Relationships among age, motivation, and exercise among women Veterans.

Physical activity (PA) and exercise are central to maintaining health, however research has shown steep declines in PA and exercise among women Veterans as they age. Though motivation may be an important contributor to initiating and sustaining exercise that may change across the lifespan, little is known about exercise motivation and its relation to age and exercise behavior among women Veterans. This cross-sectional study sought to describe exercise motivations, examine relationships among exercise motivations and age, and explore the degree to which age and motivation predict self-reported exercise behavior among women Veterans. We conducted a secondary data analysis from a regional mail survey of 197 women Veterans (mean age = 51; SD = 10.5) enrolled in Veterans Health Administration primary care in a northeastern region (N = 180 in analysis). Measures included demographics (age, body mass index), self-reported exercise motivation, and an estimate of average weekly exercise. Participants endorsed multiple motivators for exercise, most prominently fitness and health management. Age was significantly negatively related to amount of exercise and with socializing as an exercise motivation. After accounting for body mass index, age was a significant predictor of exercise behavior, and exercise motivations accounted for an additional 7.3% of variance in self-reported weekly exercise. Our results suggest that although motivation is a potentially important predictor of exercise, factors beyond motivation may better predict exercise in women Veterans. Further research is needed on personal and practical facilitators and barriers to exercise in this population.

Non-voltage gated Ca2+ channel signaling in glomerular cells in kidney health and disease.

Positioned at the head of the nephron, the renal corpuscle generates a plasma ultrafiltrate to initiate urine formation. Three major cell types within the renal corpuscle, the glomerular mesangial cells, podocytes, and glomerular capillary endothelial cells communicate via endocrine and paracrine signaling mechanisms to maintain structure and function of the glomerular capillary network and filtration barrier. Ca2+ signaling mediated by several distinct plasma membrane Ca2+ channels modulates the functions of all three cell types. The last two decades have witnessed pivotal advances in understanding of Ca2+ channel function and regulation in glomerular cells, particularly non-voltage gated Ca2+ channels, in health and renal disease. This review summarizes the current knowledge of the physiological and pathological impact of non-voltage gated Ca2+ channel signaling in glomerular capillary endothelium, mesangial cells and podocytes. The main focus is on transient receptor potential and store-operated Ca2+ channels, but ionotropic N-methyl-D-aspartate receptors and purinergic 2X receptors also are discussed. This update of Ca2+ channel functions in the renal corpuscle and their cellular signaling cascades is intended to inform development of therapeutic strategies targeting these channels to treat kidney diseases, particularly diabetic nephropathy.

Brief modular anxiety intervention for primary care: Hybrid I pilot randomized controlled trial of feasibility, acceptability, effectiveness, and implementation potential.

BACKGROUND: Anxiety is highly prevalent, but undertreated, in primary care. Brief, non-pharmacological interventions are needed. Modular Anxiety Skills Training (MAST), a cognitive-behavioral anxiety intervention, was developed for primary care and tailored for a Veteran sample (MAST-V). The purpose of this mixed methods pilot study was to evaluate MAST-V's feasibility, acceptability, and implementation potential, and preliminarily examine its effectiveness compared to Primary Care Behavioral Health (PCBH) usual care. METHODS: This hybrid I randomized controlled trial (conducted 2019-2021) assigned 35 primary care patients (Mage = 47, 17 % female, 27 % racial/ethnic minority) with clinically significant anxiety symptoms to receive MAST-V or PCBH usual care. Participants completed validated measures of anxiety symptoms and functional impairment at 0, 4, 8, 12, and 16 weeks. RESULTS: Participants attended more sessions in MAST-V than usual care. After necessary adjustments to reduce session duration, MAST-V will likely fit within PCBH practice parameters. Participants in both conditions valued treatment, but treatment satisfaction, credibility, and therapeutic alliance were higher for MAST-V. Study therapists achieved high treatment fidelity and rated MAST-V as highly feasible, acceptable, and appropriate for PCBH. They identified ways to address potential barriers to implementation. MAST-V was more effective than usual care in reducing anxiety symptoms and impairment. LIMITATIONS: This was a small pilot study at a single site using study therapists. Results should be considered preliminary until replicated in a full-scale clinical trial. CONCLUSIONS: This brief modular anxiety intervention, which was designed with implementation in mind, may help to address the anxiety treatment gap in primary care.

House Dust-Derived Mixtures of Organophosphate Esters Alter the Phenotype, Function, Transcriptome, and Lipidome of KGN Human Ovarian Granulosa Cells.

Organophosphate esters (OPEs), used as flame retardants and plasticizers, are present ubiquitously in the environment. Previous studies suggest that exposure to OPEs is detrimental to female fertility in humans. However, no experimental information is available on the effects of OPE mixtures on ovarian granulosa cells, which play essential roles in female reproduction. We used high-content imaging to investigate the effects of environmentally relevant OPE mixtures on KGN human granulosa cell phenotypes. Perturbations to steroidogenesis were assessed using ELISA and qRT-PCR. A high-throughput transcriptomic approach, TempO-Seq™, was used to identify transcriptional changes in a targeted panel of genes. Effects on lipid homeostasis were explored using a cholesterol assay and global lipidomic profiling. OPE mixtures altered multiple phenotypic features of KGN cells, with triaryl OPEs in the mixture showing higher potencies than other mixture components. The mixtures increased basal production of steroid hormones; this was mediated by significant changes in the expression of critical transcripts involved in steroidogenesis. Further, the total-OPE mixture disrupted cholesterol homeostasis and the composition of intracellular lipid droplets. Exposure to complex mixtures of OPEs, similar to those found in house dust, may adversely affect female reproductive health by altering a multitude of phenotypic and functional endpoints in granulosa cells. This study provides novel insights into the mechanisms of actions underlying the toxicity induced by OPEs and highlights the need to examine the effects of human relevant chemical mixtures.

Examining animal testing for risk assessment: A WC-12 workshop report.

In toxicology and regulatory testing, the use of animal methods has been both a cornerstone and a subject of intense debate. To continue this discourse a panel and audience representing scientists from various sectors and countries convened at a workshop held during the 12th World Congress on Alternatives and Animal Use in the Life Sciences (WC-12). The ensuing discussion focused on the scientific and ethical considerations surrounding the necessity and responsibility of defending the creation of new animal data in regulatory testing. The primary aim was to foster an open dialogue between the panel members and the audience while encouraging diverse perspectives on the responsibilities and obligations of various stakeholders (including industry, regulatory bodies, technology developers, research scientists, and animal welfare NGOs) in defending the development and subsequent utilization of new animal data. This workshop summary report captures the key elements from this critical dialogue and collective introspection. It describes the intersection of scientific progress and ethical responsibility as all sectors seek to accelerate the pace of 21st century predictive toxicology and new approach methodologies (NAMs) for the protection of human health and the environment.

Niche construction and the environmental term of the price equation: How natural selection changes when organisms alter their environments.

Organisms construct their own environments and phenotypes through the adaptive processes of habitat choice, habitat construction, and phenotypic plasticity. We examine how these processes affect the dynamics of mean fitness change through the environmental change term of the Price Equation. This tends to be ignored in evolutionary theory, owing to the emphasis on the first term describing the effect of natural selection on mean fitness (the additive genetic variance for fitness of Fisher's Fundamental Theorem). Using population genetic models and the Price Equation, we show how adaptive niche constructing traits favorably alter the distribution of environments that organisms encounter and thereby increase population mean fitness. Because niche-constructing traits increase the frequency of higher-fitness environments, selection favors their evolution. Furthermore, their alteration of the actual or experienced environmental distribution creates selective feedback between niche constructing traits and other traits, especially those with genotype-by-environment interaction for fitness. By altering the distribution of experienced environments, niche constructing traits can increase the additive genetic variance for such traits. This effect accelerates the process of overall adaption to the niche-constructed environmental distribution and can contribute to the rapid refinement of alternative phenotypic adaptations to different environments. Our findings suggest that evolutionary biologists revisit and reevaluate the environmental term of the Price Equation: owing to adaptive niche construction, it contributes directly to positive change in mean fitness; its magnitude can be comparable to that of natural selection; and, when there is fitness G × E, it increases the additive genetic variance for fitness, the much-celebrated first term.

Treatment of posttraumatic stress disorder with prolonged exposure for primary care (PE-PC): Effectiveness and patient and therapist factors related to symptom change and retention.

Prolonged exposure (PE) is a first-line treatment for posttraumatic stress disorder (PTSD) available in specialty mental health. PE for primary care (PE-PC) is a brief version of PE adapted for primary care mental health integration, composed of four-eight, 30-min sessions. Using retrospective data of PE-PC training cases from 155 Veterans Health Administration (VHA) providers in 99 VHA clinics who participated in a 4- to 6-month PE-PC training and consultation program, we examined patients' PTSD and depression severity across sessions via mixed effects multilevel linear modeling. Additionally, hierarchical logistic regression analysis was conducted to assess predictors of treatment dropout. Among 737 veterans, medium-to-large reductions in PTSD (intent-to-treat, Cohen's d = 0.63; completers, Cohen's d = 0.79) and small-to-medium reductions in depression (intent-to-treat, Cohen's d = 0.40; completers, Cohen's d = 0.51) were observed. The modal number of PE-PC sessions was five (SD = 1.98). Providers previously trained in both PE and cognitive processing therapy (CPT) were more likely than providers who were not trained in either PE or CPT to have veterans complete PE-PC (OR = 1.54). Veterans with military sexual trauma were less likely to complete PE-PC than veterans with combat trauma (OR = 0.42). Asian American and Pacific Islander veterans were more likely than White veterans to complete treatment (OR = 2.93). Older veterans were more likely than younger veterans to complete treatment (OR = 1.11). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Relative rates of evolution of male-beneficial nuclear compensatory mutations and male-harming Mother's Curse mitochondrial alleles.

Mother's Curse alleles represent a significant source of potential male fitness defects. The maternal inheritance of mutations with the pattern of sex-specific fitness effects, s♀>0>s♂, allows Mother's Curse alleles to spread through a population even though they reduce male fitness. Although the mitochondrial genomes of animals contain only a handful of protein-coding genes, mutations in many of these genes have been shown to have a direct effect on male fertility. The evolutionary process of nuclear compensation is hypothesized to counteract the male-limited mitochondrial defects that spread via Mother's Curse. Here we use population genetic models to investigate the evolution of compensatory autosomal nuclear mutations that act to restore the loss of fitness caused by mitochondrial mutation pressures. We derive the rate of male fitness deterioration by Mother's Curse and the rate of restoration by nuclear compensatory evolution. We find that the rate of nuclear gene compensation is many times slower than that of its deterioration by cytoplasmic mutation pressure, resulting in a significant lag in the recovery of male fitness. Thus, the numbers of nuclear genes capable of restoring male mitochondrial fitness defects must be large in order to sustain male fitness in the face of mutation pressures.

Maternal inheritance, such as that of the mitochondrial genome, allows genetic variants that benefit female survival and reproduction to spread even when they negatively impact male fitness, referred to as Mother's Curse alleles. The maintenance of male fitness in spite of such alleles is predominantly attributed to the spread of variants in the nuclear genome that compensate for the male harming effects. However, the relative rate of nuclear compensatory evolution has not been derived. Here we show that many features of nuclear compensatory mutations slow their rate of evolution many-fold relative to the rapid spread of Mother's Curse alleles. Thus, the pool of nuclear genes capable of compensating for mitochondria-associated male harm must be very large to maintain male fitness, especially in light of the potential contribution of male-harming effects from the maternally inherited microbiome.

Health service utilization among women veterans who report eating disorder symptoms.

OBJECTIVE: Describe health service utilization in women veterans with eating disorder symptoms and characterize the nature of mental health services received. METHOD: Women veterans (N = 191) in a northeastern Veterans Health Administration region completed the Eating Disorders Examination Questionnaire. Health service utilization was then observed for 5 years across multiple domains (i.e., mental health, primary care, telephone consultations, emergency services); negative binomial or zero-inflated negative binomial regression models (mental health) estimated the relative impact of reported eating disorder symptoms on health service utilization. RESULTS: After adjusting for the effects of age and body mass index, higher eating disorder symptoms were associated with higher primary care, mental health services, and telephone consultations. Eating disorder diagnoses were infrequent across the sample. DISCUSSION: Women veterans with higher self-reported eating disorder symptoms evidence higher health service utilization across common healthcare domains. Encounter data suggest that eating disorder symptoms are rarely identified or clinically addressed by providers. Existing mental health visits may represent an opportunity for selective screening for eating disorder symptoms, particularly among women who evidence known risk factors. PUBLIC SIGNIFICANCE: This study reveals that women veterans with higher levels of eating disorder symptoms (e.g., dietary restriction, poor body image) use more primary care, mental health, and telephone consultations than others, but may not receive services that target disordered eating. Opportunities may exist to better identify eating disorder symptoms in the context of existing mental health visits, or potentially to combine treatment for eating disorder symptoms into their mental health care.

Effects of the pesticide deltamethrin on high fat diet-induced obesity and insulin resistance in male mice.

Worldwide, rates of metabolic diseases are rapidly increasing and environmental exposure to pesticides, pollutants and/or other chemicals may play a role. Reductions in Brown Adipose Tissue (BAT) thermogenesis, mediated in part by uncoupling protein 1 (Ucp1), are associated with metabolic diseases. In the current study, we investigated whether the pesticide deltamethrin (0.01-1 mg/kg bw/day) incorporated into a high-fat diet and fed to mice housed at either room temperature (21°C) or thermoneutrality (29°C) would suppress BAT activity and accelerate the development of metabolic disease. Importantly, thermoneutrality allows for more accurate modeling of human metabolic disease. We found that, 0.01 mg/kg bw/day of deltamethrin induced weight loss, improved insulin sensitivity and increased energy expenditure, effects that were associated with increases in physical activity. In contrast, exposure to 0.1 and 1 mg/kg bw/day deltamethrin had no effect on any of the parameters examined. Deltamethrin treatment in mice did not alter molecular markers of BAT thermogenesis, despite observing suppression of UCP1 expression in cultured brown adipocytes. These data indicate that while deltamethrin inhibits UCP1 expression in vitro, 16wks exposure does not alter BAT thermogenesis markers nor exacerbates the development of obesity and insulin resistance in mice.

A Randomized Clinical Trial of Clinician-Supported PTSD Coach in VA Primary Care Patients.

BACKGROUND: Posttraumatic stress disorder (PTSD) is common in primary care patients; however, evidence-based treatments are typically only available in specialty mental healthcare settings and often not accessed. OBJECTIVE: To test the effectiveness of a brief primary care-based treatment, Clinician-Supported PTSD Coach (CS PTSD Coach) was compared with Primary Care Mental Health Integration-Treatment as Usual (PCMHI-TAU) in (1) reducing PTSD severity, (2) engaging veterans in specialty mental health care, and (3) patient satisfaction with care. DESIGN: Multi-site randomized pragmatic clinical trial. PARTICIPANTS: A total of 234 veterans with PTSD symptoms who were not currently accessing PTSD treatment. INTERVENTION: CS PTSD Coach was designed to be implemented in Veterans Affairs PCMHI and combines mental health clinician support with the "PTSD Coach" mobile app. Four 30-min sessions encourage daily use of symptom management strategies. MAIN MEASURES: PTSD severity was measured by clinician-rated interviews pre- and post-treatment (8 weeks). Self-report measures assessed PTSD, depression, and quality of life at pretreatment, posttreatment, and 16- and 24-week follow-ups, and patient satisfaction at post-treatment. Mental healthcare utilization was extracted from medical records. KEY RESULTS: Clinician-rated PTSD severity did not differ by condition at post-treatment. CS PTSD Coach participants improved more on patient-reported PTSD severity at post-treatment than TAU participants (D = .28, p = .021). Coach participants who continued to have problematic PTSD symptoms at post-treatment were not more likely to engage in 2 sessions of specialty mental health treatment than TAU participants. Coach participants engaged in 74% more sessions in the intervention and reported higher treatment satisfaction than TAU participants (p < .001). CONCLUSIONS: A structured 4-session intervention designed to align with patient preferences for care resulted in more patient-reported PTSD symptom relief, greater utilization of mental health treatment, and overall treatment satisfaction than TAU, but not more clinician-rated PTSD symptom relief or engagement in specialty mental health.

Feasibility and acceptability of a brief intervention to improve mild traumatic brain injury recovery: Problem-solving training-concussion.

OBJECTIVE: Mild traumatic brain injuries (mTBIs) are common among Veterans. Although the majority of neurobehavioral symptoms resolve following mTBI, studies with Veteran samples demonstrate a high frequency and chronicity of neurobehavioral complaints (e.g., difficulties with attention, frustration tolerance) often attributed to mTBI. Recent opinions suggest the primacy of mental health treatment, and existing mTBI practice guidelines promote patient-centered intervention beginning in primary care (PC). However, trial evidence regarding effective clinical management in PC is lacking. This study evaluated the feasibility and acceptability of a brief, PC-based problem-solving intervention to reduce psychological distress and neurobehavioral complaints. RESEARCH METHOD/DESIGN: Mixed method open clinical trial of 12 combat Veterans with a history of mTBI, chronic neurobehavioral complaints, and psychological distress. Measures included qualitative and quantitative indicators of feasibility (recruitment and retention metrics, interview feedback), patient acceptability (treatment satisfaction, perceived effectiveness), and change in psychological distress as measured by the Brief Symptom Inventory-18. RESULTS: The protocol was successfully delivered via in-person and telehealth treatment modalities (4.3 sessions attended on average; 58% completed the full protocol). Patient interview data suggested that treatment content was personally relevant, and patients were satisfied with their experience. Treatment completers described the intervention as helpful and reported corresponding reductions in psychological distress (ES = 1.8). Dropout was influenced by the onset of the COVID-19 pandemic. CONCLUSIONS/IMPLICATIONS: Further study with a more diverse, randomized sample is warranted. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The effects of cognitive impairment on the multi-scale dynamics of standing postural control during visual-search in older men.

Background: Cognitive impairment disrupts postural control, particularly when standing while performing an unrelated cognitive task (i.e., dual-tasking). The temporal dynamics of standing postural sway are "complex," and such complexity may reflect the capacity of the postural control system to adapt to task demands. We aimed to characterize the impact of cognitive impairment on such sway complexity in older adults. Methods: Forty-nine older adult males (Alzheimer's disease (AD): n = 21; mild cognitive impairment (MCI): n = 13; cognitively-intact: n = 15) completed two 60-s standing trials in each of single-task and visual-search dual-task conditions. In the dual-task condition, participants were instructed to count the frequency of a designated letter in a block of letters projected on screen. The sway complexity of center-of-pressure fluctuations in anterior-posterior (AP) and medial-lateral (ML) direction was quantified using multiscale entropy. The dual-task cost to complexity was obtained by calculating the percent change of complexity from single- to dual-task condition. Results: Repeated-measures ANOVAs revealed significant main effects of group (F > 4.8, p < 0.01) and condition (F = 7.7, p < 0.007) on both AP and ML sway complexity; and significant interaction between group and condition for ML sway complexity (F = 3.7, p = 0.03). The AD group had the lowest dual-task ML complexity, as well as greater dual-task cost to ML (p = 0.03) compared to the other two groups. Visual-search task accuracy was correlated with ML sway complexity in the dual-task condition (r = 0.42, p = 0.007), and the dual-task cost to ML sway complexity (r = 0.39, p = 0.01) across all participants. Conclusion: AD-related cognitive impairment was associated with a greater relative reduction in postural sway complexity from single- to dual-tasking. Sway complexity appears to be sensitive to the impact of cognitive impairment on standing postural control.

Microplastics exposure: implications for human fertility, pregnancy and child health.

Plastics found in our everyday environment are becoming an increasing concern for individual and population-level health, and the extent of exposure and potential toxic effects of these contaminants on numerous human organ systems are becoming clear. Microplastics (MPs), tiny plastic particles, appear to have many of the same biological effects as their plastic precursors and have the compounded effect of potential accumulation in different organs. Recently, microplastic accumulation was observed in the human placenta, raising important questions related to the biological effects of these contaminants on the health of pregnancies and offspring. These concerns are particularly heightened considering the developmental origins of health and disease (DOHaD) framework, which postulates that in utero exposure can programme the lifelong health of the offspring. The current review examines the state of knowledge on this topic and highlights important avenues for future investigation.

Chronic exposure to synthetic food colorant Allura Red AC promotes susceptibility to experimental colitis via intestinal serotonin in mice.

Chemicals in food are widely used leading to significant human exposure. Allura Red AC (AR) is a highly common synthetic colorant; however, little is known about its impact on colitis. Here, we show chronic exposure of AR at a dose found in commonly consumed dietary products exacerbates experimental models of colitis in mice. While intermittent exposure is more akin to a typical human exposure, intermittent exposure to AR in mice for 12 weeks, does not influence susceptibility to colitis. However, exposure to AR during early life primes mice to heightened susceptibility to colitis. In addition, chronic exposure to AR induces mild colitis, which is associated with elevated colonic serotonin (5-hydroxytryptamine; 5-HT) levels and impairment of the epithelial barrier function via myosin light chain kinase (MLCK). Importantly, chronic exposure to AR does not influence colitis susceptibility in mice lacking tryptophan hydroxylase 1 (TPH1), the rate limiting enzyme for 5-HT biosynthesis. Cecal transfer of the perturbed gut microbiota by AR exposure worsens colitis severity in the recipient germ-free (GF) mice. Furthermore, chronic AR exposure elevates colonic 5-HT levels in naïve GF mice. Though it remains unknown whether AR has similar effects in humans, our study reveals that chronic long-term exposure to a common synthetic colorant promotes experimental colitis via colonic 5-HT in gut microbiota-dependent and -independent pathway in mice.

Randomized Clinical Trial of Brief Primary Care-Based Mindfulness Training Versus a Psychoeducational Group for Veterans With Posttraumatic Stress Disorder.

Objective: Individuals with posttraumatic stress disorder (PTSD) symptoms are often reluctant to engage in traditional mental health care but do seek primary care services. Alternative strategies are needed to develop emotional regulation skills among individuals with PTSD symptoms. This study examined the feasibility and effectiveness of Primary Care Brief Mindfulness Training (PCBMT) compared to a psychoeducational group for reducing PTSD symptoms.Methods: Primary care patients (n = 55) with DSM-5 PTSD symptoms but not engaged in PTSD psychotherapies were randomized to 4-week PCBMT or a PTSD psychoeducation group (EDU). Both groups were cofacilitated by mental health providers and veteran peer specialists. Between January 2019 and March 2020, assessments were completed at baseline, post-treatment, and 16- and 24-week follow-up.Results: PCBMT participants had significantly larger decreases in PTSD symptoms from pre- to post-treatment (d = 0.57) and depression from pre-treatment to 16- and 24-week follow-ups (d = 0.67, 0.60) compared to EDU. PCBMT participants also reported significantly greater improvements in health responsibility (d = 0.79), stress management (d = 0.99), and not feeling dominated by symptoms (d = 0.71). Both interventions resulted in the majority of participants "stepping up" to a higher level of PTSD care.Conclusions: Brief mindfulness training is effective for reducing psychiatric symptoms and improving broader recovery outcomes and health promoting behaviors. For individuals who are not yet willing to engage in trauma-focused PTSD treatment, PCBMT may be preferable and more effective than psychoeducational classes as preliminary treatments. Further research is needed to confirm the effectiveness of PCBMT in a larger sample and investigate factors that will support wider implementation in primary care settings.Clinical Trials Registration: ClinicalTrials.gov identifier: NCT03352011.

Non-surgical management for air injection injury to the hand, a case report.

We present a case a high pressure air injection injury to the index finger with air extension proximal to the elbow. This patient was treated non-surgically with close observation. At 3 year follow-up, no lasting deficits or complications were noted and radiographs revealed complete resolution of the air tissue dissection.

Host-parasite coevolution: Partitioning the effects of natural selection and environmental change using coupled Price equations.

George Price showed how the effects of natural selection and environmental change could be mathematically partitioned. This partitioning may be especially useful for understanding host-parasite coevolution, where each species represents the environment for the other species. Here, we use coupled Price equations to study this kind of antagonistic coevolution. We made the common assumption that parasites must genetically match their host's genotype to avoid detection by the host's self/nonself recognition system, but we allowed for the possibility that non-matching parasites have some fitness. Our results show how natural selection on one species results in environmental change for the other species. Numerical iterations of the model show that these environmental changes can periodically exceed the changes in mean fitness due to natural selection, as suggested by R.A. Fisher. Taken together, the results give an algebraic dissection of the eco-evolutionary feedbacks created during host-parasite coevolution.

Niche construction in quantitative traits: heritability and response to selection.

A central tenet of niche construction (NC) theory is that organisms can alter their environments in heritable and evolutionarily important ways, often altering selection pressures. We suggest that the physical changes niche constructors make to their environments may also alter trait heritability and the response of phenotypes to selection. This effect might change evolution, over and above the effect of NC acting via selection alone. We develop models of trait evolution that allow us to partition the effects of NC on trait heritability from those on selection to better investigate their distinct effects. We show that the response of a phenotype to selection and so the pace of phenotypic change can be considerably altered in the presence of NC and that this effect is compounded when trans-generational interactions are included. We argue that novel mathematical approaches are needed to describe the simultaneous effects of NC on trait evolution via selection and heritability. Just as indirect genetic effects have been shown to significantly increase trait heritability, the effects of NC on heritability in our model suggest a need for further theoretical development of the concept of heritability.