classification of Diseases (World Health Organization, WHO) as an occupational phenomenon. However, the extent to which this affects pathologists is not well understood. According to the WHO, burnout syndrome is diagnosed by the presence of three components: emotional exhaustion, depersonalization from one's work (cynicism related to one's job), and a low sense of personal achievement or accomplishment. Three drivers of burnout are the demand for productivity, lack of recognition, and electronic health records. Prominent consequences of physician burnout are economic and personal costs to the public and to the providers.Wellness is physical and mental well-being that allows individuals to manage stress effectively and to thrive in both their professional and personal lives. To achieve wellness, it is necessary to understand the root causes of burnout, including over-work and working under stressful conditions. Wellness is more than the absence of stress or burnout, and the responsibility of wellness should be shared by pathologists themselves, their healthcare organization, and governing bodies. Each pathologist needs to take their own path to achieve wellness.

Venkatapuram Responds to "Positive epidemiology, revisited: The case for centering human rights and economic justice".

This commentary responds to the article by Qureishi et al. (Am J Epidemol. XXXX;XXX(XX):XXXX-XXXX)) that criticizes a new proposal for "positive epidemiology." They argue that positive epidemiology as it is being proposed and conducted ignores supra-individual social contextual factors that constrain wellbeing of some individuals more than others, and it could exacerbate inequalities if applied at a population level, among other harms. They offer an alternative approach to defining causal factors that are helpful for wellbeing, and seek to ground their view in human rights and economic justice frameworks. This commentary considers their criticisms of PE and suggests that their alternative as well as all research into positive health and wellbeing would benefit from drawing on the ongoing debates and works in health equity and justice philosophy. A coherent conception of health and wellbeing, the link between health/wellbeing and theories of justice, and the capabilities approach are discussed. The efforts at conducting epidemiology for the causes and distribution of good health and wellbeing grounded in justice is welcomed.

Iron deficiency, anemia, and patient-reported outcomes in kidney transplant recipients.

Kidney transplant recipients (KTRs) experience more fatigue, anxiety, and depressive symptoms and lower concentration and health-related quality of life (HRQoL) compared with the general population. Anemia is a potential cause that is well-recognized and treated. Iron deficiency, however, is often unrecognized, despite its potential detrimental effects related to and unrelated to anemia. We investigated the interplay of anemia, iron deficiency, and patient-reported outcomes in 814 outpatient KTRs (62% male, age 56 ± 13 years) enrolled in the TransplantLines Biobank and Cohort Study (Groningen, The Netherlands). In total, 28% had iron deficiency (ie, transferrin saturation < 20% and ferritin < 100 µg/L), and 29% had anemia (World Health Organization criteria). In linear regression analyses, iron deficiency, but not anemia, was associated with more fatigue, worse concentration, lower wellbeing, more anxiety, more depressive symptoms, and lower HRQoL, independent of age, sex, estimated glomerular filtration rate, anemia, and other potential confounders. In the fully adjusted logistic regression models, iron deficiency was associated with an estimated 53% higher risk of severe fatigue, a 100% higher risk of major depressive symptoms, and a 51% higher chance of being at risk for sick leave/work disability. Clinical trials are needed to investigate the effect of iron deficiency correction on patient-reported outcomes and HRQoL in KTRs.

Communicating the diagnosis of a hematological neoplastic disease to patients' minor children: a multicenter prospective study.

BACKGROUND: When a hematological malignancy is diagnosed, the whole family carries the burden of the disease; parents often try to protect minor children from suffering by avoiding communication about their disease. Since 2009, patients with minors at the Adult Hematology Division at San Gerardo Hospital (Monza) can take part in the "Emanuela Project": children can visit parents and talk with psychologists and hematologists, who explain the disease through simple metaphors. MATERIALS AND METHODS: The EMY STUDY aimed to evaluate the impact of illness-related communication on children's behavior, comparing Monza's experience with other Hematology Units, where the communication is delegated to parents or psychological support. Questionnaires exploring the children's main behaviors (school performance, appetite, sleeping patterns, attachment to family figures, and family dialogue) were administered to both sick (SP) and healthy (HP) parents. From 2017 to 2021, 32 patients were enrolled, 20 from Monza and 12 from other hospitals; 84 questionnaires were globally collected. RESULTS: In Monza's group, no major changes in children's behavior were observed and an open dialogue about the disease was often possible. Disease communication is considered crucial and perceived as a responsibility of parents together with a professional figure, mainly the hematologist. Patients were satisfied with "Emanuela Project," reporting positive effects on doctor-patient relationship. Difficulties in separation were significantly higher at other hospitals (P = .019) than in Monza. While at other centers communication is considered parents' responsibility, Monza's patients emphasize the role of professional figures (P = .007). Differently from other hospitals, the role of the hematologist is crucial to Monza's patients (P = .001). CONCLUSION: Disease communication to patients' offspring is a crucial moment in the process of care, and the hematologist can play a major role in this difficult task, with potential positive effects both on children's well-being and on doctor-patient relationship.

Systemic inflammation and changes in physical well-being in patients with breast cancer: a longitudinal study in community oncology settings.

BACKGROUND: Chemotherapy adversely affects physical well-being and inflammation may be related to changes in physical well-being. We evaluated the association of systemic inflammation with changes in physical well-being. METHODS: In a prospective study of 580 patients with stages I-III breast cancer we assessed immune cell counts, neutrophil:lymphocyte ratio (NLR), lymphocyte:monocyte ratio (LMR), and platelet:lymphocyte ratio (PLR) within 7 days before chemotherapy (pre-chemotherapy). Physical well-being was assessed using the Functional Assessment of Cancer Therapy: General-Physical Well-being subscale (FACT-PWB) pre-chemotherapy and 1 month and 6 months post-chemotherapy. Clinically meaningful decline in physical well-being was determined as decreasing FACT-PWB by more than one point from pre-chemotherapy level, and non-resilience defined as having decline post-chemotherapy and not returning to within one-point of pre-chemotherapy FACT-PWB by 6 months post-chemotherapy. Multivariable logistic regressions examined the association between inflammation and changes in physical well-being, adjusting for sociodemographic and clinical characteristics. RESULTS: Fifty-nine percent (310/529) and 36% (178/501) of participants had physical well-being decline post-chemotherapy and 6 months post-chemotherapy, respectively. Fifty percent (147/294) were non-resilient. Low NLR and PLR were associated with 1.78 (P = .01) and 1.66 (P = .02) fold greater odds of having a decline in physical well-being 6 months post-chemotherapy compared to those with high NLR and PLR, respectively. Low NLR and PLR were associated with 1.92 (P = .02) and 2.09 (P = 0.01) fold greater odds of being non-resilient 6 months post-chemotherapy compared to those with high NLR and PLR, respectively. CONCLUSION: Low NLR and PLR were associated with chemotherapy-induced changes in physical well-being independent of sociodemographic and clinical risk factors.

Characterizing "collateral damage" in men and women with metastatic breast cancer (mBC) from diverse racial and ethnic backgrounds in New York City.

PURPOSE: Patients from diverse racial, ethnic, and socio-economic backgrounds may be particularly vulnerable to experiencing undue social and financial burdens ("collateral damage") from a metastatic breast cancer (mBC) diagnosis; however, these challenges have not been well explored in diverse populations. METHODS: From May 2022 to May 2023, English- or Spanish-speaking adults with mBC treated at four New York-Presbyterian (NYP) sites were invited to complete a survey that assessed collateral damage, social determinants of health, physical and psychosocial well-being, and patient-provider communication. Fisher's exact and the Kruskal-Wallis rank-sum tests assessed differences by race and ethnicity. RESULTS: Of 87 respondents, 14% identified as Hispanic, 28% non-Hispanic Black (NHB), 41% non-Hispanic White (NHW), 7% Asian American Pacific Islander (AAPI), and 10% other/multiracial. While 100% of Hispanic, NHW, and AAPI participants reported stable housing, 29% of NHB participants were worried about losing housing (p = 0.002). Forty-two percent of Hispanic and 46% of NHB participants (vs. 8%, NHW and 0%, AAPI, p = 0.005) were food insecure; 18% of Hispanic and 17% of NHB adults indicated lack of reliable transportation in the last year (vs. 0%, NHW/AAPI, p = 0.033). Participants were generally satisfied with the quality of communication that they had with their healthcare providers and overall physical and mental well-being were modestly poorer relative to healthy population norms. CONCLUSIONS: In our study, NHB and Hispanic mBC patients reported higher levels of financial concern and were more likely to experience food and transportation insecurity compared to NHW patients. Systematically connecting patients with resources to address unmet needs should be prioritized to identify feasible approaches to support economically vulnerable patients following an mBC diagnosis.

Differences in trajectories of quality of life according to type of dementia: 6-year longitudinal findings from the IDEAL programme.

BACKGROUND: People with different types of dementia may have distinct symptoms and experiences that affect their quality of life. This study investigated whether quality of life varied across types of dementia and over time. METHODS: The participants were 1555 people with mild-to-moderate dementia and 1327 carers from the IDEAL longitudinal cohort study, recruited from clinical services. As many as possible were followed for up to 6 years. Diagnoses included were Alzheimer's disease, vascular dementia, mixed Alzheimer's and vascular dementia, Parkinson's disease dementia, dementia with Lewy bodies, and frontotemporal dementia. Self- and informant-rated versions of the Quality of Life in Alzheimer's Disease scale were used. A joint model, incorporating a mixed effects model with random effects and a survival model to account for dropout, was used to examine whether quality of life varied by dementia type at the time of diagnosis and how trajectories changed over time. RESULTS: The strongest associations between dementia type and quality of life were seen around the time of diagnosis. For both self-ratings and informant ratings, people with Parkinson's disease dementia or dementia with Lewy bodies had lower quality of life scores. Over time there was little change in self-rated scores across all dementia types (- 0.15 points per year). Informant-rated scores declined over time (- 1.63 points per year), with the greatest decline seen in ratings by informants for people with dementia with Lewy bodies (- 2.18 points per year). CONCLUSIONS: Self-rated quality of life scores were relatively stable over time whilst informant ratings showed a steeper decline. People with Parkinson's disease dementia or dementia with Lewy bodies report particularly low levels of quality of life, indicating the importance of greater attention to the needs of these groups.

Emotional and functional well-being in long-term breast cancer survivorship.

PURPOSE: Emotional and functional well-being (EWB and FWB) are important components of mental health and quality of life. This study aims to evaluate long-term EWB and FWB in breast cancer (BC) survivors. METHODS: The Carolina Breast Cancer Study Phase 3 oversampled Black and younger (< 50 years in age) women so that they each represent approximately 50% of the study population and assessed participants' EWB and FWB with the Functional Assessment of Cancer Therapy-Breast (FACT-B) at 5- (baseline), 25-, and 84-months post diagnosis. Multinomial logit models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between demographic and clinical characteristics and well-being change relative to baseline. RESULTS: Among 2,781 participants with BC, average EWB and FWB improved with time since diagnosis. Persistent FWB decrements were associated with Black race [OR 1.4 (95% CI 1.2-1.7) and 1.3 (95% CI 1.1-1.6), at 25-months and 84-months respectively], older age [OR 1.4 (95% CI 1.1-1.7) and 1.5 (95% CI 1.2-1.8), respectively], no chemotherapy, and recurrence [OR 2.9 (95% CI 1.8-4.8) and 3.1 (95% CI 2.1-4.6), respectively]. EWB decrements were associated with advanced stage and recurrence. Decrements in combined (FWB+EWB) well-being were associated with recurrence at both follow-up survey timepoints [ORs 4.7 (95% CI 2.7-8.0) and 4.3 (95% CI 2.8-6.6), respectively]. CONCLUSIONS: Long-term well-being varies by demographics and clinical features, with Black women and women with aggressive disease at greatest risk of long-term decrements.

Network analysis to prioritize issues for intervention to improve the health-related quality of life of people with HIV in Spain.

OBJECTIVES: The objective is to assess the interconnectedness of a network of health-related quality of life (HRQoL) variables among people with HIV (PHIV) to identify key areas for which clinical interventions could improve HRQoL for this population. METHODS: Between 2021 and 2023, we carried out a cross-sectional study within the Spanish CoRIS cohort. We conducted a weighted and undirected network analysis, which examines complex patterns of relationships and interconnections between variables, to assess a network of eight HRQoL dimensions from the validated Clinic Screening Tool for HIV (CST-HIV): anticipated stigma, psychological distress, sexuality, social support, material deprivation, sleep and fatigue, cognitive problems and physical symptoms. RESULTS: A total of 347 participants, predominantly male (93.1%), currently working (79.0%), self-reported homosexual (72.6%) and college-educated (53.9%), were included in the study. Psychological distress showed the highest centrality in the network, indicating its strong connections with sleep and fatigue, cognitive problems and social support within the HRQoL network. CONCLUSIONS: Psychological distress, sleep and fatigue, cognitive issues and social support were identified as key factors in an HRQoL network, indicating that interventions focused on these areas could significantly enhance overall well-being.

Reported Intergenerational Transmission of Parent Weight Talk and Links with Child Health and Wellbeing.

OBJECTIVES: To examine if intergenerational transmission of parent weight talk occurs, the contextual factors prompting weight talk, and whether parent weight talk is associated with child weight, dietary intake, psychosocial outcomes, and food parenting practices. STUDY DESIGN: Children aged 5-9 years and their families (n = 1307) from 6 racial and ethnic groups (African-American, Hispanic, Hmong, Native American, Somali/Ethiopian, White) were recruited for a longitudinal cohort study through primary care clinics in Minneapolis/St. Paul, Minnesota from 2016 through 2019. Parents filled out surveys at 2 time points, 18 months apart. Adjusted regression models examined associations of interest. RESULTS: Intergenerational transmission of parent weight talk was observed. In addition, significant associations were found between parent engagement in weight talk and higher weight status and poorer psychosocial outcomes in children 18 months later. Parent engagement in weight talk was also associated with more restrictive food parenting practices 18 months later. CONCLUSIONS: Parents' exposure to weight talk as children increased the likelihood of engaging in weight talk with their own children and had harmful associations over time with parent restrictive feeding practices, child weight, and psychosocial wellbeing in children. Health care providers may want to consider both modeling positive health-focused conversations and educating parents about the potential harmful and long-lasting consequences of engaging in weight talk with their children.

Well-Being Therapy in systemic sclerosis outpatients: a randomized controlled trial.

OBJECTIVES: Systemic Sclerosis (SSc) patients have psychological distress and poor well-being and need a tailored treatment. Psychological interventions, rarely tested for efficacy, showed poor benefits. The present randomized controlled trial tested the efficacy of Well-Being Therapy (WBT) in SSc patients. METHODS: Thirty-two outpatients were randomized (1:1) to WBT (n = 16) or Treatment As Usual (i.e. routine medical check-ups) (TAU) (n = 16). Primary outcome was well-being. Secondary outcomes included functional ability related to SSc, psychological distress, mental pain, suffering. All participants were assessed at baseline (T0). The WBT group was assessed after two months (end of WBT session 4) (T1), after four months (end of WBT session 8) (T2), after seven months (3-month follow-up) (T3), and after 10 months (6-month follow-up) (T4). The TAU group was assessed two (T1), four (T2), seven (T3), and ten (T4) months after baseline. RESULTS: WBT produced a significant improvement in subjective well-being (p ≤ 0.001), personal growth (p = 0.006), self-acceptance (p = 0.003) compared with TAU, maintained at T3 as what concerns subjective well-being (p = 0.012). WBT produced greater decrease in psychological distress (p = 0.010), mental pain (p = 0.010), suffering (p ≤ 0.001) compared with TAU, maintained at T4 as what concerns suffering (p ≤ 0.001). Participants reported high satisfaction with WBT. CONCLUSION: The study provides preliminary evidence on the benefits of WBT as short-term approach for in- and out-patient SSc healthcare paths. Studies with larger samples are needed to have the evidence for recommending WBT to SSc patients.

Fertility clinics have a duty of care towards patients who do not have children with treatment.

In medically assisted reproduction (MAR) success has mostly been measured in terms of achieving (healthy) livebirths. We argue this focus is too narrow and that success should be measured in terms of alleviating patient suffering caused by an unfulfilled child wish. The major implication is that clinics must better tailored care to effectively support patients who do not have child(ren) with treatment. First, we argue that clinics have a duty of care towards patients for whom MAR does not result in children because this is a common treatment outcome, because treatment is burdensome and creates new losses for patients, and because the field has the necessary expertise to provide support and it is part of patient-centred care. Then, we examine concerns about the adequacy of addressing the possibility that treatment may end without children, namely, that this may hinder patients' hope and put them off doing treatment, and that it may be perceived as a sign of clinical incompetence, as well as concerns about the required skill set. We end with a set of research-informed recommendations to promote healthy adjustment to ending fertility treatment without children. These focus on the need to reconceptualize 'success' and 'failure' in MAR, to promote open discussion about the possibility of treatment not resulting in children and encourage patients to develop 'plan(s) B', to support patients who end treatment without children, and to create the organizational structures needed to support clinics and healthcare professionals in this endeavour.

Fertility preservation before cancer treatment: the dilemma of saying 'no' as the price of glory.

A great deal of work has been carried out by professionals in reproductive medicine in order to raise awareness about fertility preservation (FP) techniques, particularly for women, and to ensure that FP is included in the care of young adults treated for cancer or a pathology requiring gonadotoxic treatment. If the importance of the development of our discipline is obvious, our militancy in favour of FP and our emotional projections must not make us forget that medical thinking must be carried out not only on a case-by-case basis, weighing up the benefit-risk balance, but also without losing sight that conceiving a child with one's own gametes is not a vital issue. The cultural importance given to the genetic link with offspring may bias patients' and physicians' decisions, while other ways of achieving parenthood exist, and are often more effective. Systematic information should be provided on the existence of FP techniques, but this should not lead to their systematic implementation, nor should it obscure that early information will also allow patients to begin projecting themselves in alternative options to become parents.

The clinical effectiveness of the Mind/Body Program for Infertility on wellbeing and assisted reproduction outcomes: a randomized controlled trial in search for active ingredients.

STUDY QUESTION: Does the Mind/Body Program for Infertility (MBPI) perform better, due to certain distinctive elements, than a partly matched support group in improving the wellbeing and medically assisted reproduction (MAR) outcomes of women with elevated distress levels in a clinical setting? SUMMARY ANSWER: While robust enhancements occurred in the wellbeing overall, the cognitive behavioural and formalized stress management elements of the MBPI allowed a significantly stronger improvement in trait anxiety, but not in other mental health and MAR outcomes, compared with a support group. WHAT IS KNOWN ALREADY: Mind-body psychological programmes adjacent to MAR have been found to improve women's mental states and possibly increase chances of pregnancy. However, not enough is known about the programme's effectiveness among patients with elevated distress levels in routine clinical settings, nor is it clear which of its particular ingredients are specifically effective. STUDY DESIGN, SIZE, DURATION: A pre-post design, single-centre, randomized controlled trial was performed between December 2019 and October 2022 (start and end of recruitment, respectively). The sample size (n = 168) was calculated to detect superiority of the MBPI in improving fertility-related quality of life. Randomization was computer-based, with random numbers concealing identities of patients until after allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS: The trial was conducted at a large university teaching hospital. A total of 168 patients were randomly assigned to the mind-body (MBPI) group (n = 84) and the fertility support (FS) control group (n = 84). Patients received a 10-week, 135-min/week group intervention, with the FS group following the same format as the MBPI group, but with a less restricted and systematic content, and without the presumed effective factors. The number of patients analysed was n = 74 (MBPI) and n = 68 (FS) for post-intervention psychological outcomes, and n = 54 (MBPI) and n = 56 (FS) for pregnancy outcomes at a 30-month follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: Significant improvements occurred in both groups in all psychological domains (adjusted P < 0.001), except for treatment-related quality of life. Linear mixed-model regression analysis did not reveal significantly greater pre-post improvements in the MBPI group than in the FS group in fertility-related quality of life (difference in differences (DD) = 4.11 [0.42, 7.80], d = 0.32, adjusted P = 0.124), treatment-related quality of life (DD = -3.08 [-7.72, 1.55], d = -0.20, adjusted P = 0.582), infertility-specific stress (DD = -2.54 [-4.68, 0.41], d = -0.36, adjusted P = 0.105), depression (DD = -1.16 [3.61, 1.29], d = -0.13, adjusted P = 0.708), and general stress (DD = -0.62 [-1.91, 0.68], d = -0.13, adjusted P = 0.708), but it did show a significantly larger improvement in trait anxiety (DD = -3.60 [-6.16, -1.04], d = -0.32, adjusted P = 0.042). Logistic regression showed no group effect on MAR pregnancies, spontaneous pregnancies, or live births. LIMITATIONS, REASONS FOR CAUTION: The follow-up only covered MAR-related medical outcomes and no psychological variables, and their rates were not equal in the two groups. Biological factors other than age, aetiology, and duration of infertility may have confounded the study results. Loss to follow-up was between 5% and 10%, which may have led to some bias. WIDER IMPLICATIONS OF THE FINDINGS: The psychologically and medically heterogeneous sample, the normal clinical setting and the low attrition rate all raise the external validity and generalizability of our study. The MBPI works not only in controlled conditions, but also in routine MAR practice, where it can be introduced as a cost-effective, low-intensity psychological intervention, within the framework of stepped care. More studies are needed to further identify its active ingredients. STUDY FUNDING/COMPETING INTEREST(S): The authors received no financial support for the research, authorship, and/or publication of this article. The authors have no conflict of interest to disclose. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04151485. TRIAL REGISTRATION DATE: 5 November 2019. DATE OF FIRST PATIENT'S ENROLMENT: 15 December 2019.

Pirfenidone ameliorates ANIT-induced cholestatic liver injury via modulation of FXR, NF-кB/TNF-α, and Wnt/GSK-3ß/ß-catenin signaling pathways.

Cholestasis is a hepatobiliary disorder characterized by the excessive accumulation of toxic bile acids in hepatocytes, leading to cholestatic liver injury (CLI) through multiple pathogenic inflammatory pathways. Currently, there are limited therapeutic options for the management of cholestasis and associated CLI; therefore, new options are urgently needed. Pirfenidone (PF), an oral bioavailable pyridone analog, is used for the treatment of idiopathic pulmonary fibrosis. PF has recently demonstrated diverse potential therapeutic activities against different pathologies. Accordingly, the present study adopted the α-naphthyl isothiocyanate (ANIT)-induced CLI model in mice to explore the potential protective impact of PF and investigate the underlying mechanisms of action. PF intervention markedly reduced the serum levels of ALT, AST, LDH, total bilirubin, and total bile acids, which was accompanied by a remarkable amelioration of histopathological lesions induced by ANIT. PF also protected the mice against ANIT-induced redox imbalance in the liver, represented by reduced MDA levels and elevated GSH and SOD activities. Mechanistically, PF inhibited ANIT-induced downregulated expressions of the farnesoid X receptor (FXR), as well as the bile salt export pump (BSEP) and the multidrug resistance-associated protein 2 (MRP2) bile acid efflux channels. PF further repressed ANIT-induced NF-κB activation and TNF-α and IL-6 production. These beneficial effects were associated with its ability to dose-dependently inhibit Wnt/GSK-3ß/ß-catenin/cyclin D1 signaling. Collectively, PF protects against ANIT-induced CLI in mice, demonstrating powerful antioxidant and anti-inflammatory activities as well as an ability to oppose BA homeostasis disorder. These protective effects are primarily mediated by modulating the interplay between FXR, NF-κB/TNF-α/IL-6, and Wnt/ß-catenin signaling pathways.

Experienced Love: An Empirical Account.

This article presents new evidence on the prevalence, dynamics, and hedonic correlates of experienced love from data describing the emotion, well-being, and time use of a diverse sample of 3,867 U.S. adults every half hour for 10 days (N = 1.12 million) supplemented by a hedonic snapshot of an additional 7,255 adults. The findings allude to the seemingly functional and adaptive nature of love and to similarities across binary gender-men and women reported comparable degrees of (passionate) partner love overall, elevated partner love after prolonged same-day separations, substantially elevated well-being in love's presence, and reduced (but not extinguished) partner love in mature marital cohorts. The gender differences that were found-women reported more child love than men, and men exhibited a less pronounced reduction in partner love across cohorts-are also consistent with functional accounts of love that recognize the varying role of men and women in the formation and sustenance of relationships.

Variety Is the Spice of Life: Diverse Social Networks Are Associated With Social Cohesion and Well-Being.

Both homophily and heterophily are observed in humans. Homophily reinforces homogeneous social networks, and heterophily creates new experiences and collaborations. However, at the extremes, high levels of homophily can cultivate prejudice toward out-groups, whereas high levels of heterophily can weaken in-group support. Using data from 24,726 adults (M = 46 years; selected from 10,398 English neighborhoods) and the composition of their social networks based on age, ethnicity, income, and education, we tested the hypothesis that a middle ground between homophily and heterophily could be the most beneficial for individuals. We found that network homophily, mediated by perceived social cohesion, is associated with higher levels of subjective well-being but that there are diminishing returns, because at a certain point increasing network homophily is associated with lower social cohesion and, in turn, lower subjective well-being. Our results suggest that building diverse social networks provides benefits that cannot be attained by homogeneous networks.

Misplaced Divides? Discussing Political Disagreement With Strangers Can Be Unexpectedly Positive.

Differences of opinion between people are common in everyday life, but discussing those differences openly in conversation may be unnecessarily rare. We report three experiments (N = 1,264 U.S.-based adults) demonstrating that people's interest in discussing important but potentially divisive topics is guided by their expectations about how positively the conversation will unfold, leaving them more interested in having a conversation with someone who agrees versus disagrees with them. People's expectations about their conversations, however, were systematically miscalibrated such that people underestimated how positive these conversations would be-especially in cases of disagreement. Miscalibrated expectations stemmed from underestimating the degree of common ground that would emerge in conversation and from failing to appreciate the power of social forces in conversation that create social connection. Misunderstanding the outcomes of conversation could lead people to avoid discussing disagreements more often, creating a misplaced barrier to learning, social connection, free inquiry, and free expression.